Ovarian cancer biomarkers

Find the right cancer biomarker for your research using our cancer immunohistochemistry (IHC) guide to ovarian cancer.

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Ovarian cancer is the leading cause of gynecologic cancer death in women and impacts female life and health worldwide. The high death rate in this disease is due to the late stage of disease diagnosis. Although radical surgical tumor debulking and platinum plus paclitaxel-based chemotherapy are currently established therapies for the treatment of ovarian cancer, the 5-year survival rate is still around 40%. The ability to sensitively and specifically predict the presence of early ovarian cancer, disease status, stage, and associated therapeutic efficacy, has the potential to revolutionize ovarian cancer detection and treatment.

Consequently, the identification and validation of applicable diagnostic and prognostic ovarian cancer biomarkers are essential to improve patient outcomes.

CD9

CD9 is widely expressed in Tubo-ovarian high-grade serous carcinoma (HGSC) and represents an important new therapeutic target with immediate relevance for NK immunotherapy.

CD9 suppresses anti-tumor cytokine production and cytotoxicity in NK-92 cells.

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References

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Paired box 8 (PAX8)

PAX8 is a transcription factor essential in organogenesis, morphogenesis, cell growth, and differentiation. PAX8 binds a large number of genomic sites and forms transcriptional hubs. At a subset of these, PAX8, together with PRDM3, regulates a specific gene expression module involved in adhesion and extracellular matrix. PAX8 is highly expressed in benign and malignant primary epithelial ovarian carcinomas but not in metastatic ovarian cancer.

PRDM3 is amplified in ovarian cancers. The MECOM locus and PAX8 sustain i n vivo tumor growth, further supporting that the identified function of the MECOM locus underlies PAX8-driven oncogenic functions in ovarian cancer. High expression levels of PAX8 correlate with shorter survival rates, and PAX8 acts as a diagnostic and prognostic biomarker for ovarian cancer.

IHC analysis of paraffin-embedded human ovarian cancer tissue labeling PAX8 with ab239363 at 1/2000 dilution followed by a ready to use Rabbit specific IHC polymer detection kit HRP/DAB (ab209101). Nuclear staining in human ovarian cancer (PMID: 21317881).

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References

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MUC16

Alternative names CA125

This membrane-associated mucin, found in the cornea and conjunctiva, in the respiratory tract, and female reproductive tract epithelium, forms a lubricating barrier against foreign particles and infectious agents. This biomarker is 79% sensitive for ovarian cancer and is considered the most reliable diagnostic marker for ovarian cancer and a potential cancer therapeutic target. Assayed as a serum biomarker for ovarian cancer diagnosis, MUC16 is also used in IHC to distinguish ovarian origins of metastases.

FFPE IHC of human ovarian serous papillary carcinoma tissue sections labeling MUC16 with purified ab110640 at 1:1000 dilution (0.12 μg/mL). Negative control: PBS instead of the primary antibody.

Anti-MUC16 antibody [EPR1020(2)] (ab110640)

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References

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Wilms tumor protein (WT1)

This ovarian cancer biomarker is used in IHC to differentiate ovarian carcinoma (WT1+) from breast or pancreatic carcinomas (WT1-). It is a robust diagnostic and prognostic biomarker of ovarian cancers and is used in combination with PAX8 to refine diagnosis in phenotype-overlapping cases of serous cancers.

FFPE IHC of human ovarian serous adenocarcinoma tissue sections labeling Wilms tumor protein with Anti-WT1 (ab89901) at 1:500 dilution (0.49 μg/mL). Negative control: PBS instead of the primary antibody.

Anti-Wilms Tumor Protein antibody [CAN-R9(IHC)-56-2] (ab89901)

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References

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p53

This tumor suppressor protein is commonly mutated in many cancer types and overexpressed in over 96% of high-grade serous ovarian cancer. p53 mutations and p53 overexpression are both related to shorter patient survival, with the strongest predictor of the outcome being a combination of both mutations and overexpression. As an IHC biomarker, p53 expression is used to differentiate malignant cancers (p53+) from reactive and metaplastic conditions (p53-).

Formalin-fixed, paraffin-embedded human ovarian adenocarcinoma tissue stained for p53 using ab227655 at 1/100 dilution in IHC analysis.

