Mismatch repair enzyme expression in primary and castrate resistant prostate cancer  

作　　者：Belinda Nghiem Xiaotun Zhang Hung-Ming Lam Lawrence DTrue Ilsa Coleman Celestia SHigano Peter SNelson Colin CPritchard Colm Morrissey 

机构地区：[1]Department of Urology,University of Washington,Seattle,WA,USA [2]State Key Laboratory of Quality Research in Chinese Medicine,Macao Institute for Applied Research in Medicine and Health,Macao University of Science and Technology,Macao(SAR),China [3]Department of Pathology,University of Washington,Seattle,WA,USA [4]Divison of Human Biology,Fred Hutchinson Cancer Research Center,Seattle,WA,USA [5]Department of Medicine,University of Washington,Seattle,WA,USA [6]Department of Laboratory Medicine,University of Washington,Seattle,WA,USA

出　　处：《Asian Journal of Urology》2016年第4期223-228,共6页亚洲泌尿外科杂志（英文）

基　　金：We thank the patients and their families who were willing to participate in the Prostate Cancer Donor Program.The investigators Drs.Robert Vessella,Bruce Montgomery,Evan Yu,Heather Cheng,Elahe Mostaghel,Paul Lange,and Martine Roudier for their contributions to the University of Washington Medical Center Prostate Cancer Donor Rapid Autopsy Program;his research was supported by funding by the Pacific Northwest Prostate Cancer SPORE(P50CA97186),R01CA165573;the Richard M.LUCAS Foundation.Colm Morrissey is a recipient of a Career Development Award from Jim and Catherine Allchin.

摘　　要：Objective:Although the utility of immunohistochemistry(IHC)for assessing mismatch repair(MMR)protein expression has been demonstrated in solid tumors including primary prostate cancer(PCa),its utility has not been assessed in castration-resistant PCa(CRPC).Methods:Tissue microarrays were constructed from 127 radical prostatectomies and 155 CRPC metastases from 50 patients.MMR(MLH1,MSH2,MSH6,and PMS2)expression was assessed by IHC and gene expression arrays.Associations between MMR protein expression in PCa and CRPC and biochemical recurrence(BCR)or time from diagnosis to death respectively were determined.Results:There was no correlation between levels of MMR protein and BCR.Absence of MSH2 and MSH6 was the most pronounced at 15%and 22%in PCa and 17.8%and 16%in CRPC patients,respectively.MSH2 and MSH6 protein were absent in 9.4%and 8%of PCa and CRPC respectively.Absence of individual MMR proteins did not correlate with BCR or time from diagnosis to death.However absent MSH2/MSH6 in CRPC was associated with shorter time to death(pZ0.0006).Loss of MSH2 was verified at the gene expression level.This finding correlated with microsatellite instability previously reported in this CRPC cohort.

关 键 词：Mismatch repair Castration resistant prostate cancer MLH1 MSH2 MSH6 PMS2 

分 类 号：R73[医药卫生—肿瘤]