Department of Pathology, Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil; Department of Gastroenterology, Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
Department of Pathology, Instituto do Cancer do Estado de São Paulo, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
J Surg Res. 2021 May;261:130-138. doi: 10.1016/j.jss.2020.12.029. Epub 2021 Jan 8.
Epstein-Barr virus (EBV) positive gastric cancer (GC) has been described as a distinct molecular subtype of the disease, especially associated with gastric carcinoma with lymphoid stroma (GCLS). The possibility that EBV associated GC (EBVaGC) had better prognosis and may be susceptible to immunotherapy has increased the interest in this subtype. However, immune checkpoint and survival of EBVaGC are still controversial, especially with regard to GCLS and conventional gastric adenocarcinoma (CGA). This study aimed to evaluate the clinicopathological characteristics, immunohistochemical profiles and prognosis of EBVaGC according to the histological type GCLS and CGA.
we retrospectively evaluated a series of EBVaGC who underwent gastrectomy with D2-lymphadenectomy. Biomarkers and tumor-infiltrating cells were evaluated by immunohistochemistry. PD-L1 was evaluated using a combined positive score (CPS).
From a total of 30 EBVaGC, 14 (46.7%) were identified as GCLS and 16 (53.3%) as CGA (9 Intestinal, 6 diffuse, 1 undetermined). There were no significant differences in age, sex, and pTNM between GCLS and CGA. CPS-positivity and high-CD8 was significantly higher in GCLS compared with CGA (P = 0.007 and P = 0.005, respectively). Diffuse EBVaGC had worse survival than intestinal type (P = 0.020). There was no difference in survival between GCLS and intestinal CGA (P = 0.260). In multivariate analysis, CPS and pN status were related with survival in EBVaGC.
CGLS was associated with a predominance of CD8 cell infiltration and PD-L1 expression. CPS and lymph node metastasis were independent factors associated with prognosis in EBVaGC. These results suggest that specifically EBV-positive GCLS may be prime candidates for PD-1 directed therapy.
已发现 EBV 阳性胃癌（GC）是一种独特的疾病分子亚型，尤其是与淋巴上皮样癌（GCLS）相关的胃腺癌。由于 EBV 相关 GC（EBVaGC）具有更好的预后且可能对免疫治疗敏感，因此人们对这种亚型的兴趣有所增加。然而，EBVaGC 的免疫检查点和生存情况仍存在争议，尤其是对于 GCLS 和传统胃腺癌（CGA）。本研究旨在根据组织学类型 GCLS 和 CGA 评估 EBVaGC 的临床病理特征、免疫组化特征和预后。
我们回顾性评估了接受 D2 淋巴结清扫术的 EBVaGC 患者系列。通过免疫组化评估生物标志物和肿瘤浸润细胞。使用组合阳性评分（CPS）评估 PD-L1。
在总共 30 例 EBVaGC 中，14 例（46.7%）被确定为 GCLS，16 例（53.3%）为 CGA（9 例为肠型，6 例为弥漫型，1 例未确定）。GCLS 和 CGA 之间在年龄、性别和 pTNM 方面没有显著差异。GCLS 中 CPS 阳性和高 CD8 的比例明显高于 CGA（P=0.007 和 P=0.005）。弥漫型 EBVaGC 的生存情况较肠型差（P=0.020）。GCLS 和肠型 CGA 之间的生存情况无差异（P=0.260）。在多变量分析中，CPS 和 pN 状态与 EBVaGC 的生存相关。
GCLS 与 CD8 细胞浸润和 PD-L1 表达为主有关。CPS 和淋巴结转移是 EBVaGC 预后的独立因素。这些结果表明，特定的 EBV 阳性 GCLS 可能是 PD-1 导向治疗的首选候选者。