Anti-p53 antibody [SP161] (ab227655)

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References

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Human epididymis protein 4 (HE4)

HE4 is a protease inhibitor that is approved by the United States FDA for monitoring recurrence or progressive disease in patients with epithelial ovarian cancer. This biomarker is used in combination with MUC16 for the diagnosis of ovarian cancer, with some reports suggesting that HE4 offers increased specificity over MUC16 for the diagnosis of early ovarian cancer.

FFPE IHC of human ovarian carcinoma labeling HE4 with ab200828 at 1/1000 dilution. Negative control: PBS instead of the primary antibody.

Anti-HE4 antibody [EPR16658] (ab200828)

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References

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CDKN2A/p16INK4a

cDKN2a is a tumor suppressor protein, which, when silenced in ovarian cancer, can promote carcinogenesis. Increased expression of CDKN2A, the gene product of p16INK4a, in ovarian cancer has been associated with progression and unfavorable outcomes, though this may be histotype dependent, with some studies suggesting no overall association with survival in high-grade serous tumors, block expression of this biomarker associated with shorter overall survival in endometriosis-associated carcinomas, clear cell, and endometrioid cancers, and absence of CDKN2A expression associated with shorter overall survival in low-grade serous ovarian carcinoma.

Anti-CDKN2A/p16INK4a antibody [EPR1473] - C-terminal (ab108349)

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References

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Estrogen receptor alpha

Estrogen receptor alpha is an established biomarker in the prognosis and treatment prediction of breast cancer. However, it is also emerging as a valuable biomarker in ovarian cancer. ERα staining in ovarian cancer IHC correlates with a positive response to anti-estrogen treatment (e.g., tamoxifen) or chemotherapy and better clinical outcomes.

ERβ staining shows variable results dependent upon the stage and grade of ovarian cancer, with some studies showing negative expression, correlates with favorable outcomes. ER expression in ovarian carcinoma is associated with better differentiated, more advanced tumors. ER levels are typically higher in high-grade, low-grade serous, and endometrioid carcinoma but lower in mucinous and clear-cell carcinoma.

FFPE IHC of human ovarian adenocarcinoma tissue stained for estrogen receptor alpha using ab16660 at 1/200 dilution.

Anti-Estrogen Receptor alpha antibody [SP1] (ab16660)

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References

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Progesterone receptor

This biomarker is often used in conjunction with an estrogen receptor in IHC assays of ovarian carcinoma. The positivity of PR-B expression is correlated with a positive response to chemotherapy and positive patient outcomes, though it offers limited additional information over ER alone.

Anti-Progesterone Receptor antibody [SP2] (ab16661)

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Human epidermal growth factor receptor 2 (HER2)

Alternative names c-erbB2, neu, ERBB2, CD340

HER2 is a tyrosine kinase that dimerizes with members of the EGFR family for activity. Under normal conditions, HER2 acts to influence cellular migration, differentiation, and interactions between cells.

HER2 mutants offer a well-established breast cancer biomarker, but its use as an ovarian cancer biomarker is more controversial15. In ovarian cancer, HER2 expression is more commonly seen in the serous subtype, in older patients, and in patients with advanced-stage and high-grade differentiation cancers, leading to poor patient prognosis for ovarian cancer patients3.

Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) analysis of Human breast carcinoma tissue sections labeling EErbB2 / HER2 with purified ab134182 at 1:1600 dilution (0.68 µg/mL).

Anti-ErbB2 / HER2 antibody [EP1045Y] (ab134182)

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References

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Osteopontin

Osteopontin is a secreted, integrin-binding matrix phosphorylated glycoprotein that is overexpressed in many advanced cancers. It plays a role in many physiological and pathological processes; wound healing, inflammation, immune response, and tumorigenesis. Osteopontin promotes ovarian cancer progression and cell survival and increases HIF-1alpha expression through the PI3-K/Akt pathway. Osteopontin may serve as a potential diagnostic biomarker for ovarian cancer, and could potentially influence cancer therapy and be used in the development of novel anti-tumor treatments.

Anti-Osteopontin antibody [EPR21139-316] (ab214050)

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References

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Programmed cell death protein 1 (PD1)

Alternative names CD279

This well-known immune checkpoint receptor controls lymphocyte activation by providing negative signals in conjunction with signals from lymphocyte antigen receptors. PD1 expression in ovarian cancers is associated with advanced stages of the disease in patients with high-grade tumors.

