Kim Jung Ho, Rhee Ye-Young, Kim Kyung-Ju, Cho Nam-Yun, Lee Hye Seung, Kang Gyeong Hoon
Department of Pathology, SMG-SNU Boramae Medical Center, Seoul, South Korea.
APMIS. 2014 Dec;122(12):1187-95. doi: 10.1111/apm.12284. Epub 2014 Jun 7.
Annexin A10 (ANXA10) has recently been identified as a marker of sessile serrated adenomas/polyps of the colorectum. Although the serrated neoplasia pathway is thought to be involved in the majority of microsatellite instability-high (MSI-H) sporadic colorectal carcinomas (CRCs), the clinicopathological implications of ANXA10 expression in CRC are unknown. Here, we evaluated ANXA10 expression status in 168 MSI-H CRCs by immunohistochemistry. Among 168 MSI-H CRCs, nuclear staining for ANXA10 in tumor cells revealed 28 cases (17%) with ANXA10-positive (ANXA10+) tumors. Most of the ANXA10+ tumors were located in the proximal colon (96%, p < 0.001). The ANXA10+ phenotype in MSI-H CRC was significantly associated with female gender (68%, p = 0.016), CpG island methylator phenotype-high (CIMP-H) (68%, p < 0.001), MLH1 promoter hypermethylation (61%, p < 0.001), loss of MLH1 expression (82%, p = 0.019), and wild-type KRAS status (96%, p = 0.023). Survival analysis revealed no prognostic significance of ANXA10 expression in MSI-H CRC. In conclusion, ANXA10+ MSI-H colon carcinomas are characterized by serrated pathway features, including proximal location, female predominance, and high frequencies of CIMP-H status and MLH1 methylation.
膜联蛋白A10（ANXA10）最近被确定为结直肠无蒂锯齿状腺瘤/息肉的标志物。尽管锯齿状肿瘤发生途径被认为参与了大多数微卫星高度不稳定（MSI-H）散发性结直肠癌（CRC），但ANXA10在CRC中的临床病理意义尚不清楚。在此，我们通过免疫组织化学评估了168例MSI-H CRC中ANXA10的表达状态。在168例MSI-H CRC中，肿瘤细胞中ANXA10的核染色显示28例（17%）为ANXA10阳性（ANXA10+）肿瘤。大多数ANXA10+肿瘤位于近端结肠（96%，p<0.001）。MSI-H CRC中的ANXA10+表型与女性性别（68%，p=0.016）、CpG岛甲基化表型高（CIMP-H）（68%，p<0.001）、MLH1启动子高甲基化（61%，p<0.001）、MLH1表达缺失（82%，p=0.019）和KRAS野生型状态（96%，p=0.023）显著相关。生存分析显示ANXA10表达在MSI-H CRC中无预后意义。总之，ANXA10+ MSI-H结肠癌具有锯齿状途径特征，包括近端位置、女性占优势以及CIMP-H状态和MLH1甲基化的高频率。
