Background: Surveillance programs in families with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), which is an autossomal dominant disease, decrease colorectal carcinoma mortality. There are multiple clinical criteria for the identification of these families, mainly: the Amsterdam Criteria (ACI), the modified Amsterdam Criteria (ACII) and the Bethesda Guidelines (BG).
Aims: To correlate, in families with HNPCC, the clinical criteria with the probability of detecting a germ-line mutation in MLH1, MSH2 and MSH6 mismatch repair genes.
Methods: We included 92 affected patients belonging to different families. Clinical criteria leading to HNPCC diagnosis were evaluated. Germ-line mutations in MLH1, MSH2 and MSH6 genes were performed by DGGE/MLPA and direct sequencing.
Results: Germ-line mutations were detected in 54/92 (59%) families, 30 in MLH1, 23 in MSH2 and 1 in MSH6. Germ-line mutation detection was significantly lower in ACI without age criteria (0%), when compared to: ACI (60%), ACII (62%), ACII without age criteria (67%) and BG (61%).
Conclusions: The classic, modified AC and BG allowed the detection of an identical percentage of families with mutation positive HNPCC. The absence of the age criteria in the ACI makes the HNPCC diagnosis highly unlikely. Simpler and uniform criteria should be elaborated, to allow a homogeneous identification of families with HNPCC.