Wang Lili, Liu Qin, Lin Dongliang, Lai Maode
Department of Pathology, School of Medicine, Zhejiang UniversityHangzhou 310058, Zhejiang, China; Key Laboratory of Disease Proteomics of Zhejiang Province Hangzhou 310058Zhejiang, China.
Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao University Qingdao, China.
Int J Clin Exp Pathol. 2015 Nov 1;8(11):14283-93. eCollection 2015.
We aim to investigate the variation of CD44v6 expression in the normal-adenoma-primary carcinoma-liver metastasis sequence and its prognostic impact on colorectal carcinomas. The difference in CD44v6 expression between the tumor center and invasive front was also assessed. Immunohistochemistry was performed for CD44v6 on two cohorts. The first was tissue microarrays including 402 primary CRCs sampled from the tumor center and the invasive margin. The second was whole-tissue sections, consisting of 217 adenomas, 72 primary carcinomas, and the corresponding metastatic carcinomas. In the first cohort, we found that CD44v6 down-regulation was inclined to lymph node metastasis and perineural invasion, and had an unfavorable prognosis compared with CD44v6 up-regulation. In the second cohort, CD44v6 expression was predominant in adenoma over primary carcinoma and liver metastasis in multiple steps (normal < adenoma > primary carcinoma and liver metastasis). In addition, our analysis showed that CD44v6 expression was decreased at the invasion front of the CRC compared with the center of the tumor. In conclusion, the maximal expression of CD44v6 in adenoma plays a crucial role in colorectal carcinogenesis, while loss of CD44v6 expression on the cell surface of the tumor edge enhances the progression of metastasis. CD44v6 down-regulation is an independent prognostic factor for strikingly worse disease-specific survival.
我们旨在研究CD44v6在正常组织-腺瘤-原发性癌-肝转移序列中的表达变化及其对结直肠癌的预后影响。同时也评估了肿瘤中心与浸润前沿CD44v6表达的差异。对两个队列进行了CD44v6免疫组化检测。第一个队列是组织芯片，包括从肿瘤中心和浸润边缘采集的402例原发性结直肠癌。第二个队列是全组织切片，由217例腺瘤、72例原发性癌及相应的转移癌组成。在第一个队列中，我们发现CD44v6下调倾向于发生淋巴结转移和神经周围浸润，与CD44v6上调相比预后不良。在第二个队列中，CD44v6表达在腺瘤中占主导，在原发性癌和肝转移中呈多步骤递减（正常＜腺瘤＞原发性癌和肝转移）。此外，我们的分析表明，与肿瘤中心相比，结直肠癌浸润前沿的CD44v6表达降低。总之，CD44v6在腺瘤中的最大表达在结直肠癌发生中起关键作用，而肿瘤边缘细胞表面CD44v6表达缺失会促进转移进展。CD44v6下调是疾病特异性生存率显著降低的独立预后因素。
