MCM2: An alternative to Ki-67 for measuring breast cancer cell proliferation.

Abstract

Breast cancer is a heterogeneous disease comprising a diversity of tumor subtypes that manifest themselves in a wide variety of clinical, pathological, and molecular features. One important subset, luminal breast cancers, comprises two clinically distinct subtypes luminal A and B each of them endowed with its own genetic program of differentiation and proliferation. Luminal breast cancers were operationally defined as follows: Luminal A: ER+, PR+, HER2-, Ki-67<14% and Luminal B: ER+ and/or PR+, HER2-,Ki-67≥14% or, alternatively ER+ and/or PR+, HER2+, any Ki-67. There is currently a need for a clinically robust and validated immunohistochemical assay that can help distinguish between luminal A and B breast cancer. MCM2 is a family member of the minichromosome maintenance protein complex whose role in DNA replication and cell proliferation is firmly established. As MCM2 appears to be an attractive alternative to Ki-67, we sought to study the expression of MCM2 and Ki-67 in different histological grades and molecular subtypes of breast cancer focusing primarily on ER-positive tumors. MCM2 and Ki-67 mRNA expression were studied using in silico analysis of available DNA microarray and RNA-sequencing data of human breast cancer. We next used immunohistochemistry to evaluate protein expression of MCM2 and Ki-67 on tissue microarrays of invasive breast carcinoma. We found that MCM2 and Ki-67 are highly expressed in breast tumors of high histological grades, comprising clinically aggressive tumors such as triple-negative, HER2-positive and luminal B subtypes. MCM2 expression was detected at higher levels than that of Ki-67 in normal breast tissues and in breast cancers. The bimodal distribution of MCM2 scores in ER+/HER2- breast tumors led to the identification of two distinct subgroups with different relapse-free survival rates. In conclusion, MCM2 expression can help sorting out two clinically important subsets of luminal breast cancer whose treatment and clinical outcomes are likely to diverge.

• Authors: Einas M Yousef, Daniela Furrer, David L Laperriere, Muhammad R Tahir, Sylvie Mader, Caroline Diorio, Louis A Gaboury
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 30 Issue 5 Pg. 682-697 (05 2017) ISSN: 1530-0285 [Electronic] United States
• PMID: 28084344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Ki-67 Antigen
• MCM2 protein, human
• Minichromosome Maintenance Complex Component 2

Topics

• Biomarkers, Tumor (analysis)
• Breast Neoplasms (classification, mortality, pathology)
• Cell Proliferation
• Disease-Free Survival
• Female
• Humans
• Kaplan-Meier Estimate
• Ki-67 Antigen (analysis, biosynthesis)
• Minichromosome Maintenance Complex Component 2 (analysis, biosynthesis)
• Neoplasm Grading (methods)