Proximal colon cancer in patients aged 51–60 years of age should be tested for microsatellites instability. A comment on the Revised Bethesda Guidelines
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.
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.
Out of 409 CRC patients evaluated, 48 (12%) showed tumors with MSI-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).
The Bethesda criteria should be broadened to include patients 51–60 years old with proximal colon cancer.
KeywordsColorectal cancer Microsatellite instability Hereditary non-polyposis Colorectal cancer (HNPCC) Inherited gastrointestinal syndromes
Authors are grateful to Ms. Marina Canapero for her support in checking the linguistic accuracy of the paper, Mr. Ambrosi Alessandro, PhD, for the statistical analysis of the data and Dr. Giuseppe Gagliardi for his review of the manuscript. This work was supported in part by AIRC (Associazione Italiana Ricerca sul Cancro).
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