cancer biomarkers guide

Cancer biomarkers guide: breast, lung, and colorectal cancer

Find the right cancer biomarker for your research using our cancer immunohistochemistry (IHC) guide to breast, lung, and colorectal cancer.

IHC is a hugely popular tool for both cancer research and the clinical diagnosis of different cancer types. Every cancer type, including lung, breast, and colorectal cancer, will express its own cancer-specific protein signal. Using IHC to detect this signal is a powerful tool used in clinical diagnostic tests.

IHC tests can be run quickly, with ease and at a low cost compared to competing diagnostic tests. It is a robust and reliable test and, with a good panel of specific biomarkers, it is ideal for rapid clinical diagnosis.

Choosing an antibody for IHC

Regardless of which cancer type you are researching, a sensitive, specific and consistent antibody is required as a good starting point. Antibody validation is key to ensuring antibody specificity. We use a variety of experimental applications to validate our antibodies including IHC and many of the antibodies on our catalog will state that they are suitable for use in IHC. You can also find out more about our antibody validation methods, here.

To get consistency between your IHC experiments we recommend using an antibody generated using recombinant technology (ie recombinant antibodies). These antibodies are developed in vitro and do not rely on an animal’s immune system for generation making them more consistent, batch-to-batch. You can find out more about the benefits of recombinant antibodies, here.

In this guide, we are focusing on three primary cancer types; breast, lung, and colorectal cancer. Here you will be able to find the right biomarker for your research and select the most highly recommended antibody for use in IHC. 

