Clinicopathologic profile, immunophenotype, and genotype of CD274 (PD-L1)-positive colorectal carcinomas.
Clinicopathologic profile, immunophenotype, and genotype of CD274 (PD-L1)-positive colorectal carcinomas.
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DOI：
10.1038/modpathol.2016.185
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发表时间：
2017-03
期刊：
影响因子：
--
通讯作者：
Miettinen M
中科院分区：
文献类型：
--
作者：
Inaguma S;Lasota J;Wang Z;Felisiak-Golabek A;Ikeda H;Miettinen M
CD274 (PD-L1)/PDCD1 (PD-1) 通路对于免疫反应和自我耐受的调节至关重要。异常表达的CD274使肿瘤细胞能够逃避宿主免疫系统，被认为是适应性免疫抵抗的机制。 CD274/PDCD1 免疫检查点的抑制提供了一种有前途的新治疗策略。尽管已在包括结直肠癌在内的不同类型的肿瘤中鉴定出表达CD274的肿瘤细胞，但这些CD274阳性肿瘤的临床病理学特征尚未得到广泛研究。在这项研究中，对 454 例原发性结直肠癌进行了组织学和免疫组织化学分析，以了解 CD274、错配修复 (MMR) 蛋白、肠道分化标记物 (CDX2) 和干细胞标记物（ALCAM、ALDH1A1 和 SALL4）。 CD274 阳性结直肠癌 (54/454 (12%)) 通常 (83%) 涉及右结肠或横结肠，具有低分化和实性/髓质组织学。根据多变量逻辑回归分析，CD274 阳性与低分化组织型（OR：3.32；95% CI：1.46-7.51；P = 0.004）、MMR 缺陷（OR：10.0；95% CI：4.66-21.5；P <0.001）以及由CDX2 和 ALCAM 阳性表达缺失或弱表达（OR：5.51；95% CI：1.66–18.3；P = 0.005）。对任意选定的 66 个结直肠癌的突变分析显示，CD274 阳性肿瘤通常 (88%) 携带 BRAF V600E 突变。因此，由 CD274 阳性定义的结直肠癌显示出与通过锯齿状瘤形成途径产生的肿瘤相关的特征。此外，以缺乏 CDX2 和 ALCAM 显着表达为特征的结直肠癌经常 (71%) 显示 CD274 阳性。这可能表明 CD274 表达与“茎样”表型相关。需要对更大的队列进行进一步评估或实验分析来证实这一观点。
The CD274 (PD-L1)/PDCD1 (PD-1) pathway is crucial for the modulation of immune responses and self-tolerance. Aberrantly expressed CD274 allows tumor cells to evade host immune system and is considered to be a mechanism of adaptive immune resistance. Inhibition of the CD274/PDCD1 immune checkpoint offers a promising new therapeutic strategy. Although CD274-expressing tumor cells have been identified in different types of tumors including colorectal cancer, clinicopathologic profile of these CD274-positive tumors has not been extensively studied. In this study, 454 primary colorectal carcinomas were analyzed histologically and immunohistochemically for CD274, mismatch repair (MMR) proteins, intestinal differentiation marker (CDX2), and stem cell markers (ALCAM, ALDH1A1, and SALL4). CD274-positive colorectal carcinomas (54/454 (12%)) usually (83%) involved the right or transverse colon with poorly differentiated and solid/medullary histology. On the basis of multivariate logistic regression analysis, CD274 positivity was significantly associated with poorly differentiated histotype (OR: 3.32; 95% CI: 1.46–7.51; P = 0.004), MMR deficiency (OR: 10.0; 95% CI: 4.66–21.5; P<0.001), and ‘stem-like’ immunophenotype defined by the loss or weak expression of CDX2 and ALCAM-positivity (OR: 5.51; 95% CI: 1.66–18.3; P = 0.005). Mutation analysis of 66 arbitrary selected colorectal carcinomas revealed that CD274-positive tumors usually (88%) carried the BRAF V600E mutation. Thus, colorectal carcinomas defined by CD274 positivity displayed features associated with tumors arising via the serrated neoplasia pathway. Moreover, colorectal carcinomas characterized by lack of CDX2 and prominent expression of ALCAM frequently (71%) showed CD274 positivity. This might suggest association of CD274 expression with ‘stem-like’ phenotype. Further evaluation of a larger cohort or experimental analyses would be needed to confirm this notion.
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