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- Title
Molecular Genetic Alterations and Clinical Features in Early-Onset Colorectal Carcinomas and Their Role for the Recognition of Hereditary Cancer Syndromes.
- Authors
Losi, Lorena; Di Gregorio, Carmela; Pedroni, Monica; Ponti, Giovanni; Roncucci, Luca; Scarselli, Alessandra; Genuardi, Maurizio; Baglioni, Silvana; Marino, Massimiliano; Rossi, Giuseppina; Benatti, Piero; Maffei, Stefania; Menigatti, Mirco; Roncari, Barbara; de Leon, Maurizio Ponz
- Abstract
OBJECTIVES: Colorectal cancer (CRC) occurs rarely in young individuals (<45 yr) and represents one of the criteria for suspecting hereditary cancer families. In this study we evaluated clinical features and molecular pathways (chromosomal instability [CIN] and microsatellite instability [MSI]) in early-onset CRC of 71 patients. METHODS: Detailed family and personal history were obtained for each patient. Expression of APC, β-catenin, p53, MLH1, MSH2, and MSH6 genes was evaluated by immunohistochemistry. MSI analysis was performed and constitutional main mutations of the mismatch repair (MMR) genes were searched by gene sequencing. RESULTS: Fourteen (19.7%) out of the 71 cases showed both MSI and altered expression of MMR proteins. In the 57 MSI-negative (MSI−) lesions altered expression of APC, β-catenin, and p53 genes were found more frequently than in MSI-positive(MSI+) tumors. Seven (50%) out of the 14 patients with MSI+ tumors presented clinical features of Lynch syndrome (hereditary non-polyposis colorectal cancer [HNPCC]) and in all but one, constitutional mutations in MLH1 or MSH2 genes could be detected. The same mutations were also found in other family members. CONCLUSIONS: Our study demostrates the involvement of CIN in a majority of early-onset colorectal tumors. Furthermore, we identified Lynch syndromes in seven cases (50%) of early-onset colorectal carcinomas with impairment of the MMR system. These results suggest that patients with early-onset CRC should be screened for hereditary cancer syndrome through clinical and molecular characterizations.
- Subjects
COLON cancer; CANCER patients; GENETIC disorders; ONCOLOGY; TUMORS; IMMUNOHISTOCHEMISTRY
- Publication
American Journal of Gastroenterology (Springer Nature), 2005, Vol 100, Issue 10, p2280
- ISSN
0002-9270
- Publication type
Article
- DOI
10.1111/j.1572-0241.2005.00223.x