Find biomarkers for different cancer types

Primary IHC markers
Estrogen receptor alpha
Determining the distribution of estrogen receptor alpha (ER-α) in breast cancer samples is an important initial step for the diagnosis and treatment evaluation of the disease (Hicks et al., 2017). Approximately 70% of breast cancer samples will give a positive staining signal for ER-α making it a crucial biomarker for breast cancer diagnosis (Jeselsohn et al., 2015). ER-α is a nuclear protein with a ligand-dependent transcription factor function. It is also most commonly detected in both luminal A and B subtypes of breast cancer (Jeselsohn et al., 2015).
IHC stain: nuclear signal
Recommended IHC antibody: Recombinant Anti-Estrogen Receptor alpha antibody [EPR4097] - ChIP Grade (ab108398)
Progesterone receptor
The progesterone receptor (PR) is another biomarker important for the initial diagnosis and evaluation of breast cancer (Hicks et al., 2017). PR is known to be induced by ER-α and plays a key role in ER-α protein regulation. PGR as a biomarker is therefore commonly used as an indicator of ER-α function (Mohammed et al., 2015). PR is highly expressed in luminal A-type breast cancer tissue and is associated with a good prognosis (Lim et al., 2016). 
IHC stain: nuclear signal
Recommended IHC antibody: Recombinant Anti-Progesterone Receptor antibody [YR85] (ab32085)
ErbB2/HER2
Overexpression of ErbB2/HER2 can be found in 20–30% of breast cancer tumors and is commonly found in more aggressive types of the disease (Mitri et al., 2012). ErbB2/HER2 is used as a diagnostic indicator for the FDA approved monoclonal antibody therapy, Trastuzumab (Herceptin). During this therapy ErbB2/HER2 acts as the binding target of Trastuzumab (Piccart-Gebhart et al., 2006). 
IHC stain: cytoplasmic, nuclear, and strongly in the cell membrane
Recommended IHC antibody: Recombinant Anti-ErbB 2 antibody [SP3] (ab16662)
p53
Mutated versions of the tumor suppressor p53 can be found in 80% of triple-negative breast cancer (TNBC) cases, ie tumors lacking expression of ER, PR, and ErbB2/HER2 (Duffy et al., 2018). This makes mutant p53 an excellent biomarker for TNBC, one of the more difficult breast cancers to treat as it will not respond to endocrine or anti-HER2 treatments (Li et al., 2019). Currently, there are mixed findings on the prognostic potential of p53 expression in breast cancer. Some studies have associated it with a positive prognostic outcome and others negative. (Li et al., 2019). p53 IHC stains are commonly used for diagnostic purposes.
IHC stain: cytoplasm and strong nuclear
Recommended IHC antibody: Anti-p53 antibody [DO-1] - ChIP Grade (ab1101)
BRCA1
Mutations in the BRCA genes are some of the most well-known breast cancer-associated protein mutations. BRCA1 is a tumor suppressor gene and one of the most commonly mutated genes in breast cancer. Patients with a BRCA1 mutation have a 40–80% increased risk of developing the disease making it a crucial biomarker in the diagnosis and prognosis of many breast cancer types (Fackenthal et al., 2007). 
IHC stain: nuclear signal
Recommended IHC antibody: Anti-BRCA1 antibody [MS110] (ab16780)
Epidermal growth factor receptor (EGFR)
EGFR is a transmembrane receptor and its expression is frequently found in TNBC and inflammatory breast cancer (IBC). It is most commonly associated with a poor prognosis (Masuda et al., 2012). High levels of EGFR expression is linked to an increased ability of the breast cancer to undergo metastasis making it a common biomarker for aggressive breast cancer types (Ali et al., 2016).  
IHC stain: cytoplasm and strong nuclear
Recommended IHC antibody: Anti-EGFR antibody [EP38Y] (ab52894)
CK20 (Cytokeratin 20) and CK7 (Cytokeratin 7)
CK7 and CK20 are cytokeratins expressed in the breast epithelia. Different CK7 and CK20 IHC expression patterns are commonly used to distinguish many carcinoma types including breast carcinomas. Most breast cancers are CK7 positive and CK20 negative, making the combination of these cytokeratins an excellent biomarker combination. Approximately 80% of breast adenocarcinomas are CK7 positive and CK20 negative (Chu et al., 2000). 
IHC stain: cytoplasm 
Recommended CK20 IHC antibody: Recombinant Anti-Cytokeratin 20 antibody [EPR1622Y] - Cytoskeleton Marker (ab76126) 
Recommended CK7 IHC antibody: Recombinant Anti-Cytokeratin 7 antibody [EPR1619Y] - Cytoskeleton Marker (ab68459)
APOBEC3B (apolipoprotein B mRNA editing catalytic polypeptide-like 3B)
APOBEC3B is expressed in ER-positive breast cancers and is used as a biomarker of poor prognosis for the disease and is a driver for downstream genetic mutations which accelerate the progression of breast cancer. These mutations make APOBEC3B positive breast cancers extremely drug-resistant (Zou et al., 2017). 
IHC stain: nuclear signal
Recommended IHC antibody: Anti-APOBEC3B antibody - N-terminal (ab191695)
Cell type-specific markers
FOXA1
The transcription factor FOXA1 has been shown to have a unique distribution within breast cancer cells compared to other cell types. FOXA1 binding is crucial for chromatin opening and the transcriptional activation of ER-α responsive genes within breast cancer cells (Cowper-Sallari et al., 2012). Studies have identified thousands of breast cancer-associated single nucleotide polymorphisms (SNPs) within the enhancer regions for FOXA1 (Meyer et al., 2012). 
IHC stain: nuclear signal
Recommended IHC antibody: Recombinant Anti-FOXA1 antibody [EPR10881] (ab170933)
GATA-binding protein 3 (GATA3)
GATA3 is a zinc finger transcription factor crucial for breast luminal epithelium differentiation. It is also a diagnostic biomarker for both primary and metastatic breast cancer and commonly found in luminal A and B breast cancer tissue. GATA3 also has a strong association with HER2 positive and ER- α positive hormone response in luminal breast cancers (Shaoxian et al., 2017). 
IHC stain: nuclear signal
Recommended IHC antibody: Recombinant Anti-GATA3 antibody [EPR16651] - ChIP Grade (ab199428)
CK5 (Cytokeratin 5)
CK5 is a cytokine found to be expressed in the basal cell layer of the mammary duct. Tumors that arise from these cells are also known to be CK5 positive and so CK5 is an excellent biomarker for the diagnosis of basal type breast cancers. The CK5 positive progenitor cells may also differentiate into glandular and myoepithelial cancer types (Laakso et al., 2005).  
IHC stain: cytoplasm and cell membrane
Recommended IHC antibody: Recombinant Anti-Cytokeratin 5 antibody [EP1601Y] - Cytoskeleton Marker (ab52635)
Smooth muscle myosin heavy chain (SMMHC)
SMMHC is expressed specifically in the contractile myoepithelial cells of the breast. A loss of the myoepithelial layer is commonly associated with invasive breast cancers. Markers such as SMMHC can be used in IHC to detect this layer more reliably than a hematoxylin and eosin stain alone (Zaha et al., 2014). 
IHC stain: cytoplasm
Recommended IHC antibody: Recombinant Anti-smooth muscle Myosin heavy chain 11 antibody [EPR5336(B)] (ab133567)
E-cadherin
E-cadherin is expressed at the cell junction of normal breast epithelial cells. A loss of E-cadherin is associated with a phenotypic switch by these cells to become invasive and migratory breast cancer cells. Loss of E-cadherin expression is commonly used as a biomarker for metastatic lobular breast carcinomas (Singhai et al., 2011).
IHC stain: Cell junctions
Recommended IHC antibody: Recombinant Anti-E Cadherin antibody [EP700Y] - Intercellular Junction Marker (ab40772)
Alpha smooth muscle actin (ACTA2)
Smooth muscle actin is highly expressed in normal breast myoepithelial cells. It is commonly used as a marker of this normal breast cell type. Smooth muscle actin is commonly used for histology in conjunction with SMMHC and calponins to mark out the myoepithelial layer. A combination of markers such as this is much more reliable than using hematoxylin and eosin stains alone (Zaha et al., 2014).
IHC stain: cytoplasm
Recommended IHC antibody: Anti-alpha smooth muscle Actin antibody (ab5694)
Calponin 
Calponins are proteins found within the contractile components of the myoepithelium. Similarly to SMMHC and ACTA2, calponin stains are used as a marker of the myoepithelial layer in the diagnosis of invasive breast cancers (Zaha et al., 2014). 
IHC stain: cytoplasm
Recommended IHC antibody: Recombinant Anti-Calponin 1 antibody [EP798Y] (ab46794), Anti-Calponin 2 antibody (ab129331), Anti-Calponin 3 antibody (ab151427)
Delta-1-Catenin 
Delta-1-Catenin is a member of the p120 family and acts as a binder of E-cadherin. Delta-1-Catenin can be used in histology to detect invasive lobular breast cancer, high tumor-node-metastasis stage, and lymph node metastasis. It is also strongly associated with HER2 positive breast cancers and can be used as an indicator of poor prognosis as it is thought to promote a malignant phenotype (Zhang et al., 2015). 
IHC stain: cytoplasm and cell membrane
Recommended IHC antibody: Recombinant Anti-delta 1 Catenin/CAS antibody [EPR357(2)] (ab92514)
CK14 (Cytokeratin 14)
CK14 is a cytokine found to be expressed in the basal cell layer of the mammary duct. It is most commonly found to be co-expressing with CK5 is this tissue type and similarly to CK5, the histological detection of CK14 is an excellent biomarker for the diagnosis of basal type breast cancers (Laakso et al., 2005).
IHC stain: cytoplasm
Recommended IHC antibody: Recombinant Anti-Cytokeratin 14 antibody [EPR17350] - Cytoskeleton Marker (ab181595)
Other markers
Ki67
Ki67 is an important protein involved in cell division and is commonly used as a marker of cellular proliferation. It is also used in breast cancer diagnosis to determine the level of cell proliferation which can be a prognostic marker and a good indication of well certain breast cancers will respond to endocrine therapy (Niazi et al., 2018). 
IHC stain: nuclear
Recommended IHC antibody: Anti-Ki67 antibody (ab15580)
Cyclin D1
Cyclin D1 is one of the main regulatory proteins of the cell cycle promoting the cell cycle progression from G1 to S phase. Mutations in cyclin D1 are amplified in many different types of cancer including many breast cancers. 50% of breast cancers will contain an overexpression of cyclin D1 (Mohammadizadeh et al., 2013). It has been used as a biomarker for poor prognosis for many breast cancer types, but some studies are beginning to suggest that it could also suggest a positive outcome if expressed in some luminal subtypes of breast cancer (Ortiz et al., 2017). 
IHC stain: nuclear
Recommended IHC antibody: Recombinant Anti-Cyclin D1 antibody [EPR2241] - C-terminal (ab134175)
Cyclooxygenase-2 (COX-2)
COX-2 is an enzyme responsible for producing prostanoids. Its expression in breast tissue correlates strongly with breast cancer development. Overexpression of COX-2 has been shown to drive breast cancer phenotypes and blocking the action of this protein also shows potential for breast cancer therapy. There is also a strong link between COX-2 overexpression in breast adipose tissue and cancer progression linked to obesity (Harris et al., 2014). 
IHC stain: cytoplasm
Recommended IHC antibody: Recombinant Anti-COX2 / Cyclooxygenase 2 antibody [EPR12012] (ab179800)
Caveolin-1
Caveolin-1 is the main component of caveolae, small invaginations found in the cell membrane. It’s also known to play a key role in cell proliferation, invasion, and breast cancer metastasis. It is also used as a biomarker for breast cancer treatments and disease outcome. High expression of caveolin-1 is a sign of poor prognosis an indicates are more aggressive metastatic breast cancer (Qian et al., 2019). 
IHC stain: cell membrane
Recommended IHC antibody: Recombinant Anti-Caveolin-1 antibody [E249] - Caveolae Marker (ab32577)
Peroxisome proliferator-activated receptor (PPAR-γ)
PPAR-γ is a well-studied nuclear hormone receptor. PPAR-γ has been implicated in different types of breast cancer in which its ligands inhibit proliferation and angiogenesis and induce apoptosis (Fenner et al., 2005). It has also been shown to play a role in promoting breast tumor growth through the maintenance of HER2 positive endothelial breast cancer stem cells making its expression a good biomarker for this cell type (Wang et al., 2013). 
IHC stain: nuclear
Recommended IHC antibody: Anti-PPAR gamma antibody - ChIP Grade (ab45036)

