In Epstein-Barr virus-associated gastric carcinoma a high density of CD66b-positive tumor-associated neutrophils is associated with intestinal-type histology and low frequency of lymph node metastasis
In Epstein-Barr virus-associated gastric carcinoma a high density of CD66b-positive tumor-associated neutrophils is associated with intestinal-type histology and low frequency of lymph node metastasis
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DOI：
10.1007/s00428-016-1915-z
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发表时间：
2016-05-01
期刊：
影响因子：
3.5
通讯作者：
Fukayama, Masashi
中科院分区：
文献类型：
--
作者：
Abe, Hiroyuki;Morikawa, Teppei;Fukayama, Masashi
EB病毒相关胃癌（EBVaGC）的特征是显著的肿瘤内淋巴细胞浸润，伴有其他类型的炎性细胞（如中性粒细胞）浸润。在这项研究中，肿瘤相关的中性粒细胞（TANs）和细胞毒性T淋巴细胞（CTLs）的EBVaGC的意义进行了研究。通过免疫组织化学和数字成像分析来评估手术切除的EBVaGC组织中的CD 66 b阳性TAN和CD 8阳性CTL。用受试者工作特征曲线分析确定临界值。77例中有42例（55%）有一定程度的TAN浸润（CD 66 b阳性区域> 0.5%，TAN（+）），35例（45%）有少量浸润（TAN（-））。35例（45%）具有更多的CTL（CD 8阳性面积> 18%，CTL高），42例（55%）具有较少的CTL（CTL低）。肿瘤中CD 66 b和CD 8阳性面积之间无相关性（P = 0.453）。TAN（+）与肿瘤组织学类型（P = 0.048）和低淋巴结转移率（P = 0.023）相关，而CTL-低与肿瘤位置（P = 0.030）和浸润深度（pT 2或更深）（P = 0.006）相关。疾病特异性生存率与TAN或CTL无显著相关性。多因素Logistic回归分析显示TAN（-）与淋巴结转移独立相关（P = 0.036）。TAN（+）早期EBVaGC伴粘膜下浸润的病例均未显示淋巴结转移（95%置信区间0- 13.3%）。与24例EBV阴性胃癌相比，EBVaGC中CTLs的表达明显增多（P < 0.001），而TANs的表达无明显差异。在EBVaGC中的TAN可能抑制淋巴结转移，并且在内窥镜切除术后的病例中没有TAN可能建议仔细随访或额外治疗。
Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is characterized by prominent intratumoral lymphocyte infiltration, with some infiltration by other types of inflammatory cells, such as neutrophils. In this study, the significance of tumor-associated neutrophils (TANs) and cytotoxic T lymphocytes (CTLs) was investigated in EBVaGC. CD66b-positive TANs and CD8-positive CTLs in surgically resected EBVaGC tissues were evaluated by immunohistochemistry and digital imaging analysis. Cut-off values were determined with receiver operating characteristic curve analyses. Forty-two of 77 cases (55 %) had some infiltration of TANs (CD66b-positive areas >0.5 %, TAN(+)) and 35 (45 %) had scant infiltration (TAN(-)). Thirty-five cases (45 %) had more CTLs (CD8-positive area >18 %, CTL-high) and 42 (55 %) had fewer (CTL-low). There was no correlation between CD66b- and CD8-positive areas in the tumor (P = 0.453). TAN(+) correlated with intestinal-type histology (P = 0.048) and low frequency of lymph node metastasis (P = 0.023), while CTL-low with upper location (P = 0.030) and advanced invasion depth (pT2 or greater) (P = 0.006). Disease-specific survival was not significantly correlated with TANs or CTLs. Multivariate logistic regression analysis revealed TAN(-) to be independently associated with lymph node metastasis (P = 0.036). None of the cases of TAN(+) early EBVaGC with submucosal invasion showed lymph node metastasis (95 % confidence interval 0-13.3 %). When compared with 24 EBV-negative gastric carcinomas, EBVaGC had significantly more CTLs (P < 0.001), while there was no difference in the number of TANs. TANs in EBVaGC may suppress lymph node metastasis, and absence of TANs might suggest careful follow-up or additional therapy in cases of post-endoscopic resection.