title: Microsatellite instability and hMLH1 and hMSH2 expression in renal tumors.
abstract: Defects in the function of mismatch repair (MMR) genes result in genetic instability, a common feature of malignant progression. This study was conducted to determine the frequency of genetic instability [defined as microsatellite instability (MSI)] and to evaluate the sensitivity/specificity of immunohistochemistry in predicting the deficiency in MMR genes in renal cortical tumors. A total of 51 surgically-resected renal tumors (27 clear cell, 10 papillary, 5 chromophobe carcinomas and 9 oncocytomas) were studied. We also analyzed the correlation with clinicopathological parameters, the MSI status (assessed by using 5 microsatellite markers: D2S123, D11S904, D3S1621, D3S1683 and BAT26), and the immunohistochemical expression of 2 major MMR genes [the human mutL homolog 1 (hMLH1) and the human mutS homolog 2 (hMSH2)]. Sixteen cases (31.4%) showed MSI: Three (5.9%) demonstrated a high level of MSI, 11 (21.6%) demonstrated a low level of MSI, 2 (3.9%) presented with a loss of heterozygosity, and the remaining 35 (68.6%) exhibited microsatellite stability. The loss of hMLH1 and hMSH2 immunohistochemical expressions was observed in 5/51 (9.8%) and 9/51 (17.6%) cases, respectively. The complete absence of both hMLH1 and hMSH2 immunohistochemical expressions was observed only in the 3 cases with a high level of MSI. This study showed that defects in MMR genes are involved in renal carcinogenesis and correlate with the occurrence of MSI.
authors.affiliation: Department of Diagnostic Medical Sciences and Special Therapies, University of Padova, 35100 Padova, Italy. giuseppe.altavilla@unipd.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Altavilla
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.forename: Graziella
authors.initials: G
authors.lastname: Busatto
authors.forename: Martina
authors.initials: M
authors.lastname: Orsolan
authors.forename: Luciano
authors.initials: L
authors.lastname: Giacomelli
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D042282:Microdissection; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein