RESUMEN
BACKGROUND: We previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated. METHODS: The Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Only path_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis. RESULTS: Ninety-nine path_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65 years of age or younger at diagnosis, and included 77 path_MLH1, 17 path_MSH2, and 2 path_MSH6 carriers. The number of cancers detected within < 1.5, 1.5-2.5, 2.5-3.5 and at > 3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5-3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectively (p < 0.001). Ten-year crude survival when the last colonoscopy had been < 1.5, 1.5-2.5, 2.5-3.5 or > 3.5 years before diagnosis, was 89, 90, 90 and 92%, respectively (p = 0.91). CONCLUSIONS: In path_MLH1 and path_MSH2 carriers, more advanced colon cancer stage was associated with poorer survival, whereas time since previous colonoscopy was not. Although the numbers are limited, together with our previously reported findings, these results may be in conflict with the view that follow-up of path_MMR variant carriers with colonoscopy intervals of less than 3 years provides significant benefit.
RESUMEN
BACKGROUND & AIMS: The risk for small bowel cancer (SBC) is significantly increased in hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC-associated SBCs are poorly characterized. METHODS: Thirty-two SBCs were characterized according to clinical, pathologic, and germline mutation data. Histomorphologic characteristics, microsatellite instability (MSI) testing, mismatch repair (MMR) protein expression, and frameshift mutations of 7 coding mononucleotide repeats were investigated in 17 SBCs. RESULTS: Median age at diagnosis was 39 years. Fifty percent of SBCs were located in the duodenum. The Amsterdam criteria were fulfilled in 50% of patients; 45% of patients had no personal history of previous malignancies. Two patients had a positive family history for SBC. Pathogenic germline mutations were identified in 81%; high MSI was detected in 95% and loss of MMR protein expression in 89% of cases. TGFBR2 , BAX , MSH3 , MSH6 , ACVR2 , AIM2 , and SEC63 frameshift mutations were detected in 69%, 59%, 59%, 35%, 82%, 56%, and 56%, respectively. An expansive growth pattern of the tumor border and an intense intratumoral lymphocytic infiltrate were present in 75%, respectively. CONCLUSIONS: HNPCC-associated SBC often manifests at a young age and may be the first disease manifestation. Endoscopy may detect 50% of tumors. Considering recent data on gastric cancer, we propose endoscopic screening of mutation carriers starting at 30 years of age because clinical criteria cannot define a high-risk group. In addition, our study shows that histopathologic criteria, MSI, and MMR immunohistochemistry are often similar to these features in HNPCC.
