Poh Aaron, Chang Heidi Sian Ying, Tan Kok Yang, Sam Xin Xiu, Khoo Avery, Choo Shoa Nian, Nga Min En, Wan Wei Keat
Department of General Surgery, Khoo Teck Puat Hospital, Singapore.
University Surgical Cluster, National University Hospital, Singapore.
Singapore Med J. 2018 Mar;59(3):139-143. doi: 10.11622/smedj.2017012. Epub 2017 Feb 17.
Sporadic colorectal cancers with BRAF mutations constitute two distinct subgroups of colorectal cancers. Recent studies have linked the presence of the BRAF mutation to a familial inheritance pattern. This was a proof-of-concept study that aimed to examine: (a) the extent of field change in sporadic colorectal cancers with BRAF mutation; and (b) the extent of resection margins required and the pattern of DNA mismatch repair protein loss in these tumours.
Eight microsatellite instability-high tumours with positive BRAF mutation from an existing histopathological database were selected for BRAF mutation and mismatch repair protein analysis.
All the resection margins were negative for BRAF mutation. Three tumours had loss of MLH1 and PMS2 expressions, and five tumours had no protein loss. Six peritumoral tissues were negative and one was positive for BRAF mutation.
The results suggest that any early field change effect is restricted to the immediate vicinity of the tumour and is not a pan-colonic phenomenon. Current guidelines on resection margins are adequate for BRAF mutation-positive colorectal cancers. Any suggestion of a hereditary link to these tumours is likely not related to germline BRAF gene mutations. The pattern of protein loss reinforces previous findings for the two subgroups of BRAF mutation-positive colorectal cancers.
伴有BRAF突变的散发性结直肠癌构成了结直肠癌的两个不同亚组。最近的研究将BRAF突变的存在与家族遗传模式联系起来。这是一项概念验证研究,旨在探讨:(a)伴有BRAF突变的散发性结直肠癌中场效应改变的程度;以及(b)这些肿瘤所需的切缘范围和DNA错配修复蛋白缺失模式。
从现有的组织病理学数据库中选择8例BRAF突变阳性的微卫星高度不稳定肿瘤进行BRAF突变和错配修复蛋白分析。
所有切缘的BRAF突变均为阴性。3例肿瘤存在MLH1和PMS2表达缺失,5例肿瘤无蛋白缺失。6例肿瘤旁组织的BRAF突变为阴性,1例为阳性。
结果表明,任何早期场效应改变仅限于肿瘤紧邻区域,并非全结肠现象。目前关于切缘的指南适用于BRAF突变阳性的结直肠癌。这些肿瘤存在遗传联系的任何迹象可能与种系BRAF基因突变无关。蛋白缺失模式强化了先前关于BRAF突变阳性结直肠癌两个亚组的研究结果。