Prostate cancer with MMR gene mutation:a clinicopathological analysis of 16 cases
Purpose To summarize the clinicopathological features with DNA mismatch repair(MMR)gene mutation and to explore the correlation between MMR gene mutation and pro-tein expression in prostate cancer.Methods Clinicopathologi-cal data of 16 prostate cancer patients with MMR gene mutation were collected,the expression of four MMR proteins(MLH1,PMS2,MSH2,MSH6)was detected by immunohistochemical staining,and correlation was analyzed between MMR gene muta-tion and protein expression.Results The 16 patients age ranged from 55 to 79 years,with median 69 years.12 patients presented with distant metastasis that included 11 cases with bone metastasis and 1 case with multiple metastases.12 patients were castration-resistant prostate cancer(CRPC).The histologi-cal characteristic was mainly classical prostatic acinar adenocar-cinoma,including intraductal carcinoma(7 cases)and ductal adenocarcinoma(1 case).Nerve/vascular invasion and extra-prostatic extension were detected in 6 cases and 4 cases,respec-tively.The Gleason score of 14 patients was ≥8.Next genera-tion sequencing results revealed that MMR gene pathogenic mu-tations in 8 cases(including of 4 MSH2,3 MSH6,and 1 MLH3),and the variants of unknown clinical significance(VUS)of MMR gene in another 8 cases.Immunohistochemical results revealed that MMR protein expression was absent in only 5 out of the 14 cases,which included 2 MSH2 pathogenic muta-tions,2 MSH6 pathogenic mutations,and one VUS of MSH6 and MLH1.The matching rate of NGS and IHC in pathogenic mutations was 4/5,while in mutations of VUS was only 1/8.Conclusion The presence of MMR gene mutations in prostate cancer is commonly observed in cases with high Gleason grade,advanced clinical stage,and CRPC patients,often accompanied by intraductal carcinoma.The predominant MMR gene altera-tions identified in prostate cancer are MSH2 and MSH6 muta-tions.The mutation of the MMR gene and the loss of protein ex-pression in prostate cancer do not completely matched.
万方数据
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