​​Breast cancer biomarkers

IHC is an increasingly common method used in the diagnosis of breast cancer and research into breast cancer pathology. There is an increasing number of antibodies available for the detection of breast cancer-specific markers. These markers are used to determine different breast cancer types eg in situ or invasive carcinoma, distinguishing normal breast cell types eg luminal, basal and myoepithelial, and also proliferation and disease progression (Zaha et al., 2014).

Here we look at some of the most common primary IHC markers for breast cancer, some cell type-specific markers, and markers for proliferation and breast cancer progression. We also give our recommended antibody for use in IHC. 

Primary IHC markers

Estrogen receptor alpha

Determining the distribution of estrogen receptor alpha (ER-α) in breast cancer samples is an important initial step for the diagnosis and treatment evaluation of the disease (Hicks et al., 2017). Approximately 70% of breast cancer samples will give a positive staining signal for ER-α making it a crucial biomarker for breast cancer diagnosis (Jeselsohn et al., 2015). ER-α is a nuclear protein with a ligand-dependent transcription factor function. It is also most commonly detected in both luminal A and B subtypes of breast cancer (Jeselsohn et al., 2015).

Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-Estrogen Receptor alpha antibody [EPR4097] - ChIP Grade (ab108398)
Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of human breast ductal infiltrating carcinoma tissue labelling Estrogen Receptor alpha with unpurified ab108398.

IHC stain: nuclear signal
Recommended IHC antibody: Recombinant Anti-Estrogen Receptor alpha antibody [EPR4097] - ChIP Grade (ab108398)


Progesterone receptor

The progesterone receptor (PR) is another biomarker important for the initial diagnosis and evaluation of breast cancer (Hicks et al., 2017). PR is known to be induced by ER-α and plays a key role in ER-α protein regulation. PGR as a biomarker is therefore commonly used as an indicator of ER-α function (Mohammed et al., 2015). PR is highly expressed in luminal A-type breast cancer tissue and is associated with a good prognosis (Lim et al., 2016). 

IHC stain: nuclear signal
Recommended IHC antibody: Recombinant Anti-Progesterone Receptor antibody [YR85] (ab32085)


ErbB2/HER2

Overexpression of ErbB2/HER2 can be found in 20–30% of breast cancer tumors and is commonly found in more aggressive types of the disease (Mitri et al., 2012). ErbB2/HER2 is used as a diagnostic indicator for the FDA approved monoclonal antibody therapy, Trastuzumab (Herceptin). During this therapy ErbB2/HER2 acts as the binding target of Trastuzumab (Piccart-Gebhart et al., 2006). 

Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-ErbB 2 antibody [SP3] (ab16662)
Formalin-fixed, paraffin-embedded human breast, invasive ductal carcinoma tissue stained for ErbB 2 using ab16662 at 1/200 dilution in immunohistochemical analysis, followed by Goat anti Rabbit IgG HRP. Heat mediated antigen retrieval was done using a pH 8.5 buffer.

IHC stain: cytoplasmic, nuclear, and strongly in the cell membrane
Recommended IHC antibody: Recombinant Anti-ErbB 2 antibody [SP3] (ab16662)


p53

Mutated versions of the tumor suppressor p53 can be found in 80% of triple-negative breast cancer (TNBC) cases, ie tumors lacking expression of ER, PR, and ErbB2/HER2 (Duffy et al., 2018). This makes mutant p53 an excellent biomarker for TNBC, one of the more difficult breast cancers to treat as it will not respond to endocrine or anti-HER2 treatments (Li et al., 2019). Currently, there are mixed findings on the prognostic potential of p53 expression in breast cancer. Some studies have associated it with a positive prognostic outcome and others negative. (Li et al., 2019). p53 IHC stains are commonly used for diagnostic purposes.

IHC stain: cytoplasm and strong nuclear
Recommended IHC antibody: ​Anti-p53 antibody [DO-1] - ChIP Grade (ab1101)


BRCA1

Mutations in the BRCA genes are some of the most well-known breast cancer-associated protein mutations. BRCA1 is a tumor suppressor gene and one of the most commonly mutated genes in breast cancer. Patients with a BRCA1 mutation have a 40–80% increased risk of developing the disease making it a crucial biomarker in the diagnosis and prognosis of many breast cancer types (Fackenthal et al., 2007). 

