Department of Surgery, Nara Medical University, Kashihara-Shi, Nara, Japan.
Ann Surg Oncol. 2019 Nov;26(12):3982-3989. doi: 10.1245/s10434-019-07625-z. Epub 2019 Jul 16.
Herpesvirus entry mediator (HVEM) has been suggested to play various roles in cancer biology. The authors report that HVEM expression in tumor cells is associated with a reduction in the number of tumor-infiltrating lymphocytes and a poor prognosis after surgical resection in various human gastrointestinal cancers. This study aimed to clarify the clinical significance of HVEM expression in human colorectal liver metastasis (CRLM).
This study examined the cases of 104 patients with CRLM who underwent curative liver resection at Nara Medical University between 2000 and 2014. The median follow-up period was 50.2 months. Immunohistochemical staining was performed using antibodies against HVEM, CD4, CD8, and CD45RO.
High HVEM expression was observed in 49 patients (47.1%) with CRLM. Expression of HVEM was not associated with age, gender, administration of preoperative chemotherapy, tumor size, number of tumors, or histologic differentiation. The high-HVEM group exhibited significantly worse overall survival (OS) than the low-HVEM group (P = 0.002). Multivariate analysis showed that high HVEM expression in CRLM, age of 70 years or older, and having five or more tumors are independent poor prognostic factors for OS (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.41-7.93; P = 0.006). The number of tumor-infiltrating CD8+ and CD45RO+ T cells was significantly lower in the high-HVEM group than in the low-HVEM group. High HVEM expression in primary colorectal cancer was significantly associated with synchronous CRLM, but not with metachronous CRLM.
Tumor HVEM expression might play a critical role in CRLM.
疱疹病毒进入介体（HVEM）在癌症生物学中被认为具有多种作用。作者报告称，在各种人类胃肠道癌中，肿瘤细胞中 HVEM 的表达与肿瘤浸润淋巴细胞数量减少以及手术切除后的不良预后相关。本研究旨在阐明 HVEM 在人结直肠癌肝转移（CRLM）中的表达的临床意义。
本研究检查了 2000 年至 2014 年期间在奈良医科大学接受根治性肝切除术的 104 例 CRLM 患者的病例。中位随访时间为 50.2 个月。使用针对 HVEM、CD4、CD8 和 CD45RO 的抗体进行免疫组织化学染色。
在 104 例 CRLM 患者中，有 49 例（47.1%）观察到 HVEM 高表达。HVEM 的表达与年龄、性别、术前化疗的使用、肿瘤大小、肿瘤数量或组织学分化无关。高-HVEM 组的总生存期（OS）明显劣于低-HVEM 组（P=0.002）。多变量分析显示，CRLM 中 HVEM 高表达、年龄 70 岁或以上以及有 5 个或更多肿瘤是 OS 的独立不良预后因素（风险比 [HR]，3.35；95%置信区间 [CI]，1.41-7.93；P=0.006）。高-HVEM 组肿瘤浸润的 CD8+和 CD45RO+T 细胞数量明显低于低-HVEM 组。原发性结直肠癌中 HVEM 的高表达与同步 CRLM 显著相关，但与异时性 CRLM 无关。
肿瘤 HVEM 的表达可能在 CRLM 中发挥关键作用。
