This study aimed at defining the incidence, clinicopathological and molecular profile of the hereditary colorectal cancer (CRC) among the Macedonian population. During the past 2 year 192 (108 male, 76 female) randomly selected patients who had undergone colectomy at the Clinic of Abdominal Surgery in Skopje were enrolled in the study. Detailed questionnaire for family history , dietary and life-style habits were collected from each patient. DNA was isolated from peripheral blood and from fresh tumors obtained immediately after surgery from most of the patients. Paired tumor and blood DNA were analyzed for the presence of microsatellite (MSI) or chromosomal (CIN) instability phenotype using multiplex QPCR of 20 microsatellites located at 18q, 17p, 5p, 1p, 8p. The presence of Braf V600E mutations was analyzed in all MSI positive tumors by DNA sequencing, while MYH Y165T/G382A mutations were analyzed by PCR-RFLP in all patients with positive family history, <50 years of age or with multiple polyps/cancers at diagnosis.

Positive family history was present in 31 patient (16.1%) of which 1 patient has a clinical picture of AFAP syndrome, while the other 30 patients (17 male and 13 female) reported malignant disease in at least one family member. The average age in this group of patients (58.5y, range 28-81 years) was slightly lower than the average of the rest of the patients (63.2y). The distribution of Dukes stages at diagnosis and localization was similar with patients with sporadic tumors. Ten and 28 patients fulfilled the Amsterdam II and the revised Bethesda criteria, respectively, for clinical diagnosis of HNPCC. MSI was present in 4 out of 7 tumors from Amsterdam II and in non of 11 Bethesda families available for analysis. No Braf or MYH gene mutations were detected in any of the analyzed patients. Mutation analysis of MLH1 and MSH2 genes in patients with MSI tumors is in progress and will be reported at the conference.