MSH2 Loss in Primary Prostate Cancer.

摘要: Purpose: Inactivation of mismatch repair (MMR) genes may predict sensitivity to immunotherapy in metastatic prostate cancers. We studied primary tumors with MMR defects.Experimental Design: A total 1,133 prostatic adenocarcinomas and 43 small cell carcinomas (NEPC) were screened by MSH2 immunohistochemistry confirmation next-generation sequencing (NGS). Microsatellite instability (MSI) was assessed PCR NGS (mSINGS).Results: Of NEPC, 1.2% (14/1,176) had loss. Overall, 8% (7/91) Gleason pattern 5 (Gleason score 9-10) loss compared 0.4% (5/1,042) any other scores (P < 0.05). Five percent (2/43) NEPC generally homogenously lost, suggesting it an early/clonal event. confirmed loss-of-function alterations all (12/12) samples, biallelic inactivation 83% (10/12) hypermutation (10/12). 61% (8/13) 58% (7/12) patients definite MSI mSINGS, respectively. Three (25%) germline mutations Tumors a higher density infiltrating CD8+ lymphocytes grade-matched controls without (390 vs. 76 cells/mm2; P = 0.008), correlated mutation burden among cases (r 0.72, 0.005). T-cell receptor on subset revealed trend toward clonality versus controls.Conclusions: Loss protein is inactivation, hypermutation, tumor-infiltrating lymphocyte density, appears most common very high-grade tumors, for which routine screening be warranted if validated additional cohorts. Clin Cancer Res; 23(22); 6863-74. ©2017 AACR.