Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
Hum Pathol. 2013 Nov;44(11):2518-28. doi: 10.1016/j.humpath.2013.06.012. Epub 2013 Sep 10.
The optimal strategy for screening patients with colorectal carcinoma for Lynch syndrome (LS) is a subject of continued debate in the literature with some advocating universal screening while others arguing for selective screening. We evaluated 1292 colorectal carcinomas for DNA mismatch repair protein abnormalities and identified 150 (11.6%) tumors demonstrating high-levels of microsatellite instability (MSI-H). MSI-H colorectal carcinomas were divided into sporadic (112/1292, 8.7%) and LS/probable LS-associated (38/1292, 2.9%) groups based on BRAF V600E mutation, MLH1 promoter hypermethylation, cancer history, and germline mismatch repair gene mutation. All MSI-H colorectal carcinomas were analyzed for grade, location, and tumor histology. The utility of the revised Bethesda guidelines and published predictive pathology models for MSI-H colorectal carcinomas (PREDICT and MSPath) were evaluated. Left-sided MSI-H colorectal carcinomas were more frequently associated with LS compared with right-sided MSI-H colorectal carcinomas (12/21, 57% versus 26/129, 20%, P = .0008). There was no significant difference in histology between sporadic MSI-H and LS/probable LS-associated colorectal carcinomas except for a slightly higher proportion of sporadic MSI-H tumors demonstrating tumor-infiltrating lymphocytes (81% versus 61%, P = .015). Neither pathology predictive model identified all LS-associated colorectal carcinomas (PREDICT: 33/38, 87%; MSPath: 35/38, 92%). 12/117 (10%) MSI-H colorectal carcinomas identified in patients >60 years were LS/probable LS-associated. Our results demonstrate that models of predicting MSI-H fail to identify LS-associated colorectal carcinoma given their reliance on right-sided location. A significant proportion (32%) of LS-associated colorectal carcinoma is identified in patients >60 years. Finally, our results demonstrate similar morphologic features between LS-associated and sporadic MSI-H colorectal carcinomas.
我们评估了 1292 例结直肠癌患者的 DNA 错配修复蛋白异常情况，发现 150 例（11.6%）肿瘤表现出高水平微卫星不稳定（MSI-H）。根据 BRAF V600E 突变、MLH1 启动子超甲基化、癌症病史和种系错配修复基因突变，将 MSI-H 结直肠癌分为散发性（112/1292，8.7%）和 LS/可能与 LS 相关（38/1292，2.9%）组。所有 MSI-H 结直肠癌均分析了分级、位置和肿瘤组织学。评估了修订后的贝塞斯达指南和发表的 MSI-H 结直肠癌预测病理学模型（PREDICT 和 MSPath）的实用性。评估了左 MSI-H 结直肠癌与右 MSI-H 结直肠癌相比更常与 LS 相关（12/21，57%比 26/129，20%，P=0.0008）。散发性 MSI-H 和 LS/可能与 LS 相关的结直肠癌之间除了散发性 MSI-H 肿瘤显示肿瘤浸润淋巴细胞的比例略高（81%比 61%，P=0.015）外，组织学无明显差异。两种病理学预测模型均未识别所有 LS 相关的结直肠癌（PREDICT：33/38，87%；MSPath：35/38，92%）。在>60 岁的患者中发现的 117 例 MSI-H 结直肠癌中有 12 例（10%）为 LS/可能与 LS 相关。我们的结果表明，由于依赖于右侧位置，预测 MSI-H 的模型无法识别 LS 相关的结直肠癌。LS 相关结直肠癌有相当大的比例（32%）发生在>60 岁的患者中。最后，我们的结果表明 LS 相关和散发性 MSI-H 结直肠癌之间具有相似的形态特征。