IHC stain: nuclear signal
Recommended IHC antibody: Anti-BRCA1 antibody [MS110] (ab16780)


Epidermal growth factor receptor (EGFR)

EGFR is a transmembrane receptor and its expression is frequently found in TNBC and inflammatory breast cancer (IBC). It is most commonly associated with a poor prognosis (Masuda et al., 2012). High levels of EGFR expression is linked to an increased ability of the breast cancer to undergo metastasis making it a common biomarker for aggressive breast cancer types (Ali et al., 2016).  

IHC stain: cytoplasm and strong nuclear
Recommended IHC antibody: Anti-EGFR antibody [EP38Y] (ab52894)


CK20 (cytokeratin 20) and CK7 (Cytokeratin 7)

CK7 and CK20 are cytokeratins expressed in the breast epithelia. Different CK7 and CK20 IHC expression patterns are commonly used to distinguish many carcinoma types including breast carcinomas. Most breast cancers are CK7 positive and CK20 negative, making the combination of these cytokeratins an excellent biomarker combination. Approximately 80% of breast adenocarcinomas are CK7 positive and CK20 negative (Chu et al., 2000). 

IHC stain: cytoplasm 
Recommended CK20 IHC antibody: Recombinant Anti-Cytokeratin 20 antibody [EPR1622Y] - Cytoskeleton Marker (ab76126)
Recommended CK7 IHC antibody: Recombinant Anti-Cytokeratin 7 antibody [EPR1619Y] - Cytoskeleton Marker (ab68459)


APOBEC3B (apolipoprotein B mRNA editing catalytic polypeptide-like 3B)

APOBEC3B is expressed in ER-positive breast cancers and is used as a biomarker of poor prognosis for the disease and is a driver for downstream genetic mutations which accelerate the progression of breast cancer. These mutations make APOBEC3B positive breast cancers extremely drug-resistant (Zou et al., 2017). 

IHC stain: nuclear signal
Recommended IHC antibody: Anti-APOBEC3B antibody - N-terminal (ab191695)


Cell type-specific markers

FOXA1

The transcription factor FOXA1 has been shown to have a unique distribution within breast cancer cells compared to other cell types. FOXA1 binding is crucial for chromatin opening and the transcriptional activation of ER-α responsive genes within breast cancer cells (Cowper-Sallari et al., 2012). Studies have identified thousands of breast cancer-associated single nucleotide polymorphisms (SNPs) within the enhancer regions for FOXA1 (Meyer et al., 2012). 

IHC stain: nuclear signal
Recommended IHC antibody: Recombinant Anti-FOXA1 antibody [EPR10881] (ab170933)


GATA-binding protein 3 (GATA3)

GATA3 is a zinc finger transcription factor crucial for breast luminal epithelium differentiation. It is also a diagnostic biomarker for both primary and metastatic breast cancer and commonly found in luminal A and B breast cancer tissue. GATA3 also has a strong association with HER2 positive and ER- α positive hormone response in luminal breast cancers (Shaoxian et al., 2017). 

IHC stain: nuclear signal
Recommended IHC antibody: Recombinant Anti-GATA3 antibody [EPR16651] - ChIP Grade (ab199428)


CK5 (Cytokeratin 5)

CK5 is a cytokine found to be expressed in the basal cell layer of the mammary duct. Tumors that arise from these cells are also known to be CK5 positive and so CK5 is an excellent biomarker for the diagnosis of basal type breast cancers. The CK5 positive progenitor cells may also differentiate into glandular and myoepithelial cancer types (Laakso et al., 2005).  

IHC stain: cytoplasm and cell membrane
Recommended IHC antibody: Recombinant Anti-Cytokeratin 5 antibody [EP1601Y] - Cytoskeleton Marker (ab52635)


Smooth muscle myosin heavy chain (SMMHC)

SMMHC is expressed specifically in the contractile myoepithelial cells of the breast. A loss of the myoepithelial layer is commonly associated with invasive breast cancers. Markers such as SMMHC can be used in IHC to detect this layer more reliably than a hematoxylin and eosin stain alone (Zaha et al., 2014). 

IHC stain: cytoplasm
Recommended IHC antibody: Recombinant Anti-smooth muscle Myosin heavy chain 11 antibody [EPR5336(B)] (ab133567)


E-cadherin

E-cadherin is expressed at the cell junction of normal breast epithelial cells. A loss of E-cadherin is associated with a phenotypic switch by these cells to become invasive and migratory breast cancer cells. Loss of E-cadherin expression is commonly used as a biomarker for metastatic lobular breast carcinomas (Singhai et al., 2011).

IHC stain: Cell junctions
Recommended IHC antibody: Recombinant Anti-E Cadherin antibody [EP700Y] - Intercellular Junction Marker (ab40772)


Alpha smooth muscle actin (ACTA2)

Smooth muscle actin is highly expressed in normal breast myoepithelial cells. It is commonly used as a marker of this normal breast cell type. Smooth muscle actin is commonly used for histology in conjunction with SMMHC and calponins to mark out the myoepithelial layer. A combination of markers such as this is much more reliable than using hematoxylin and eosin stains alone (Zaha et al., 2014).

IHC stain: cytoplasm
Recommended IHC antibody: Anti-alpha smooth muscle Actin antibody (ab5694)


Calponin

Calponins are proteins found within the contractile components of the myoepithelium. Similarly to SMMHC and ACTA2, calponin stains are used as a marker of the myoepithelial layer in the diagnosis of invasive breast cancers (Zaha et al., 2014). 

IHC stain: cytoplasm
Recommended IHC antibody: Recombinant Anti-Calponin 1 antibody [EP798Y] (ab46794)Anti-Calponin 2 antibody (ab129331)Anti-Calponin 3 antibody (ab151427)


Delta-1-Catenin

Delta-1-Catenin is a member of the p120 family and acts as a binder of E-cadherin. Delta-1-Catenin can be used in histology to detect invasive lobular breast cancer, high tumor-node-metastasis stage, and lymph node metastasis. It is also strongly associated with HER2 positive breast cancers and can be used as an indicator of poor prognosis as it is thought to promote a malignant phenotype (Zhang et al., 2015). 

