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The Prognostic Value of Deficient Mismatch Repair in Stage II–IVa Nasopharyngeal Carcinoma in the Era of IMRT

Fang‐Ming Chen, Yunxiang Zhang, Xiufeng Li, Jianfang Gao, Hao Ma, Xiaoli Wang, Yang Li, Cheng Li, Yanan Zhang, Yating Zhang, Hongxing Kan, Han Li, Shigeng Zhang, Furong Hao, Mingchen Wang

2020Scientific Reports28 citationsDOIOpen Access PDF

Abstract

In the era of intensity-modulated radiotherapy (IMRT), it is important to analyse the prognostic value of deficient mismatch repair (dMMR) in nasopharyngeal carcinoma (NPC). In this study, in pretreatment biopsies of 69 patients with stage II-IVa NPC, the expression levels of MMR proteins, including MLH1, MSH2, MSH6 and PMS2, were assessed by immunohistochemistry (IHC). The median follow-up time was 37.5 months (3.1-87.4 months). 50.7% of cases (35/69) showed preserved expression of all 4 MMR proteins, which was interpreted as proficient mismatch repair (pMMR). Only 1.5% of cases (1/69) lost expression of all 4 MMR proteins, 26.1% of cases (18/69) have PMS2 loss alone and 21.7% of cases (15/69) lost expression of both PMS2 and MLH1. Thus, 49.3% of cases (34/69) lost expression of one or more MMR proteins, which was interpreted as dMMR. There was no significant difference (P > 0.05) in terms of sex, age, clinical stage, T category, N category or therapy regimens between the dMMR and pMMR groups. The multivariate Cox regression analysis revealed that dMMR was an independent significant prognostic factor for distant metastasis-free survival (DMFS) (dMMR vs pMMR: P = 0.01, HR = 0.25, 95% CI: 0.09~0.75). Therefore, NPC patients with dMMR had significantly superior DMFS compared with patients with pMMR. It can be expected that dMMR will become a new independent prognostic factor for NPC.

Topics & Concepts

PMS2MSH6MSH2MLH1Nasopharyngeal carcinomaMedicineOncologyInternal medicineImmunohistochemistryStage (stratigraphy)Proportional hazards modelDNA mismatch repairRadiation therapyCancerBiologyColorectal cancerPaleontologyGenetic factors in colorectal cancerLung Cancer Treatments and MutationsCholangiocarcinoma and Gallbladder Cancer Studies