Colorectal Tumors From Different Racial and Ethnic Minorities Have Similar Rates of Mismatch Repair Deficiency
Colorectal Tumors From Different Racial and Ethnic Minorities Have Similar Rates of Mismatch Repair Deficiency
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DOI：
10.1016/j.cgh.2016.03.037
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发表时间：
2016-08-01
影响因子：
12.6
通讯作者：
Sussman, Daniel A.
中科院分区：
文献类型：
--
作者：
Berera, Shivali;Koru-Sengul, Tulay;Sussman, Daniel A.
背景与目的：结直肠癌细胞中的微卫星不稳定性（MSI）是由错配修复（MMR）蛋白功能缺陷引起的，无论是获得性的还是来自种系改变，如Lynch综合征患者。林奇综合征的普遍筛查倡议得到了鼓励。然而，鲜为人知的是真正的患病率MMR缺陷和MSI在结直肠肿瘤的个人从不同的种族和民族亚组或其临床效果在这些population.METHODS：我们进行了回顾性分析，253例手术切除，原发性结直肠腺癌标本从2005年至2010年确定的迈阿密大学肿瘤登记处。我们收集了临床数据，包括总生存期（OS），在特定时间间隔存活的患者比例，来自非西班牙裔白色，西班牙裔和黑人患者，按分期匹配。我们进行了免疫组化染色，以检测MMR蛋白在所有标本和聚合酶链反应分析51肿瘤检测MSI.RESULTS：我们检测MMR缺陷28 253例（11.1%），均匀分布在黑人（9.6%），非西班牙裔白人（10.4%），西班牙裔（12.6%）（P= 0.79）。MLH 1和PMS 2的联合缺陷在28例MMR缺陷样本中发现23例（82.1%）; MSH 2和MSH 6在西班牙裔肿瘤样本中最常见（P= 0.03）。51例肿瘤标本中有11例（21.6%）有高水平的MSI，我们观察到MMR和MSI之间的高度一致性（kappa=.81）。肿瘤MMR缺陷患者的OS显著更好（MMR缺陷肿瘤患者与MMR蛋白完整患者的风险比=0.37; 95%置信区间，0.15-0.91; P= 0.03）。种族和民族没有显着的预测OS。结论：MMR缺陷在结直肠肿瘤发生率相似的患者之间的不同种族和民族群体，这是基于253原发性肿瘤标本的免疫组化分析。这一发现表明了在少数人群中通过免疫组化普遍检测结直肠癌的潜在价值，并证实了MMR缺陷对OS的益处。
BACKGROUND & AIMS: Microsatellite instability (MSI) in colorectal cancer cells results from deficient mismatch repair (MMR) protein function, either acquired or from germline alterations such as in patients with Lynch syndrome. Universal screening initiatives for Lynch syndrome have been encouraged. However, little is known about the true prevalence of MMR deficiency and MSI in colorectal tumors among individuals from different racial and ethnic subgroups or their clinical effects in these populations.METHODS: We performed a retrospective analysis of 253 surgically resected, primary colorectal adenocarcinoma specimens identified from the University of Miami tumor registry from 2005 through 2010. We collected clinical data, including overall survival (OS), the proportion of patients alive at specific intervals, from non-Hispanic white, Hispanic, and black patients matched by stage. We performed immunohistochemical staining to detect MMR proteins in all specimens and polymerase chain reaction analysis of 51 tumors to detect MSI.RESULTS: We detected MMR deficiency in 28 of 253 cases (11.1%), evenly distributed among blacks (9.6%), non-Hispanic whites (10.4%), and Hispanics (12.6%) (P=.79). Combined deficiencies in MLH1 and PMS2 were found in 23 of 28 MMR-deficient samples (82.1%); MSH2 and MSH6 were most frequently absent in tumor samples from Hispanics (P=.03). Eleven of 51 tumor samples (21.6%) had high levels of MSI, and we observed a high level of concordance between MMR and MSI (kappa=.81). OS was significantly better in patients whose tumors had deficient MMR (hazard ratio for patients with MMR-deficient tumors vs MMR proteins intact=0.37; 95% confidence interval, 0.15-0.91; P=.03). Race and ethnicity were not significant predictors of OS.CONCLUSIONS: MMR deficiency in colorectal tumors occurs with similar rates among patients of different racial and ethnic groups, which is based on immunohistochemical analysis of 253 primary tumor specimens. This finding indicates the potential value of universal testing of colorectal cancer by immunohistochemistry in minority populations and confirms the benefit of MMR deficiency to OS.