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, beta-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, beta-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 demonstrates 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.

Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer syndromes / Losi, Lorena; Di Gregorio, C; Pedroni, Monica; Ponti, Giovanni; Roncucci, Luca; Scarselli, A; Genuardi, M; Baglioni, S; Marino, M; Rossi, G; Benatti, Piero; Maffei, S; Menigatti, M; Roncari, Barbara; PONZ DE LEON, Maurizio. - In: THE AMERICAN JOURNAL OF GASTROENTEROLOGY. - ISSN 0002-9270. - STAMPA. - 100:10(2005), pp. 2280-2287. [10.1111/j.1572-0241.2005.00223.x]

Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer syndromes

LOSI, Lorena;PEDRONI, Monica;PONTI, Giovanni;RONCUCCI, Luca;BENATTI, Piero;RONCARI, Barbara;PONZ DE LEON, Maurizio
2005

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, beta-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, beta-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 demonstrates 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.
2005
100
10
2280
2287
Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer syndromes / Losi, Lorena; Di Gregorio, C; Pedroni, Monica; Ponti, Giovanni; Roncucci, Luca; Scarselli, A; Genuardi, M; Baglioni, S; Marino, M; Rossi, G; Benatti, Piero; Maffei, S; Menigatti, M; Roncari, Barbara; PONZ DE LEON, Maurizio. - In: THE AMERICAN JOURNAL OF GASTROENTEROLOGY. - ISSN 0002-9270. - STAMPA. - 100:10(2005), pp. 2280-2287. [10.1111/j.1572-0241.2005.00223.x]
Losi, Lorena; Di Gregorio, C; Pedroni, Monica; Ponti, Giovanni; Roncucci, Luca; Scarselli, A; Genuardi, M; Baglioni, S; Marino, M; Rossi, G; Benatti, ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/760469
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