Original Contribution
The American Journal of Gastroenterology (2005) 100, 2280–2287; doi: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
Lorena Losi MD1, Carmela Di Gregorio MD4, Monica Pedroni PhD2, Giovanni Ponti MD2, Luca Roncucci MD2, Alessandra Scarselli PhD2, Maurizio Genuardi MD3, Silvana Baglioni PhD3, Massimiliano Marino PhD2, Giuseppina Rossi MD2, Piero Benatti MD2, Stefania Maffei PhD2, Mirco Menigatti MD2, Barbara Roncari PhD2 and Maurizio Ponz de Leon MD2
- 1Departments of Pathology, University of Modena and Reggio, Emilia, Italy
- 2Internal Medicine, University of Modena and Reggio, Emilia, Italy
- 3Department of Clinical Physiopathology, Section of Medical Genetic, University of Firenze, Italy
- 4Service of Pathology, Hospital of Carpi, Italy
Correspondence: Lorena Losi, Dipartimento di Anatomia Patologica e di Medicina Legale, Sezione di Anatomia Patologica, Via del pozzo 71, 41100 Modena, Italy
Received 19 March 2005; Revised 0000; Accepted 20 May 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, 
-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, -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.
