Associations of defect mismatch repair genes with prognosis and heredity in sporadic colorectal cancer

Publication date: February 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 2
Author(s): L. Ghanipour, K. Jirström, M. Sundström, B. Glimelius, H. Birgisson
BackgroundMicrosatellite instability arises due to defect mismatch repair (MMR) and occurs in 10–20% of sporadic colorectal cancer. The purpose was to investigate correlations between defect MMR, prognosis and heredity for colorectal cancer in first-degree relatives.Material and methodsTumour tissues from 318 patients consecutively operated for colorectal cancer were analysed for immunohistochemical expression of MLH1, MSH2 and MSH6 on tissue microarrays. Information on KRAS and BRAF mutation status was available for selected cases.ResultsForty-seven (15%) tumours displayed MSI. No correlation was seen between patients exhibiting MSI in the tumour and heredity (p = 0.789). Patients with proximal colon cancer and MSI had an improved cancer-specific survival (p = 0.006) and prolonged time to recurrence (p = 0.037). In a multivariate analysis including MSI status, gender, CEA, vascular and neural invasion, patients with MSS and proximal colon cancer had an impaired cancer-specific survival compared with patients with MSI (HR, 4.32; CI, 1.46–12.78). The same prognostic information was also seen in distal colon cancer; no recurrences seen in the eight patients with stages II and III distal colon cancer and MSI, but the difference was not statistically significant.ConclusionNo correlation between MSI and heredity for colorectal cancer in first-degree relatives was seen. Patients with MSI tumours had improved survival.



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