Sacdalan Dennis Lee, Garcia Reynaldo L, Diwa Michele H, Sacdalan Danielle Benedict
Division of Medical Oncology, Department of Medicine, University of the Philippines, Manila, Philippines.
National Institute of Molecular Biology and Biotechnology, University of the Philippines, Diliman, Quezon City, Philippines.
Cancer Manag Res. 2021 Mar 1;13:2105-2115. doi: 10.2147/CMAR.S286618. eCollection 2021.
Young-onset colorectal cancer is recognized as a distinct disease that may be sporadic or hereditary in nature. Microsatellite instability testing is recommended as a routine procedure in evaluating colorectal cancer specimens, especially in young-onset disease, because of implications in management. Immunohistochemistry of mismatch repair proteins serves as an inexpensive alternative to microsatellite instability testing with the added advantage of monitoring protein expression levels that may suggest underlying genetic or epigenetic alterations. This descriptive study aimed to determine the frequencies of proficient and deficient mismatch repair status among Filipino young-onset colorectal cancer patients, and to investigate their clinicopathologic profile.
Tumor tissues were prospectively collected from patients from two tertiary hospitals in the Philippines. Patients of age ≤45 years with resected adenocarcinoma of the colon or rectum were recruited.
Seventy-seven out of 124 patients had tumor samples sent for immunohistochemistry. Of these, 61 samples (79%) were found to have proficient status while 16 samples (21%) had deficient status. Mismatch repair protein deficiencies, when present, more commonly involved MSH2 and MSH6 (9%) rather than MLH1 and PMS2 (5%). The deficient group had a mean age of 37.1 years and a female preponderance (56.25%), presenting as locally advanced ascending or descending colon tumors with mucinous histology in half of the population. The mismatch repair proficient group presented as locally advanced rectal and sigmoid tumors but with fewer mucinous adenocarcinomas (26.2%) compared to the deficient group. In both the mismatch repair proficient and deficient patients with family history reports, most did not have any known relative with cancer (75.4% and 68.75%, respectively).
This is the first attempt to perform mismatch repair testing among young-onset colorectal cancer patients in the Philippines and to gather data on their clinicopathologic characteristics. However, the limited sample size precludes conclusive results for the associations of mismatch repair with clinicopathologic features.
青年期结直肠癌被认为是一种独特的疾病，其本质可能是散发性的或遗传性的。由于对治疗的影响，微卫星不稳定性检测被推荐作为评估结直肠癌标本的常规程序，尤其是在青年期疾病中。错配修复蛋白的免疫组化是微卫星不稳定性检测的一种廉价替代方法，其额外优势在于可监测可能提示潜在基因或表观遗传改变的蛋白表达水平。本描述性研究旨在确定菲律宾青年期结直肠癌患者中错配修复状态熟练和缺陷的频率，并调查其临床病理特征。
前瞻性收集来自菲律宾两家三级医院患者的肿瘤组织。招募年龄≤45岁、患有结肠或直肠腺癌且已切除的患者。
124例患者中有77例将肿瘤样本送检免疫组化。其中，61份样本（79%）错配修复状态熟练，16份样本（21%）错配修复状态缺陷。错配修复蛋白缺陷若存在，更常见于MSH2和MSH6（9%），而非MLH1和PMS2（5%）。缺陷组的平均年龄为37.1岁，女性占优势（56.25%），一半患者表现为局部进展期升结肠或降结肠肿瘤，组织学类型为黏液性。错配修复熟练组表现为局部进展期直肠和乙状结肠肿瘤，但黏液腺癌的比例（26.2%）低于缺陷组。在有家族史报告的错配修复熟练和缺陷患者中，大多数没有已知的癌症亲属（分别为75.4%和68.75%）。
这是菲律宾首次对青年期结直肠癌患者进行错配修复检测，并收集其临床病理特征数据。然而，样本量有限，无法得出错配修复与临床病理特征相关性的确切结果。
