Enhanced expression of CD74 in gastrointestinal cancers and benign tissues.
Enhanced expression of CD74 in gastrointestinal cancers and benign tissues.
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DOI：
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发表时间：
2011-08
影响因子：
1.4
通讯作者：
D. Gold;R. Stein;J. Burton;D. Goldenberg
中科院分区：
文献类型：
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作者：
D. Gold;R. Stein;J. Burton;D. Goldenberg
CD 74是一种跨膜糖蛋白，与MHC II相关，是一种重要的分子伴侣，调节免疫应答的抗原呈递。此外，CD 74是巨噬细胞迁移抑制因子的受体，当与CD 74结合时，启动存活途径和细胞增殖。福尔马林固定，石蜡包埋的临床标本进行了评估，通过免疫组化程序的CD 74的表达。总体而言，胃肠道癌中的CD 74表达显示出统计学上高于正常组织对应物（P<0.001或更好）。在95%的胰腺癌中观察到CD 74表达，其中大多数病例呈现主要为强烈的弥漫性标记模式。结果表明，在较高级别的癌中有更高表达的趋势（P=0.06）。结直肠癌和胃癌的结果相似，分别为60%和86%，CD 74阳性，呈强烈的弥漫性染色模式。我们假设前体病变表达的CD 74水平与其相应的癌一样高或更高，因为存活途径的激活在肿瘤发展的早期阶段特别重要。对于PanIN病变，在更高级别的PanIN-3病变中有更高的CD 74表达，而结肠腺瘤没有显示出这种趋势，但总体而言，CD 74标记的频率和强度高于结肠癌。这些发现支持了CD 74在胃肠道肿瘤形成和维持中的作用，并为开发能够阻断CD 74功能（特别是在肿瘤细胞内）的治疗药物提供了理论基础。
CD74, a transmembrane glycoprotein that associates with MHC II, is an important chaperone that regulates antigen presentation for immune response. In addition, CD74 is the receptor for macrophage migration-inhibitory factor which, when bound to CD74, initiates survival pathways and cell proliferation. Formalin fixed, paraffin embedded clinical specimens were evaluated by immunohistochemical procedures for expression of CD74. Overall, expression of CD74 within gastrointestinal carcinomas showed a statistically greater expression than in the normal tissue counterparts (P<0.001 or better). CD74 expression was observed in 95% of pancreatic carcinomas with the majority of cases presenting a mostly intense, diffuse labeling pattern. The results suggested a trend towards greater expression within the higher grade carcinomas (P=0.06). Colorectal and gastric carcinomas gave similar results with 60% and 86%, respectively, positive for CD74 with an intense, diffuse staining pattern. We hypothesized that precursor lesions would express levels of CD74 as high, or higher, than their respective carcinomas, since activation of survival pathways would be of particular importance at the early stages of neoplastic development. For PanIN lesions there was greater expression of CD74 within higher grade, PanIN-3 lesions, whereas the colonic adenomas showed no such trend, but overall, a higher frequency and intensity of CD74 labeling than was observed within the colon carcinomas. These findings are supportive of a role for CD74 in the development and maintenance of gastrointestinal neo-plasia, and provide a rationale for development of therapeutic agents that are able to block CD74 function, specifically within the tumor cell.