IHC stain: cytoplasm and cell membrane
Recommended IHC antibody: Recombinant Anti-delta 1 Catenin/CAS antibody [EPR357(2)] (ab92514)


CK14 (Cytokeratin 14)

CK14 is a cytokine found to be expressed in the basal cell layer of the mammary duct. It is most commonly found to be co-expressing with CK5 is this tissue type and similarly to CK5, the histological detection of CK14 is an excellent biomarker for the diagnosis of basal type breast cancers (Laakso et al., 2005).

IHC stain: cytoplasm
Recommended IHC antibody: Recombinant Anti-Cytokeratin 14 antibody [EPR17350] - Cytoskeleton Marker (ab181595)



Other markers

Ki67

Ki67 is an important protein involved in cell division and is commonly used as a marker of cellular proliferation. It is also used in breast cancer diagnosis to determine the level of cell proliferation which can be a prognostic marker and a good indication of well certain breast cancers will respond to endocrine therapy (Niazi et al., 2018). 

IHC stain: nuclear
Recommended IHC antibody: Anti-Ki67 antibody (ab15580)


Cyclin D1

Cyclin D1 is one of the main regulatory proteins of the cell cycle promoting the cell cycle progression from G1 to S phase. Mutations in cyclin D1 are amplified in many different types of cancer including many breast cancers. 50% of breast cancers will contain an overexpression of cyclin D1 (Mohammadizadeh et al., 2013). It has been used as a biomarker for poor prognosis for many breast cancer types, but some studies are beginning to suggest that it could also suggest a positive outcome if expressed in some luminal subtypes of breast cancer (Ortiz et al., 2017). 

IHC stain: nuclear
Recommended IHC antibody: IHC antibody: Recombinant Anti-Cyclin D1 antibody [EPR2241] - C-terminal (ab134175)


Cyclooxygenase-2 (COX-2)

COX-2 is an enzyme responsible for producing prostanoids. Its expression in breast tissue correlates strongly with breast cancer development. Overexpression of COX-2 has been shown to drive breast cancer phenotypes and blocking the action of this protein also shows potential for breast cancer therapy. There is also a strong link between COX-2 overexpression in breast adipose tissue and cancer progression linked to obesity (Harris et al., 2014). 

IHC stain: cytoplasm
Recommended IHC antibody: Recombinant Anti-COX2 / Cyclooxygenase 2 antibody [EPR12012] (ab179800)


Caveolin-1

Caveolin-1 is the main component of caveolae, small invaginations found in the cell membrane. It’s also known to play a key role in cell proliferation, invasion, and breast cancer metastasis. It is also used as a biomarker for breast cancer treatments and disease outcome. High expression of caveolin-1 is a sign of poor prognosis an indicates are more aggressive metastatic breast cancer (Qian et al., 2019). 

IHC stain: cell membrane
Recommended IHC antibody: Recombinant Anti-Caveolin-1 antibody [E249] - Caveolae Marker (ab32577)


Peroxisome proliferator-activated receptor (PPAR-γ)

PPAR-γ is a well-studied nuclear hormone receptor. PPAR-γ has been implicated in different types of breast cancer in which its ligands inhibit proliferation and angiogenesis and induce apoptosis (Fenner et al., 2005). It has also been shown to play a role in promoting breast tumor growth through the maintenance of HER2 positive endothelial breast cancer stem cells making its expression a good biomarker for this cell type (Wang et al., 2013).

IHC stain: nuclear
Recommended IHC antibody: Anti-PPAR gamma antibody - ChIP Grade (ab45036)

​​Lung cancer biomarkers

Lung cancer is one of the leading causes of cancer-related death worldwide, accounting for approximately one-third of cancer-related deaths (Siegel et al., 2012). The diagnosis of different lung cancers relies heavily on the use of IHC-based diagnostic tests and continued research into lung cancer biomarkers that can be used in IHC. There is an increasing number of antibodies available for detecting lung cancer-specific biomarkers used to determine different types of lung cancer and their cells of origin. These different cancer types include; adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.

Here we look at some of the most common primary IHC markers for lung cancer, metastatic markers, and markers for proliferation and disease progression. We also give our recommended antibody for use in IHC.

Primary IHC markers
Aryl hydrocarbon receptor (AHR) 

AHR is a transcription factor highly expressed in bronchial epithelial cells where it affects cell proliferation, differentiation, and cell-cell adhesion. It plays a key role in diseases such as bronchitis and asthma, but it is also strongly implicated in the progression of lung cancer. It does this through the promotion of cell proliferation, angiogenesis, inflammation, and apoptosis (Tsay et al., 2013). AHR expression is also linked with smoking-related tumors as it may upregulate CYP1A1 releasing harmful factors into the lung tissue. It is, therefore, a marker of poor prognosis for lung cancer patients (Tsay et al., 2013).  

IHC stain: nuclear and cytoplasm
Recommended IHC antibody: Anti-Aryl hydrocarbon Receptor antibody (ab84833)


Programmed death-1 ligand (PD-L1)

PD-L1 is a transmembrane protein which acts by inhibiting T cell activation and proliferation. PD-L1 protein detection by IHC testing is widely used as a predictive biomarker assay for anti–PD-1/PD-L1 therapies for several cancer types including lung cancer. Non-small cell lung cancer (NSCLC) accounts for 75% of all lung cancers and approximately 50% of NSCLC cases will have expression of PD-L1 in histology carried out on patient biopsies making it a strong biomarker for this cancer type.

Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-PD-L1 antibody [73-10] (ab228415)
Immunohistochemical analysis of paraffin-embedded Human breast carcinoma tissue labeling ErbB 2 with ab16662, followed by a ready-to-use Goat Anti-Rabbit & Mouse IgG (HRP).

IHC stain: cell membrane
Recommended IHC antibody: Recombinant Anti-PD-L1 antibody [73-10] (ab228415)


PD1 (PDCD1/CD279)

Programmed death-1 receptor is the receptor to transmembrane ligand PD-L1 (above) and is found to be expressed on the surface of T-cells. Tumors use this PD-1/PD-L1 interaction to evade and suppress the immune response. These interactions are commonly seen in NSCLC as described above for PD-L1. Nivolumab; an anti-PD-1 drug is approved for use in squamous NSCLC (Chen et al., 2012).

