Proliferation proteins

Another method to study cell proliferation is by looking at specific proteins that are expressed in proliferating cells, but absent from non-proliferating cells. This requires the use of specific primary antibodies against the antigens expressed during proliferation.

These antigens are typically expressed in the perinuclear or nuclear interior regions across all cell cycle phases except G0, making them excellent cellular markers for proliferation. Ki67 is a very popular proliferation marker and is routinely used in pathology labs due to its diagnostic and prognostic power in cancer. PCNA is another common marker, yet multiple studies have shown that Ki67 is more sensitive and specific when evaluating cell proliferation in tumors from various origins^3–6. A maker growing in prominence is MCM-2, and recent work suggests this may be a better choice for informing cancer prognoses than Ki67 and PCNA^7,8.

However, much of the data is inconclusive regarding a ‘best’ maker of proliferation, especially in a clinical context.

These immunoassays are excellent for fixed tissue samples and analysis by IHC.

• Accurate and reliable
• Large body of supporting data
• Clinical diagnostic and prognostic value in some cases

• Limited high-throughput options
• Scoring of results can be subjective
• Conflicting data around the ‘best’ marker of cell proliferation in a clinical setting

PCNA

• Proliferating cell nuclear antigen (PCNA) is expressed mainly in late G1 and S, to a lesser extent in S and G2, and is low or absent in G0 and early G1
• Widely used general cell proliferation marker⁹
• Reported prognostic significance in certain cancers
• Results relate only the number of proliferating cells, not the rate of proliferation

Immunohistochemical analysis of frozen sections from adult zebrafish intestine, labeled with an anti-PCNA antibody [PC10] (ab29).

Ki67

• Ki67 nuclear antigen is expressed in the cell cycle phases G1, S, G2 and M, but is absent in G0
• Ki67 index is widely used as a tumor marker in research and pathology
• Prognostic and diagnostic value in many cancers⁹
• Ki67 index correlates with the course of neoplastic disease and can be used to assess patient survival and cancer progression
• Results relate only the number of proliferating cells, not the rate of proliferation
• Often more specific than PCNA⁶

Immunohistochemical analysis of formalin/PFA-fixed paraffin-embedded sections from mouse spleen, labeled using an anti-Ki67 antibody (ab15580).

MCM-2

• MCM-2 plays a major role in DNA replication during G1, and is expressed throughout all phases except for G0
• Widely used as a proliferation marker
• Prognostic value in certain cancers
• May be a better than Ki67 to evaluate the progression of some cancers in certain cases^7,8,10

Immunohistochemical analysis of formalin/PFA-fixed paraffin-embedded sections from human small cell lung cancer tissue, labeled with an anti-MCM2 antibody (ab4461).