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Expressional analysis of MLH1 and MSH2 in breast cancer
- 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.
- Subjects :
- Adult
0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
DNA repair
medicine.medical_treatment
Breast Neoplasms
MLH1
03 medical and health sciences
0302 clinical medicine
Breast cancer
Internal medicine
medicine
Humans
Aged
Chemotherapy
business.industry
Carcinoma, Ductal, Breast
Odds ratio
Middle Aged
medicine.disease
MutS Homolog 2 Protein
030104 developmental biology
MSH2
030220 oncology & carcinogenesis
Immunohistochemistry
Female
DNA mismatch repair
MutL Protein Homolog 1
business
Subjects
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