PD1 expression in IHC is an emerging biomarker for ovarian cancer diagnosis and poor patient prognosis. This biomarker is used to stratify patients for immuno-therapy with PD1 inhibitors, such as nivolumab, with the therapeutic effect seen only in a subset of patients and additional biomarkers required to accurately determine therapeutic efficacy.

Recombinant Anti-PD1 antibody [CAL20] (ab237728)

PD1 antibodies

References

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IGFBP2

Insulin-like growth factor binding protein 2 (IGFBP2) is overexpressed in malignant ovarian tissues and in the serum and cystic fluid of ovarian cancer patients. IGFBP2 overexpression does not correlate with the stage of ovarian cancer. This biomarker has shown some utility in the differentiation of serous carcinoma from clear cell carcinoma for ovarian cancer diagnosis. IGFBP2 enhances the invasion capacity of ovarian cancer cells; consequently, blockage of IGFBP2 may thus constitute a viable strategy for targeted cancer therapy.

Recombinant Anti-IGFBP2 antibody [EPR18012-257] (ab188200)

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References

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Kallikrein 8

This steroid-hormone-regulated serine protease is not typically expressed in normal ovarian tissue, but elevated levels have been shown in ovarian cancers, suggesting this biomarker offers potential use in the diagnosis of ovarian cancer.

Kallikrein 8-positive tumors have been associated with lower-grade tumors, no residual tumor after surgery, and optimal debulking success, suggesting Kallikrein 8 may act as a favorable prognostic biomarker for ovarian cancer.

Anti-Kallikrein 8/KLK8 antibody [EPR5752(2)] (ab150395)

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References

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Cytokeratin 7 CK7

CK 7 is an established biomarker to differentiate primary ovarian carcinoma from metastatic colorectal carcinoma of the ovary. This biomarker can also be used in IHC analysis of ovarian cancer to differentiate primary serous tumors (negative) from primary mucinous tumors (positive). CK7 is negatively expressed in yolk sac tumors but diffusely expressed in both clear cell carcinoma and endometrioid adenocarcinoma, making it a useful biomarker (often used in conjunction with EMA) to differentiate ovarian cancer subtypes.

FFPE IHC of human ovarian carcinoma tissue stained for Cytokeratin 7 using ab68459.

Anti-Cytokeratin 7 antibody [EPR1619Y] - Cytoskeleton Marker (ab68459)

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References

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Cytokeratin 20 (CK20)

CK20 is used as a biomarker in conjunction with CK7 to diagnose primary mucinous tumors of the ovary. The absence of this biomarker in CK7+ ovarian tumors is indicative of ovarian adenocarcinoma, including endometrioid, clear cell, serous and seromucous carcinomas. CK20 is also used in pathological analysis to discriminate between ovarian tumors and secondary metastatic tumors of the ovary.

Anti-Cytokeratin 20 antibody [EPR1622Y] - Cytoskeleton Marker (ab76126)

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References

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Pan-cytokeratin

This cytokeratin cocktail recognizes K1 - 8, 10, 14 - 16 and 19, but does not detect CK17 or CK18. It is commonly used in the IHC of ovarian tissue in conjunction with vimentin.

Pan-cytokeratin staining shows membranous staining in the majority of tumor types and epithelial labeling in normal tissue. Pan-cytokeratin typically shows strong staining across healthy and tumorous tissue.

Anti-pan Cytokeratin antibody [C-11] (ab7753)

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References

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Vimentin

Vimentin is a type III intermediate filament protein that anchors the structure of the cytoplasm. In the IHC of normal ovarian tissue, vimentin localizes to surface epithelium and granulosa cells. The variable staining of this biomarker in different ovarian carcinomas, from no staining in benign mucinous tumors or serous cystadenomas to strong cytoplasmic staining in malignant serous tumors, can be used to differentially diagnose various ovarian cancer types.

IHC vimentin staining using recombinant anti-vimentin antibody [EPR3776] - cytoskeleton marker (ab92547)

IHC vimentin staining using recombinant anti-vimentin antibody [EPR3776] - cytoskeleton marker (ab92547).