IHC stain: cell membrane
Recommended IHC antibody: Recombinant Anti-PD1 antibody [CAL20] (ab237728)​​​


Surfactant protein A (SPA) 

SPA is a large protein expressed within alveoli cells of the lung and is responsible for fighting infectious disease and reducing alveoli surface tension. SPA is also a biomarker used to detect adenocarcinoma in the lung. It is thought to be a marker of good prognosis as SPA is known to reduce tumor progression in the lung by recruiting natural killer cells to the site of the tumor (Mitsuhashi et al., 2013).

IHC stain: secreted protein within the extracellular space
Recommended IHC antibody: Anti-Surfactant Protein A/PSAP antibody [6F10] (ab51891)


SOX2

SOX2 is a transcription factor that plays a crucial role in the developing embryonic lung. It is also important for the formation of the proximal airways where it is used as a marker of proliferation and lung stem cells. It is also found to be overexpressed in over 80% of patients with lung squamous cell carcinoma (LSCC), a type of NSCLC. It is therefore commonly used as a marker of lung cancer cells derived from this squamous cell lineage (Mollaoglu et al., 2019).

IHC stain: nuclear
Recommended IHC antibody: Recombinant Anti-SOX2 antibody [SP76] (ab93689)


MET

The MET proto-oncogene is a transmembrane tyrosine kinase receptor and its signaling cascade is involved in proliferation, apoptosis, and cellular migration. It also plays a role in the progression of NSCLC. Overexpression of MET in NSCLC leads to a misregulation of proliferation and cell migration leading to a more aggressive cancer (Salgia et al., 2017).

IHC stain: cell membrane
Recommended IHC antibody: Recombinant Anti-Met (c-Met) antibody [EP1454Y] - N-terminal (ab51067)


Fas

Fas (or apoptosis antigen 1 APO-1) is a death receptor expressed on the cell surface which mediates apoptosis. Misregulation of apoptosis in normal cell types can lead to the progression of cancer. (FasL the FAS ligand) overexpression has been shown as a prognosis of advanced cancer stage in NSCLC (Viard-Leveugle et al., 2003).

IHC stain: secreted protein and cell membrane
Recommended IHC antibody: Recombinant Anti-Fas antibody [EPR5700] (ab133619)

Metastatic markers
C-reactive protein (CRP)

Increased levels of CRP are an indication of inflammation. It is commonly seen to be expressed in lung cancer patients who smoke. Smoking leads to chronic lung inflammation and the upregulation of several inflammation response genes including CRP. Expression of CRP is a marker of lung squamous cell carcinomas and small-cell cancers but not adenocarcinoma of the lung (Chaturvedi et al., 2010).

IHC stain: secreted protein
Recommended IHC antibody: Recombinant Anti-C Reactive Protein antibody [Y284]


MCM6

MCM6 is a chromosomal maintenance protein important for the cell cycle and mitosis and has been associated with increasing the metastatic potential of various cancer types including lung cancers. It has been shown to be expressed in around 50% of NSCLC patient samples and high expression levels of MCM6 is linked to a poor prognosis of this disease. Its expression is also seen to be higher in patients who smoke (Liu et al., 2017).

IHC stain: nuclear
Recommended IHC antibody: Anti-MCM6 antibody [EPR17686] (ab201683)


KIAA1522

KIAA1522 is a relatively unknown protein but it has been recently implicated as a potential novel biomarker for NSCLC. This uncharacterized gene has been pulled out of a few large-scale screening studies looking to identify new biomarkers for NSCLC. Further experiments showed that KIAA1522 is highly expressed in the NSCLC tissues and indicates poor survival of NSCLC patients (Liu et al., 2016).

IHC stain: cytoplasm
Recommended IHC antibody: Anti-KIAA1522 antibody (ab122203)

Other markers
Glutathione S-transferase pi 1 (GSTP1)

GSTP1 is an enzyme responsible for breaking down toxic compounds. In the lung, GSTP1 is highly expressed and is known to carry out the metabolism of carcinogens carried into the lung through smoking. Certain variants of GSTP1 are used as markers of lung cancer prognosis. The Ile105Val variant is associated with a reduced risk of lung cancer and a reduction in mortality from the disease (Nørskov et al., 2017).

IHC stain: cytoplasm
Recommended IHC antibody: Recombinant Anti-GST3 / GST pi antibody [EPR8263] (ab138491)


Ki67

Ki67 is an essential protein involved in cell division and is commonly used as a marker of cellular proliferation. IHC staining for Ki-67 is a commonly used method for evaluating proliferative activity in various tumor types including lung tumors. Studies suggest a key role of Ki-67 as a prognostic marker of NSCLC (Kriegsmann et al., 2016).

IHC stain: nuclear
Recommended IHC antibody: Anti-Ki67 antibody (ab15580)


MCM7

MCM7 is a chromosomal maintenance protein important during the cell cycle and has been associated with various cancer types including lung cancers. Both MCM7 and ki67 (the proliferation marker) are highly expressed in squamous cell carcinomas of the lung. Both are associated with poor prognosis in the disease. MCM7 can also be used as an IHC biomarker from bronchial brushings (Liu et al., 2012).

IHC stain: nuclear
Recommended IHC antibody: Recombinant Anti-MCM7/PRL antibody [EP1974Y] (ab52489)


Achaete-scute complex 1 (ASCL1)

ASCL1 is a transcription factor necessary for neuroendocrine lung development and the growth of both SCLC and NSCLC. It acts as a marker of poor prognosis in NSCLC and looks promising as a potential druggable target for the treatment of NSCLC (Augustyn et al., 2014).

IHC stain: Mitochondrion outer membrane. Peroxisome membrane. Microsome membrane. Endoplasmic reticulum membrane.
Recommended IHC antibody: Recombinant Anti-ACSL1 antibody [EPR13499] (ab177958)

​​Colorectal cancer biomarkers

Colorectal cancer (CRC), is one of the most commonly diagnosed cancers amongst men and women with an overall 5-year survival of below 60%. (Siegel et al 2017; Trinh et al 2016). IHC has become an important application for the identification and classification of carcinomas of unknown primary site (CUPs, Selves 2018) and shows great promise in the identification of different CRCs.

Here we look at some of the most common primary IHC markers for CRC, cell-type specific markers, and markers for angiogenesis and disease progression. We also give our recommended antibody for use in IHC.

