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

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...

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Published in:	Scientific reports 2020-06, Vol.10 (1), p.9690-9690, Article 9690
Main Authors:	Chen, Fang-Ming, Zhang, Yun-Xiang, Li, Xiu-Feng, Gao, Jian-Fang, Ma, Hao, Wang, Xiao-Li, Li, Yang, Li, Cheng, Zhang, Ya-Nan, Zhang, Ya-Ting, Kan, Hong-Xing, Li, Han, Zhang, Shi-Geng, Hao, Fu-Rong, Wang, Ming-Chen
Format:	Article
Language:	eng
Subjects:	Adolescent Adult Aged Aged, 80 and over Biopsy Child Disease-Free Survival DNA Mismatch Repair - genetics DNA-Binding Proteins - metabolism Female Humans Immunohistochemistry Male Metastases Middle Aged Mismatch repair Mismatch Repair Endonuclease PMS2 - metabolism MLH1 protein MSH2 protein MSH6 protein MutL Protein Homolog 1 - metabolism MutS Homolog 2 Protein - metabolism Nasopharyngeal carcinoma Nasopharyngeal Carcinoma - diagnosis Nasopharyngeal Carcinoma - genetics Nasopharyngeal Carcinoma - pathology Nasopharyngeal Carcinoma - radiotherapy Nasopharyngeal Neoplasms - diagnosis Nasopharyngeal Neoplasms - genetics Nasopharyngeal Neoplasms - pathology Nasopharyngeal Neoplasms - radiotherapy Neoplasm Staging Prognosis Proteins Radiation therapy Radiotherapy, Intensity-Modulated Yeast Young Adult
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Summary:	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.
ISSN:	2045-2322 2045-2322