Proximal colon cancer in patients aged 51-60 years of age should be tested for microsatellites instability. A comment on the revised bethesda guidelines

Purpose: The Bethesda guidelines suggest to perform microsatellite instability (MSI) test in early onset rectal cancer and not in patients >50 years with proximal colon cancer. The aim of the study was to evaluate whether the risk of high MSI (MSI-H) is greater in proximal colon cancer of patients 51-60 years old than in early-onset rectal cancer. Methods: Consecutive colorectal cancer (CRC) patients were evaluated. Tumor location, cancer family history, MSI status and histology were recorded. Mutations in MLH1/MSH2 were investigated in MSI-H tumors. Patients were subdivided into groups: group A, proximal colon cancer patients 51-60 years old and groups B, C and D, patients ≤-50 years old, with rectal cancer, proximal and distal colon cancer, respectively. Results: Out of 409 CRC patients evaluated, 48 (12%) showed tumors withMSI-H. No MSI-H tumors were found in distal and rectal tumors of patients at sixth decade of life. Group A included 27 patients, eight (29.7%) MSI-H cancers, four missense mutations in MLH1/MSH2; groups B, C and D included 26, 11 and 11 patients with two (7.7%), two (18%) and two (18%) MSI-H cancers, respectively. One missense mutation on MSH2 in group B, one pathogenetic mutation on MSH1 in group C and one pathogenetic mutation on MSH2 in group D were found. Tumors of group A showed an increased probability to have MSI-H if compared to those of group B (OD=4.907, p=0.043). Conclusions: The Bethesda criteria should be broadened to include patients 51-60 years old with proximal colon cancer.