title: Immunohistochemical detection of hMLH1 and hMSH2 proteins in vulvar carcinoma.
abstract: The immunohistochemical (IHC) detection of MMR proteins is an accurate and rapid method to predict the presence of defective DNA MMR genes. MMR protein expression could also serve as a prognostic indicator of human cancers. The results of many studies demonstrate the usefulness of IHC tests with monoclonal antibodies MSH2 and MLH1 in screening the microsatellite sequence instability within both spontaneous and hereditary malignant neoplasms. The aim of our study was to perform an IHC estimation of the hMLH1 and hMSH2 expression in a subset of vulvar carcinomas according to HPV 16/18 status. The level of MMR proteins was further analyzed in relation to histoclinical features of the disease in either HPV-positive or -negative cancers. We identified archival diagnostic phase tissue specimens from 46 cases of vulvar cancer. From the same paraffin blocks containing material from the margin of surgical section during vulvectomy, normal epithelial tissue fragments were collected and designated as the control group. The characteristic of the lesion was examined in comparison with the presence of HPV DNA. Identification of the HPV 16/18 types was performed using PCR. IgG1 monoclonal antibodies detecting those epitopes characteristic for hMLH1 and hMSH2 were used in the study. In the analyzed cases of vulvar cancer, we have observed increased expression of proteins of both hMSH2 and hMLH1 genes compared to the control group. A comparison of the hMLH1 and hMSH2 protein expression levels showed that hMSH2 expression was higher than that of hMLH1 in the case of vulvar carcinomas. The performed analysis of correlation between individual parameters did not reveal statistically significant relationship with both the gradient and status of HPV 16/18. hMSH2 and hMLH1 were definitely interrelated.
authors.affiliation: Clinic I of Obstetrics and Gynecology, Skubiszewski University School of Medicine, ul. Staszica, 20-081 Lublin, Poland. annakwa@eskulap.am.lublin.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Kwasniewska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Postawski
authors.forename: Anna
authors.initials: A
authors.lastname: Gozdzicka-Józefiak
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Zdunek
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Korobowicz
authors.forename: Roman
authors.initials: R
authors.lastname: Miturski
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000939:Epitopes; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics; D011044:Poland; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D014846:Vulvar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D000939:Epitopes; 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