We recommend Recombinant Anti-Vimentin antibody [EPR3776] (ab92547)

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References

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Forkhead box L2 (FOXL2)

FOXL2 belongs to a large family of forkhead FOX transcription factors. It is one of the first genes expressed in female gonad development, required for proper granulosa cell differentiation during folliculogenesis, and maintains a strong expression in granulosa cells throughout life. FOXL2 mutations are present in 70 - 95% of ovarian adult granulosa cell tumors but not in ovarian fibromas or ovarian juvenile granulosa cell tumors.

Consequently, IHC analysis of FOXL2 mutation is used by pathologists to distinguish diffuse adult granulosa cell tumors from cellular fibroma in ovarian tissue.

IHC staining of human ovary tissue with recombinant anti-FOXL2 antibody [EPR23523-68] (ab246511)

IHC staining of human ovary tissue with recombinant anti-FOXL2 antibody [EPR23523-68] (ab246511).

Anti-FOXL2 antibody [EPR23523-68] (ab246511)

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References

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ARID1A

This biomarker is a member of the SWI/SNF ATP-dependent chromatin-remodeling complexes. It functions in cellular differentiation and development. Expressed in the nucleus of normal tissue, inactivation of this protein and loss of expression is seen in ~50% of ovarian clear cell carcinoma and may be an early event in the development of endometriosis-associated ovarian carcinomas.

Anti-ARID1A antibody [EPR13501-73] (ab182561)

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References

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References

CD9

Gonzalez, V. D.,, Huang, Y. W.,, et al. High-grade serous ovarian tumor cells modulate NK cell function to create an immune-tolerant microenvironment. Cell reports 36 (9), (2021)

Paired box 8 (PAX8)

Chai, H. J., Ren, Q., Fan, Q., et al. PAX8 is a potential marker for the diagnosis of primary epithelial ovarian cancer. Oncol Lett. 5 (14),5871-5875 (2017)

Lilac, L., Carcangiu, M. L., Canevari, S., et al. The value of PAX8 and WT1 molecules in ovarian cancer diagnosis. Rom J Morphol Embryol 1 (54),17-27 (2013)

MUC16

Felder, M., Kapur, A., Gonzalez-Bosquet, J., et al. MUC16 (CA125): tumor biomarker to cancer therapy, a work in progress. Mol Cancer (13),129 (2014)

Wilms tumor protein (WT1)

Lilac, L., Carcangiu, M. L., Canevari, S., et al. The value of PAX8 and WT1 molecules in ovarian cancer diagnosis. Rom J Morphol Embryol 1 (54),17-27 (2013)

Taube, E. T., et al. Wilms tumor protein 1 (WT1)-- not only a diagnostic but also a prognostic marker in high-grade serous ovarian carcinoma. Gynecologic Oncology 140 (3), (2016)

p53

Cole, A. J., Dwight, T., Gill, A. J., et al. Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing. Sci Rep 6 , (2016)

McKenney, J. K., Desai, S., Cohen, C., Amin, M. B. Discriminatory immunohistochemical staining of urothelial carcinoma in situ and non-neoplastic urothelium: an analysis of cytokeratin 20, p53, and CD44 antigens. Am J Surg Pathol 25 (8), (2001)

Human epididymis protein 4 (HE4)

Kalapotharakos, G., Asciutto, C., Henic, E., et al. High preoperative blood levels of HE4 predicts poor prognosis in patients with ovarian cancer J Ovarian Res 5 (20), (2012)

CDKN2A/p16INK4a

Rambau, P. F., Vierkant, R. A., Intermaggio, M. P., et al. Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study J Pathol Clin Res 4 (4),250-261 (2018)

Estrogen receptor alpha

Chen, S., Dai, X., Gao, Y., et al. The positivity of estrogen receptor and progesterone receptor may not be associated with metastasis and recurrence in epithelial ovarian cancer Sci Rep 7 (1), (2017)

Human epidermal growth factor receptor 2 (HER2)

Luo, H., , Xu, X.,, et al. The prognostic value of HER2 in ovarian cancer: A meta-analysis of observational studies. PLoS One 13 (1), (2018)

Teplinksy, E., Muggia, F. EGFR and HER2: is there a role in ovarian cancer? Trans Cancer Res 4 (1),107-117 (2015)

Osteopontin

Hu, Z. D., Weiwie, T. T., Yang, M., et al. Diagnostic value of osteopontin in ovarian cancer: a meta-analysis and systematic review PLoS One 10 (5), (2015)

