Differential diagnostics of hereditary colorectal cancer syndromes

One third of colorectal carcinomas (CRC) show familial clustering of which about 5% have a monogenetic trait. Distinction between disease with and without polyposis, tumor histology and tumor spectrum in a given patient are all of diagnostic relevance. Familial adenomatous polyposis (FAP) underlies approximately 1% of CRC characterized by rapidly forming (> 100) adenomas. In contrast to these about 2%-3% of CRC have a hereditary background without polyposis (HNPCC). This is the only hereditary tumour syndrome to date for which a tissue-based molecular screening test is available. Accordingly, expression analysis of mismatch repair genes (MSH2, MSH6 and MLH1, PMS2) is performed first. In the case of an equivocal result with no complete loss of expression testing of microsatellite instability (MSI) is added. In contrast to the other diseases MYH-associated polyposis (MAP) follows a recessive trait with polyp numbers usually between 15-30 adenomas and should be distinguished from attenuated forms of FAP with < 100 polyps in the differential diagnosis. In the case of suspected familial cancer syndrome genetic counseling is warranted in order to decide ultimately whether there is an indication for genetic testing (evidence of a germ-line mutation).