title: Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences.
abstract: Alterations of DNA mismatch repair (MMR) genes are involved in carcinogenesis of sporadic and inherited human cancers characterised by instability of DNA microsatellite sequences (MSI). MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunohistochemistry was tested in order to evaluate the utility of this method in predicting MMR deficiency. Colorectal (72), gastric (68), endometrial (44) and ovarian (17) carcinomas were independently evaluated for familial history, histological type of tumour, MSI status and immunohistochemical results. Loss of expression of either hMLH1 or hMSH2 was observed in 51 of 55 (92.8%) MSI tumours, while 145 of 146 microsatellite stable (MSS) tumours expressed both the hMLH1 and hMSH2 gene products. Independently of tumour site, an overall agreement between immunohistochemical and molecular results was observed in 15 hereditary non-polyposis colorectal cancer-related tumours. Among sporadic tumours, only 2 of 60 colorectal and 2 of 66 gastric carcinomas, displaying MSI, expressed both hMLH1 and hMSH2 gene products. All 39 endometrial and 16 ovarian tumours presented a concordant molecular and immunohistochemical profile. These data show that immunohistochemistry is an accurate and rapid method to predict the presence of defective DNA MMR genes and to identify both sporadic and familial MSI tumours.
authors.affiliation: Department of Pathology, Hospital Fondazione Macchi, Varese, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Chiaravalli
authors.forename: D
authors.initials: D
authors.lastname: Furlan
authors.forename: C
authors.initials: C
authors.lastname: Facco
authors.forename: M G
authors.initials: MG
authors.lastname: Tibiletti
authors.forename: A
authors.initials: A
authors.lastname: Dionigi
authors.forename: B
authors.initials: B
authors.lastname: Casati
authors.forename: L
authors.initials: L
authors.lastname: Albarello
authors.forename: C
authors.initials: C
authors.lastname: Riva
authors.forename: C
authors.initials: C
authors.lastname: Capella
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D003536:Cystadenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D004260:DNA Repair; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis*; D009687:Nuclear Proteins; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004273:DNA, Neoplasm; 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