Mismatch repair genes in renal cortical neoplasms.
Mutation of human mutL homolog 1 (MLH-1) and human mutS homolog 2 (MSH-2) has been linked with the pathogenesis of colorectal carcinoma in hereditary nonpolyposis colorectal cancer syndrome and other carcinomas. Mutations of these genes in renal cell carcinomas were recently described. The aim of this study was to examine the expression of MLH-1 and MSH-2 in renal cortical neoplasms of various histological types by immunohistochemistry. Thirty-eight (n = 38) resected renal tumors were obtained from the surgical pathology files of the UMass Memorial Healthcare, including clear cell carcinomas (CLEARs, n = 20), papillary carcinomas (PAPs, n = 8), chromophobe carcinomas (CHRs, n = 4), and oncocytomas (ONCs, n = 6). Positive immunostaining for MLH-1 and MSH-2 was graded by the number of positive tumor cell nuclei, as follows: 0, negative; 1, up to one third of positive nuclei; 2, one to two thirds positive; and 3, greater than two thirds positive. Loss of MLH-1 or MSH-2 was defined as a tumor with grade 0 or 1, compared with the normal tubules. Normal tubules and intercalated ducts contained cells positive for MLH-1 and MSH-2 in all cases. For both antibodies, positive staining in tumors ranged from grade 1 to 3 in the CLEAR and PAP but was only grade 2 to 3 in the CHR and ONC. Loss of MLH-1 and/or MSH-2 occurred in malignant tumors but not in ONC. Loss of MLH-1 was present in 8 (40%) of 20 CLEARs and 4 (50%) of 8 PAPs, compared with loss of MSH-2 in 4 (20%) of 20 CLEARs and 1 (25%) of 4 CHRs. Our results suggest that loss of mismatch repair genes is involved in the malignant transformation in some renal carcinomas, particularly those derived from the proximal tubules.
Baiyee
Daniel
D
Department of Pathology, Stanford University School of Medicine, CA 94305-5324, USA. debaiyee@yahoo.com
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Barbara
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D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D006801:Humans; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein