Kushnir Vladimir M, Nalbantoglu Ilke, Watson Rao, Goodwin Jonathan, Safar Elyas, Chokshi Reena V, Azar Riad R, Davidson Nicholas O
Division of Gastroenterology, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8124, St Louis, MO, 63110, USA,
Dig Dis Sci. 2014 Nov;59(11):2757-64. doi: 10.1007/s10620-014-3245-9. Epub 2014 Jun 13.
The presence of advanced adenomas in younger individuals is a criterion for Lynch syndrome (LS). However, the utility of screening advanced adenomas for loss of mismatch repair (MMR) protein expression to identify suspected LS remains unclear.
Determine the prevalence of MMR defects to understand whether these patients harbor a defined genetic risk for CRC.
The study cohort included adult patients ≤45 years of age with advanced adenomas (villous histology, ≥1 cm in diameter, ≥3 polyps of any size) endoscopically removed between 2001 and 2011. Clinical records were reviewed along with detailed pathological review and immunohistochemical MMR analysis.
A total of 76 (40.1 % male, age 40.6 ± 5.4 years) patients met inclusion and exclusion criteria. Indications for colonoscopy were gastrointestinal (GI) bleeding 39 (51.3 %), CRC in a first-degree relative 17 (22.4 %) and somatic GI symptoms 20 (26.3 %). Index colonoscopy revealed a median of 1 adenoma (range 1-4), mean diameter of 12.9 ± 7.1 mm, 40 (52.6 %) with villous histology. The mean follow-up duration was 3.3 ± 2 years. Recurrent adenomas developed in 24 (31.6 %), of which 8 (10.5 %) were advanced adenomas; none of these patients developed CRC. One of 66 (1.5 %) adenomas available for immunohistochemical (IHC) testing revealed loss of MLH1 and PMS2.
IHC screening of advanced adenomas from patients younger than 45 years of age identified potential LS in one of 64 patients. The low yield of IHC screening in this population suggests that universal IHC screening of advanced adenomas from patients younger than 45 years of age for MMR defects is not an efficient strategy for identifying LS subjects.
年轻个体中存在晚期腺瘤是林奇综合征（LS）的一项标准。然而，通过筛查晚期腺瘤的错配修复（MMR）蛋白表达缺失来识别疑似LS的效用仍不明确。
确定MMR缺陷的患病率，以了解这些患者是否存在明确的结直肠癌（CRC）遗传风险。
研究队列包括2001年至2011年间通过内镜切除的年龄≤45岁的晚期腺瘤（绒毛状组织学、直径≥1 cm、任何大小的息肉≥3个）成年患者。回顾了临床记录，并进行了详细的病理检查和免疫组化MMR分析。
共有76例（40.1%为男性，年龄40.6±5.4岁）患者符合纳入和排除标准。结肠镜检查的指征为胃肠道（GI）出血39例（51.3%）、一级亲属患CRC 17例（22.4%）和躯体GI症状20例（26.3%）。首次结肠镜检查发现腺瘤的中位数为1个（范围1 - 4个），平均直径为12.9±7.1 mm，40例（52.6%）为绒毛状组织学。平均随访时间为3.3±2年。24例（31.6%）出现复发性腺瘤，其中8例（10.5%）为晚期腺瘤；这些患者均未发生CRC。66例可进行免疫组化（IHC）检测的腺瘤中有1例显示MLH1和PMS2缺失。
对45岁以下患者的晚期腺瘤进行IHC筛查，在64例患者中发现1例潜在的LS。该人群中IHC筛查的低阳性率表明，对45岁以下患者的晚期腺瘤进行普遍的MMR缺陷IHC筛查并非识别LS患者的有效策略。