Primary IHC markers
Calretinin

Calretinin is a calcium-binding protein which plays a role in message targeting and intracellular calcium buffering. While absent in normal colonocytes, it is expressed in most poorly differentiated colon carcinomas (Vonlanthen et al 2007). Strongly positive calretinin staining in colon medullary carcinoma, as well as correlations between the expression of calretinin and degree of differentiation in human colorectal adenocarcinomas, have been reported emphasizing the potential of calretinin as an IHC biomarker for bowel cancer (Gotzos et al 1999; Winn et al 2008). 

IHC stain: cytoplasmic and nuclear
Recommended antibody: Recombinant Anti-Calretinin antibody [EP1798] (ab92341)


MUC2

MUC2 is part of the mucin family and characteristically observed in goblet cells of small and large bowel mucosa (Betge et al 2016). It is involved with coating the epithelia of the intestines, airways, and other mucus membrane-containing organs. Loss of MUC2 expression has been reported to be a predictor of adverse outcome and further prospective studies that evaluate adjuvant chemotherapy in stages II and III colon cancer should include MUC2 expression analysis for patient stratification (Betge et al 2016).

Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-MUC2 antibody [EPR6144] (ab133555)
Immunohistochemical analysis of paraffin embedded human colon tissue labeling MUC2 with ab133555 at a dilution of 1/100.

IHC stain:  Intestine, secreted into the inner and outer mucus layers
Recommended antibody: Recombinant Anti-MUC2 antibody [EPR6144] (ab133555)


COX-2

COX-2 is an inducible enzyme that regulates prostaglandin synthesis and is overexpressed in several epithelial cancers. It is involved in the regulation of apoptosis, angiogenesis, and tumor cell invasiveness which contribute to its effects on tumorigenesis. Multiple studies have shown that selective COX-2 inhibitors are a great targeted approach to the chemoprevention of CRC (Sinicrope et al 2004; Herendeen et al, 2003).

IHC stain: microsome membrane and endoplasmic reticulum membrane
Recommended antibody: Recombinant Anti-COX2 / Cyclooxygenase 2 antibody [EPR12012] (ab179800)


Cadherin-17 (CDH17)

CDH17, also known as LI Cadherin, is one of a group of cadherins that act as calcium-dependent cell adhesion proteins that preferentially interact with themselves in a homophilic manner in connecting cells (uniprot.org).  High CDH17 expression has been associated with liver metastasis, a major cause of death associated to colorectal cancer, and poor survival of patients (Bartolomé et al, 2013).

Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-LI Cadherin antibody [EPR3996] (ab109190)
Recombinant anti-LI Cadherin antibody (ab109190) showing positive staining in normal colon tissue.

IHC stain: cell membrane
Recommended antibody: Recombinant Anti-LI Cadherin antibody [EPR3996] (ab109190)


GPA33

The GPA33 gene codes for A33 antigen, a transmembrane glycoprotein that is expressed in normal colonic and small bowel epithelium as well as more than 95% of human colon cancers (Heath et al, 1997). IHC in CRC tissue has shown strong A33 membrane staining in samples of well-differentiated tumors (Baptistella et al, 2016), and there are also proposals for using antibodies to GPA33 as a potentially potent radioimmunotherapy regimen for GPA-33 positive CRC tumors in humans (Cheal et al, 2017).

IHC stain: cell membrane
Recommended antibody: Recombinant Anti-GPA33 antibody [EPR4240] (ab108938)


EGFR

Epidermal growth factor receptor (EGFR) is usually involved in cell growth and is recognized as an important player in CRC initiation and progression (Markman et al, 2010). In late-stage colorectal cancer, the most commonly used targeted therapies are monoclonal antibodies that prevent EGFR activation (Bertotti et al, 2015). However, future development of anti-EGFR directed nanoparticles that could inhibit overactive EGFR signals could potentially reduce CRC risk (Pabla et al, 2015).

IHC stain: secreted and cell membrane
Recommended antibody: Recombinant Anti-EGFR antibody [E235] (ab32077)


Cell type specific markers
CDX2

CDX2 is a transcription factor expressed specifically in the intestine where it is involved in the maintenance of intestinal cell types. Low CDX2 expression in CRC is associated with advanced stages of cancer progression, vessel invasion, and metastasis. Over 20% of CRC show some reduction of CDX2 protein by histology. Seeing normal or high levels of CDX2 expression is a biomarker for a good prognosis for survival from the disease (Graule et al., 2018).

IHC stain: nuclear
Recommended IHC antibody: Recombinant Anti-CDX2 antibody [EPR2764Y] (ab76541)


MOC-31/Ep-CAM 

MOC-31 is a commonly used biomarker used in colorectal adenocarcinoma to discriminate cancer cells from mesothelial cells. Being able to distinguish between adenocarcinoma and mesothelial cells by histology is crucial for clinicians to be able to correctly diagnose and assign treatment to patients. Treatment assignment can be difficult when the cancer is a mix of both adenocarcinoma and mesothelial cells (Kundu et al., 2011). 

IHC stain: cell membrane
Recommended IHC antibody: Recombinant Anti-EpCAM antibody [EPR20532-225] (ab223582)


Villin

Villin is an actin-binding protein expressed in the epithelial cells lining the gut and has been shown to regulate epithelial-mesenchymal transition (EMT) in colorectal cancers. Microsatellite instability (MSI) colorectal cancers have also been shown to have very low levels of Villin expression compared to normal gut epithelial cells. This loss of Villin leads to poorly differentiated histology of the CRC (Arango et al., 2012)

IHC stain: cytoplasm
Recommended IHC antibody: Recombinant Anti-Villin antibody [EPR3491(3)] (ab133510)


CK20 (Cytokeratin 20) and CK7 (Cytokeratin 7)

CK7 and CK20 are cytokeratins expressed in the gut epithelia. Different CK7 and CK20 IHC expression patterns are commonly used to distinguish colorectal adenocarcinomas. Most colorectal cancers are CK7 negative and CK20 positive, making the combination of these cytokeratins an excellent biomarker combination. CK7 and CK20 expression varies between colorectal carcinomas according to histological grade and tumor location. CK7 expression is seen in tumors with lymph node non-metastatic tumors (Bayrak et al., 2011).