Zhao, H., Chen, Q., Alam, A., et al. The role of osteopontin in the progression of solid organ tumour Cell Death Dis 9 (3),356 (2018)

Programmed cell death protein 1 (PD1)

Thangavelu, G., Anderson, C .C. An essential role for programmed death-1 in the control of autoimmunity: implications for the future of hematopoietic stem cell transplantation Future Oncol 7 (8),929-932 (2011)

Drakes, N. L., Mehrotra, S., Aldulescu, M., et al. Stratification of ovarian tumor pathology by expression of programmed cell death-1 (PD-1) and PD-ligand- 1 (PD-L1) in ovarian cancer J Ovarian Res 11 (43), (2018)

Xue, C., Zhu, D., Chen, L., et al. Expression and prognostic value of PD-L1 and PD-L2 in ovarian cancer Trans Cancer Res 8 (1),111-119 (2019)

IGFBP2

Pickard, A., McCance, D. J. IGF-Binding Protein 2 - Oncogene or Tumor Suppressor? Front Endocrinol 6 (25), (2015)

Lee, E. J., Mircean, C., Shmulevich, I., et al. Insulin-like growth factor binding protein 2 promotes ovarian cancer cell invasion Mol Cancer 63 (11),2771-2774 (2005)

Kallikrein 8

Kishi, T., Grass, L., Soosaipillai, A., et al. Human kallikrein 8, a novel biomarker for ovarian carcinoma Cancer Res 63 (11), (2003)

Borgoño, C. A., Kishi, T., Scorilas, A. Human kallikrein 8 protein is a favorable prognostic marker in ovarian cancer Clin Cancer Res 12 (5),1487-1493 (2006)

Cytokeratin 7 CK7

Ramalingam, P., Malpica, A., Silva, E. G., et al. The use of cytokeratin 7 and EMA in differentiating ovarian yolk sac tumors from endometrioid and clear cell carcinomas Am J Surg Pathol 28 (11),1499-1505 (2004)

Vang, R., Gown, A. M., Barry, T. S., et al. Cytokeratins 7 and 20 in primary and secondary mucinous tumors of the ovary: analysis of coordinate immunohistochemical expression profiles and staining distribution in 179 cases Am J Surg Pathol 30 (9),1130-1139 (2006)

Cytokeratin 20 (CK20)

Taylor, J., McCluggage, W. G. Ovarian seromucinous carcinoma: report of a series of a newly categorized and uncommon neoplasm Am J Surg Pathol 39 (7),983-992 (2015)

Pan-cytokeratin

Goel, A., Mohan Rao, N., Santhi, V., et al. Immunohistochemical Characterization of Normal Ovary and Common Epithelial Ovarian Neoplasm with a Monoclonal Antibody to Cytokeratin and Vimentin Iran J Pathol 13 (1),23-29 (2018)

Vimentin

Forkhead box L2 (FOXL2)

Kommoss, S., Anglesio, M. S., Mackenzie, R., et al. FOXL2 molecular testing in ovarian neoplasms: diagnostic approach and procedural guidelines Mod Pathol 26 (6),860-867 (2013)

McCluggage, W. G., Singh, N., Kommoss, S., et al. Ovarian cellular fibromas lack FOXL2 mutations: a useful diagnostic adjunct in the distinction from diffuse adult granulosa cell tumor Am J Surg Pathol 37 (9),1450-1455 (2013)

ARID1A

Mao, T. L., Ardighieri, L., Ayhan, A., et al. Loss of ARID1A expression correlates with stages of tumor progression in uterine endometrioid carcinoma Am J Surg Pathol 37 (9),1342-1348 (2013)

Huang, H. N., Lin, M. C., Huang, W. C., et al. Loss of ARID1A expression and its relationship with PI3K-Akt pathway alterations and ZNF217 amplification in ovarian clear cell carcinoma Mod Pathol 27 (7),983-990 (2014)

Samartzis, E. P., Noske, A., Dedes, K. J., et al. ARID1A mutations and PI3K/AKT pathway alterations in endometriosis and endometriosis-associated ovarian carcinomas Int J Mol Sci 14 (9),18824-18829 (2013)

Xiao, W., Awadallah, A., Xin, W. Loss of ARID1A/BAF250a expression in ovarian endometriosis and clear cell carcinoma Int J Clin Exp Pathol 5 (7),642-650 (2012)