title: Reduced expression of hMLH1 and hMSH2 gene products in high-grade hepatocellular carcinoma.
abstract: We performed an immunohistochemical analysis of 2 major DNA mismatch repair proteins, human Mut L homologue-1 (hMLH1) and human Mut S homologue-2 (hMSH2), in hepatocellular carcinoma (HCC) using 33 biopsied and 58 surgically resected specimens, as well as 30 samples from non-cancerous livers. In well-differentiated HCCs, the immunoreactivity for these antigens was well preserved, and the staining intensity was stronger compared to the surrounding liver tissues. However, among 41 moderately-differentiated and 9 poorly-differentiated HCCs of the resected cases, hMLH1- and hMSH2-positive cells were significantly reduced in 19 (38%) and 9 (18%) cases, respectively. In 9 resected tumors, the expression of both of these antigens was reduced. Moreover, in 41 tumors of differing histological grades, 10 and 5 tumors for hMLH1 and hMSH2, respectively, contained a less-differentiated area with a reduced number of immunoreactive cells. The samples from non-cancerous biopsied liver and fetal autopsy tissue were well immunostained for both hMLH1 and hMSH2. We confirmed in this series that the hMLH1 and hMSH2 defect did commonly occur in high-grade HCCs, and that it might play a role in tumor progression.
authors.affiliation: Department of Pathology I, Okayama University Medical School, Okayama 700-8558, Japan. yw7144@kchnet.or.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Wani
authors.forename: K
authors.initials: K
authors.lastname: Notohara
authors.forename: C
authors.initials: C
authors.lastname: Tsukayama
authors.forename: S
authors.initials: S
authors.lastname: Okada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D006528:Carcinoma, Hepatocellular / Q000737:chemistry* / Q000473:pathology; D002352:Carrier Proteins; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005260:Female; D005333:Fetus / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000196:embryology; D008113:Liver Neoplasms / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000032:analysis* / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein