Departments of Pathology.
USA Health University Hospital, Mobile, AL.
Appl Immunohistochem Mol Morphol. 2021 Sep 1;29(8):557-563. doi: 10.1097/PAI.0000000000000922.
Programmed death-1 (PD1) expression has not been reported in gallbladder adenocarcinoma. In this study we examined PD1 expression in gallbladder cancer to explore the correlation between PD1 expression and the clinicopathologic parameters. We found that 98% (46/47) cases expressed programmed death-ligand 1 (PD-L1) with 85% cases being PD-L1 3+. PD1+ tumor-infiltrating lymphocytes (TILs) were present in 78.7% cases (37/47). The tumor size was significantly smaller and the stromal CD3+ TILs were significantly higher in tumors with PD1+ TILs than those with PD1- TILs. In the tumors with size of <3 cm, stromal CD3+ TILs >115/HPF or stromal CD8+ TILs >45/HPF were associated with much better survival than those with stromal CD3+ TILs ≤115/HPF or stromal CD8+ TILs ≤45/HPF. In tumors with the size of 3 cm or larger, PD1+ TILs or stromal CD8+ TILs >45/HPF carried a significantly poorer survival than PD1- tumors or stromal CD8+ TILs <=45/HPF. No correlation was identified between PD1 expression and lymphovascular invasion, distant metastasis, pathologic tumor stage or prognostic stage. Multivariate survival analysis showed that tumor TNM stage and age were independent prognostic factors in gallbladder adenocarcinomas. We conclude that gallbladder adenocarcinomas may have high PD-L1 expression and PD1+ TILs. Smaller tumor size and greater amount of stromal CD3+ T cells were found in tumors with PD1+ TILs. In small tumors (<3 cm), high stromal CD3+ TILs or high stromal CD8+ TILs were associated with better survival. However, in large tumors (≥3 cm), PD1+ TILs or high stromal CD8+ TILs carried a poorer survival. Our study implied that immune-based therapy including PD1/PD-L1 checkpoint blockade might be useful in gallbladder adenocarcinomas.
程序性死亡受体-1（PD1）在胆囊腺癌中尚未有报道。在本研究中，我们检测了胆囊癌中 PD1 的表达，以探讨 PD1 表达与临床病理参数之间的关系。我们发现 98%（46/47）的病例表达程序性死亡配体 1（PD-L1），其中 85%为 PD-L13+。78.7%（47/47）的病例存在 PD1+肿瘤浸润淋巴细胞（TILs）。与 PD1-TILs 相比，PD1+TILs 的肿瘤直径更小，基质中 CD3+TILs 更高。在直径<3cm 的肿瘤中，基质中 CD3+TILs>115/HPF 或基质中 CD8+TILs>45/HPF 与生存时间显著延长相关，而基质中 CD3+TILs≤115/HPF 或基质中 CD8+TILs≤45/HPF 则与之相反。在直径为 3cm 或更大的肿瘤中，PD1+TILs 或基质中 CD8+TILs>45/HPF 的患者比 PD1-TILs 或基质中 CD8+TILs≤45/HPF 的患者预后更差。PD1 表达与淋巴血管侵犯、远处转移、病理肿瘤分期或预后分期之间均无相关性。多因素生存分析显示，肿瘤 TNM 分期和年龄是胆囊腺癌的独立预后因素。我们的研究结果表明，胆囊腺癌可能存在高 PD-L1 表达和 PD1+TILs。在 PD1+TILs 的肿瘤中，肿瘤直径较小，基质中 CD3+T 细胞数量较多。在小肿瘤（<3cm）中，基质中 CD3+TILs 或基质中 CD8+TILs 较高与生存时间延长相关。然而，在大肿瘤（≥3cm）中，PD1+TILs 或基质中 CD8+TILs 则与生存时间缩短相关。我们的研究表明，包括 PD1/PD-L1 检查点阻断在内的免疫治疗可能对胆囊腺癌有效。
