MCM2 Expression in Different Molecular Subtypes of Epithelial Breast Cancers and its Association with Clinicopathological Parameters and Ki-67 Expression

Abstract

Introduction: Breast cancer is one of the most common malignancies, with few subtypes having a more aggressive outcome and resistance to conventional therapies, Triple Negative Breast Cancers (TNBCs) being one such variant. The Ki-67 lacks reproducibility and a standardised cut-off. MCM2 (Minichromosome Maintenance 2) has role in DNA repair and replication and its role as alternate marker for prognosis has been studied in this case. Aim: To study MCM2 expression with respect to histologic grade, stage, nodal status and molecular subtypes of breast carcinoma. Also, to look for any correlation between Ki-67 and MCM2 expressions. Materials and Methods: A cross-sectional, observational study conducted on a group of 20 patients who underwent mastectomy in a Tertiary Care Centre, R.G. Kar Medical College and Hospital, Kolkata, West Bengal, India, for a total duration of six months. Histologic grading, staging, nodal status was evaluated from Haematoxylin and Eosin (H&E) stained sections. Formalin-Fixed Paraffin-Embedded (FFPE) blocks suitable for Immunohistochemistry (IHC) were selected and MCM2, Estrogen Receptor (ER), Human Epidermal Growth Factor Receptor 2 (HER2), Progesterone Receptor (PR)/neu and Ki-67 were performed. Scores given based on visual examination under light microscope. Analysis was done using IBM Statistical Package for the Social Sciences (SPSS) version 25.0 software. Results: Most of the subjects belonged to 41-55 years age group. Statistical significance was seen between high MCM2 and Ki- 67 expressions (p-value=0.0171) and high histologic grade and TNBCs (p-value=0.009). High MCM2 and Ki-67 expressions also come with increased risk for advanced disease. High Ki-67 is also a risk predictor for lymph node positive cases. Positive correlation was seen between MCM2 and (R)= 0.4318. Conclusion: The MCM2 is a predictor for adverse outcomes in breast carcinoma cases. It may serve as an alternative to Ki-67 as a proliferation marker, to guide clinicians in treatment strategies. Its role as a therapeutic target in aggressive breast carcinomas may be evaluated with larger study population in the future.