Master of Science in Clinical Research Program, University of Puerto Rico, San Juan, PR, USA.
Fam Cancer. 2010 Jun;9(2):155-66. doi: 10.1007/s10689-009-9310-4.
Colorectal cancer (CRC) is a leading cause of morbidity and mortality and alterations in mismatch repair (MMR) genes, leading to absent protein (negative) expression, are responsible for approximately 20% of CRC cases. Immunohistochemistry is a tool for prescreening of MMR protein expression in CRC but the literature on its use on Hispanics is scarce. However, Hispanics represent the second leading ethnicity in the United States (US) and CRC is a public health burden in this group. Our objectives were to determine the frequency of MMR protein-negative CRC and to evaluate its association with clinical and pathological characteristics among Hispanics from Puerto Rico, for the first time to our knowledge. A retrospective observational study of unselected CRC patients from the Puerto Rico Medical Center from 2001 to 2005 was done. MLH1 and MSH2, the most commonly altered MMR genes, protein expression was evaluated using immunohistochemistry, with microsatellite instability (MSI) and BRAF gene analyses in the absence of MLH1 protein expression. One-hundred sixty-four CRC patients were evaluated: the overall MMR protein-negative frequency was 4.3%, with 0.6% frequency of co-occurrence of MLH1-protein negative expression, MSI-high, and normal BRAF gene. MMR protein-negative expression was associated with proximal colon location (P = 0.02) and poor histological tumor differentiation (P = 0.001), but not with other characteristics. The frequency of MMR protein-negative CRC in Hispanics from Puerto Rico was lower than reported in other populations. This finding may explain the lower CRC incidence rate among US Hispanics as compared to US non-Hispanic whites and blacks.
结直肠癌(CRC)是发病率和死亡率的主要原因,错配修复(MMR)基因的改变导致蛋白缺失(阴性)表达,约占 CRC 病例的 20%。免疫组织化学是 CRC 中 MMR 蛋白表达的预筛选工具,但关于其在西班牙裔人群中的应用的文献很少。然而,西班牙裔是美国第二大主要种族,CRC 是该人群的公共卫生负担。我们的目标是确定 MMR 蛋白阴性 CRC 的频率,并首次评估其与波多黎各西班牙裔 CRC 患者的临床和病理特征的相关性。对 2001 年至 2005 年波多黎各医疗中心未经选择的 CRC 患者进行了回顾性观察性研究。使用免疫组织化学评估最常改变的 MMR 基因 MLH1 和 MSH2 的蛋白表达,在 MLH1 蛋白表达缺失的情况下进行微卫星不稳定性(MSI)和 BRAF 基因分析。评估了 164 例 CRC 患者:总体 MMR 蛋白阴性频率为 4.3%,MLH1 蛋白阴性表达、MSI 高和正常 BRAF 基因共发生频率为 0.6%。MMR 蛋白阴性表达与结肠近端位置(P=0.02)和组织学肿瘤分化不良(P=0.001)相关,但与其他特征无关。波多黎各西班牙裔的 MMR 蛋白阴性 CRC 频率低于其他人群。这一发现可能解释了与美国非西班牙裔白人和黑人相比,美国西班牙裔 CRC 发病率较低的原因。