Mismatch Repair Protein Deficiency in Triple Negative Breast Carcinomas: Clinicopathological Features

Abstract

Abstract Introduction/Objective Female breast cancer has now surpassed lung cancer as the most commonly diagnosed cancer worldwide. Triple-negative breast cancer (TNBC) accounts for approximately 10–15% of all breast cancers. Chemotherapy remains the mainstay of systemic treatment for patients with TNBCs. Studies of mismatch repair (MMR) deficiency in TNBC reported variable prevalence ranging, from 0.2% to 18.6%. Recent studies described an excellent response in a patient with metastatic breast cancer treated with anti-PD1 illustrating the urgent need to test for MMRP deficiency as a predictive biomarkers to select those patients who could benefit from immunotherapy. The aim of the study is to detect MMRP deficiency in a cohort of TNBC Jordanian patients using the immunohistochemical methods. Methods/Case Report This study targeted cases of TNBC diagnosed and treated at King Hussein Cancer Center from 2015 until 2021. Clinicopathological data was obtained from 152 patients’ records. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins were performed on paraffin embedded tissue containing carcinoma. Results (if a Case Study enter NA) The median age of patients at diagnosis was 49 years. A total of 14 out of 152 (9.2%) cases showed deficient MMR (dMMR) expression. Loss of expression of PMS2 was seen in 13 cases, 5 of which showed also loss of MLH1 expression. Loss of expression of both MSH6 and MSH2 was seen in one case. Positive family history of cancer was present in 5 of 12 patients with available data, three of whom had isolated loss of PMS2 and two had combined loss of PMS2 and MLH1. One pt. with loss of MSH6 and MSH2, had a personal history of a second malignancy (Lung cancer). The median duration of follow-up was 27 months. The overall (OS) and event- free survival (EFS) were better for dMMR despite the lack of statistically significant differences. At 24 months EFS and OS were 77.9% and 85.7% for dMMR and 63.9% and 56.9% for pMMR respectively. Conclusion The prevalence of dMMR in TNBC is 9% with most of the cases apparently related to Lynch syndrome. dMMR tumors tend to be associated with better outcomes compared to pMMR cases. dMMR can serve as a biomarker for better prognosis. These results are of value in directing the clinical management.