title: Microsatellite instability and MLH1 and MSH2 germline defects are related to clinicopathological features in sporadic colorectal cancer.
abstract: Clinical and pathological features were evaluated to predict tumor microsatellite instability (MSI) and germline mutations in MLH1 and MSH2 DNA mismatch repair genes in two patient groups with sporadic colorectal cancer (CRC): 38 young patients (age </=45 years) and 31 old patients (age >/=60 years). Nine (25.7%) young patients out of 35 and five (16%) old patients out of 31 exhibited MSI in their cancers. MSI+ cancers were related to proximal cancer and mucinous carcinoma independently of the age at cancer onset. Three (7.9%) out of 38 young patients had mutations in MLH1 and MSH2 genes that led to truncated protein products; they were all at age <35 years and showed MSI in their tumors, with mucinous histotype in two cases. In conclusion, histopathological and clinical features of CRC allow identification of cancers showing DNA microsatellite instability. MSI in CRC at very early onset (age <35 years) appears useful to predict germline MMR gene defects.
authors.affiliation: Department of Gastroenterology, Centro di Riferimento Oncologico, I-33081, Aviano (PN), Italy.
authors.forename: M
authors.initials: M
authors.lastname: Fornasarig
authors.forename: A
authors.initials: A
authors.lastname: Viel
authors.forename: M
authors.initials: M
authors.lastname: Valentini
authors.forename: E
authors.initials: E
authors.lastname: Capozzi
authors.forename: R
authors.initials: R
authors.lastname: Sigon
authors.forename: A
authors.initials: A
authors.lastname: De Paoli
authors.forename: L
authors.initials: L
authors.lastname: Della Puppa
authors.forename: M
authors.initials: M
authors.lastname: Boiocchi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004260:DNA Repair; D004268:DNA-Binding Proteins; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / 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