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Expressional analysis of MLH1 and MSH2 in breast cancer

Authors :
Nosheen Masood
Jahangir Sarwar Khan
Saima Shakil Malik
Parvez Ahmed
Zafar Ullah Shah
Muhammad Asif
Source :
Current Problems in Cancer. 43:97-105
Publication Year :
2019
Publisher :
Elsevier BV, 2019.

Abstract

Background Mismatch repair proteins are ubiquitous keys in diverse cellular functions and protects the genome by correcting mismatch as post replication error correction machinery. Mismatch repair deficiency was associated with tumor development and progression therefore, current study was aimed to investigate MLH1 and MSH2 expression in breast cancer and correlate patients' clinicopathological factors with status of mismatch repair genes. Material and methods Breast cancer tissues with adjacent normal tissue along with clinical details were collected during surgery from 80 cases. Immunohistochemistry was performed with primary and secondary antibodies for expressional analysis. Results were analyzed using SPSS version 24. Results Immunohistochemical analysis revealed that both MLH1 and MSH2 were crucial in maintaining DNA repair system and loss of these 2 mismatch repair proteins may lead to adverse outcomes in breast cancer. Statistically significant association was found between loss of MLH1 (P = 0.0004; odds ratio 13.8; 95% confidence interval 4.6-41.1), MSH2 (P = 0.0002; odds ratio 14.0; 95% confidence interval 4.7-42.2) and breast cancer. Statistical analysis demonstrated that MLH1 and MSH2 deficiency may lead breast cancer progression to advanced stage, correlated with tumor focality (MLH1 P = 0.001; MSH2 P = 0.002) and chemotherapy (MLH1 P = 0.01; MSH2 P = 0.04). Presence of CK7, GATA 3, and E cadherin tends to increase in mismatch repair deficient breast cancer. Whereas, no association of mismatch repair deficiency was observed with age, tumor grade, positive lymph nodes, menopause, and ER and/or PR status. Conclusion Loss of mismatch repair proteins in breast cancer highlights its potential role in DNA repair mechanisms and helps tumor cells to become resistant against chemotherapeutic drugs. Therefore, mismatch repair deficiency may contribute to breast cancer progression.

Details

ISSN :
01470272
Volume :
43
Database :
OpenAIRE
Journal :
Current Problems in Cancer
Accession number :
edsair.doi.dedup.....45c33559b9995c1a18b517dc4956f8b4
Full Text :
https://doi.org/10.1016/j.currproblcancer.2018.08.001