IHC stain: cytoplasm
Recommended CK20 IHC antibody: Recombinant Anti-Cytokeratin 20 antibody [EPR1622Y] - Cytoskeleton Marker (ab76126)
Recommended CK7 IHC antibody: Recombinant Anti-Cytokeratin 7 antibody [EPR1619Y] - Cytoskeleton Marker (ab68459)


Angiogenesis markers
VEGF

VEGF is a heparin-binding glycoprotein with potent angiogenic activity within endothelial cells. Angiogenesis is crucial for the progression of colorectal carcinoma. VEGF is expressed in around 50% of colorectal cancers and shows very low expression in normal colonic mucosa making it a good biomarker for the diagnosis of CRC from histology samples (Bendardaf et al., 2008).

IHC stain: secreted protein
Recommended IHC antibody: Recombinant Anti-VEGFA antibody [EP1176Y] - C-terminal (ab52917)


Other markers
p53

The tumor suppressor p53 is a transcription factor involved in cell cycle arrest and apoptosis under cellular stress. Mutations within p53 is one of the most frequent triggers leading to the progression of CRC and is found in 34% of the proximal colon tumors, and 45% of distal colorectal tumors. Patients with mutant p53 have a poorer prognosis than those with wild-type p53 (Li et al., 2015).

IHC stain: cytoplasm and strong nuclear
Recommended IHC antibody: Anti-p53 antibody [DO-1] - ChIP Grade (ab1101)


Ki67

Ki67 is an important protein involved in cell division and is commonly used as a marker of cellular proliferation. Quantifying Ki67 expression by IHC will give you the Ki67 labeling index which is commonly used in clinical pathology to estimate cancer prognosis. High Ki67 expression is thought to be an indication of a good prognosis for patients with colorectal cancer. Ki67 IHC stains are therefore a good biomarker for CRC (Melling et al., 2016).

IHC stain: nuclear
Recommended IHC antibody: Anti-Ki67 antibody (ab15580)


Insulin-like growth factor binding protein 2 (IGFBP2)

IGFBP-2 interacts with the extracellular matrix, proteoglycans and integrin receptors within many different cell types. It may also act as a transcription factor to stimulate gene expression. Studies have shown that IGFBP-2 is uniquely distributed at the bottom of human colonic crypts and that increased levels of IGFBP-2 can be seen in many colorectal cancers.  This expression co-localizes with the phosphorylated p65 subunit of NF-kB making these good biomarkers for CRC (Ben-Shmuel et al., 2013).

IHC stain: Secreted protein
Recommended IHC antibody: Recombinant Anti-IGFBP2 antibody [EPR18012-257] (ab188200)


PKM2

The M2 isoform of PK (PKM2) is a glycolytic enzyme involved in aerobic glycolysis and anabolic metabolism in cancer cells. PKM2 also promotes the transcription of Oct-46, HIF-1α7, STAT38, and β-catenin during the progression of various cancers. PKM2 is expressed in normal colon tissues but is often overexpressed in colorectal cancers including colitis-induced colorectal cancers (Kim et al., 2019).

IHC stain: nuclear and cytoplasm
Recommended IHC antibody: Recombinant Anti-PKM antibody [EPR10138(B)] (ab150377)


References

Header image
Detecting cancer in human tissues, LM. Credit: Aamir Ahmed, Jane Pendjiky and Michael MillarCC BY

Breast cancer biomarker references

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Colorectal cancer biomarker references

Baptistella, A. R., Salles Dias, M.V., Aguiar, S Jr., Begnami, M.D., Martins, V.R. (2016). Heterogeneous expression of A33 in colorectal cancer: possible explanation for A33 antibody treatment failure Anticancer Drugs. 27(8):734-7

Bartolomé, R. A., Barderas, R., Torres, S., Fernandez-Aceñero, M. J., Mendes, M., García-Foncillas, J., Lopez-Lucendo, M. & Casal, J. I.  (2013). Cadherin-17 interacts with α2β1 integrin to regulate cell proliferation and adhesion in colorectal cancer cells causing liver metastasis Oncogene volume 33, pages 1658–1669

Bertotti, A., Papp, E., […]Velculescu, V. E., (2015). The genomic landscape of response to EGFR blockade in colorectal cancer Nature volume526, pages 263–267

Betge, J., Schneider, N. I., Harbaum, L., Pollheimer, M. J., Lindtner, R. A., Kornprat, P., Ebert, M. P., and Langner, C. (2016). MUC1, MUC2, MUC5AC, and MUC6 in colorectal cancer: expression profiles and clinical significance Virchows Arch.; 469(3): 255–265.

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Herendeen J. M., Lindley C., (2003). Use of NSAIDs for the chemoprevention of colorectal cancer Ann Pharmacother; 37(11):1664-74.

Markman B., Javier Ramos F., Capdevila J., Tabernero J. (2010). EGFR and KRAS in colorectal cancer. Adv Clin Chem; 51:71-119.

Pabla, B., Bissonnette, M., and Konda, V. J., (2015). Colon cancer and the epidermal growth factor receptor: Current treatment paradigms, the importance of diet, and the role of chemoprevention World J Clin Oncol. Oct 10; 6(5): 133–141.

Selves, J., Long-Mira, E., Mathieu, M., Rochaix, P., and Ilié, M. (2018). Immunohistochemistry for Diagnosis of Metastatic Carcinomas of Unknown Primary Site Cancers (Basel); 10(4): 108.

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Trinh A., Trumpi K., De Sousa E., Melo F., Wang X., de Jong J. H., Fessler E., Kuppen P. J., Reimers M. S., Swets M., Koopman M., Nagtegaal I. D., Jansen M., Hooijer G. K., Offerhaus G. J., Kranenburg O., Punt C. J., Medema J. P., Markowetz F., Vermeulen L. (2017).

Vonlanthen, S., Kawecki, T. J., Betticher, D. C., Pfefferli, M., and Schwaller, B. (2007).  Heterozygosity of SNP513 in Intron 9 of the Human Calretinin Gene (CALB2) is a Risk Factor for Colon Cancer ANTICANCER RESEARCH 27: 4279-4288

Winn B., Tavares, R., Fanion, J., Noble, L., Gao, J., Sabo, E., and Resnick, M. B. (2008).  Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation Hum Pathol; 40(3): 398–404.

 



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