Ichimura Takashi, Abe Hiroyuki, Morikawa Teppei, Yamashita Hiroharu, Ishikawa Shumpei, Ushiku Tetsuo, Seto Yasuyuki, Fukayama Masashi
Department of Chemotherapy, Gastroenterology Center, Gastroenterological Internal Medicine, the Cancer Institute Hospital of JFCR (Japanese Foundation for Cancer Research), Tokyo 135-8550, Japan; Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Hum Pathol. 2016 Oct;56:74-80. doi: 10.1016/j.humpath.2016.06.002. Epub 2016 Jun 21.
Recent studies suggest that CD204-positive (CD204(+)) M2-type tumor-associated macrophages (TAMs) are associated with the aggressive behavior of various cancers. However, the clinicopathologic significance of tumor-infiltrating CD204(+) macrophages and their correlation with Epstein-Barr virus (EBV) in gastric cancer is unclear. Tissue microarrays were constructed from 119 surgically resected gastric cancer specimens (86 EBV-negative and 28 EBV-positive cases). After immunohistochemistry of CD204, the density of CD204(+) cells was calculated using image analysis software, and associations between CD204 and clinicopathologic factors including patient survival were examined. High CD204(+) cell density was significantly associated with several adverse prognostic factors, including older age (P = .008), advanced tumor depth (P < .001), lymph node metastasis (P < .001), presence of venous invasion (P < .001), and lymphatic invasion (P = .03). Low CD204(+) cell density was significantly associated with EBV infection. Advanced tumor depth and presence of lymph node metastasis were significantly associated with high CD204(+) cell density in both EBV-positive and EBV-negative subgroups. High CD204(+) cell density was significantly associated with shorter cancer-specific survival (P = .0015). In conclusion, a high density of CD204(+) TAMs was associated with the aggressive behavior and worse survival of gastric cancer. Low density of CD204(+) TAMs was associated with infection of EBV, which may explain the favorable outcome of EBV-associated gastric carcinoma. Our results suggest that a specific immune microenvironment may be associated with the biological behavior of gastric cancer and that EBV-associated gastric carcinoma is distinctive from other gastric carcinomas in tumor immunity.
近期研究表明，CD204阳性（CD204(+)）的M2型肿瘤相关巨噬细胞（TAM）与多种癌症的侵袭性行为相关。然而，胃癌中肿瘤浸润性CD204(+)巨噬细胞的临床病理意义及其与爱泼斯坦-巴尔病毒（EBV）的相关性尚不清楚。从119例手术切除的胃癌标本（86例EBV阴性和28例EBV阳性病例）构建组织芯片。对CD204进行免疫组织化学染色后，使用图像分析软件计算CD204(+)细胞的密度，并检测CD204与包括患者生存在内的临床病理因素之间的关联。高CD204(+)细胞密度与几个不良预后因素显著相关，包括年龄较大（P = .008）、肿瘤深度进展（P < .001）、淋巴结转移（P < .001）、静脉侵犯（P < .001）和淋巴管侵犯（P = .03）。低CD204(+)细胞密度与EBV感染显著相关。在EBV阳性和EBV阴性亚组中，肿瘤深度进展和淋巴结转移的存在均与高CD204(+)细胞密度显著相关。高CD204(+)细胞密度与较短的癌症特异性生存期显著相关（P = .0015）。总之，高密度的CD204(+) TAM与胃癌的侵袭性行为和较差的生存率相关。低CD204(+) TAM密度与EBV感染相关，这可能解释了EBV相关胃癌的良好预后。我们的结果表明，特定的免疫微环境可能与胃癌的生物学行为相关，并且EBV相关胃癌在肿瘤免疫方面与其他胃癌不同。
