胃癌中PD-L1蛋白表达及分布特征的病理学意义

目的检测胃癌中程序性死亡配体-1(programmed death ligand-1,PD-L1)蛋白的表达,总结其在癌组织及癌间质中肿瘤浸润单核细胞(tumor infiltrating mononuclear cells,TIMCs)中的表达水平及分布特征,探讨影响胃癌PD-L1蛋白表达的病理学因素,以提高其判读的准确性及可重复性。方法收集安徽医科大学第四附属医院2015~2019年期间110例行胃癌根治切除术标本,运用免疫组化MaxVision两步法检测PD-L1蛋白表达,观察其在癌组织及TIMCs中的表达水平及分布特征,计算并比较不同判读方法下PD-L1蛋白表达及其检测阳性率的差异,并分析其与临床病理学特征及临床预后的关系。结果运用CPS、TPS及MIDS三种不同的判读方法,胃癌中PD-L1蛋白的检测阳性率分别为46.4%、24.5%、42.7%,三者一致性较好(P<0.05)。其中运用CPS检测的阳性率最高,且呈高表达者最多。CPS、TPS及MIDS三者检测阳性率与胃癌肿瘤实质性坏死、TIMCs数量、肿块大小呈正相关(P<0.05),其中CPS检测PD-L1表达还与癌组织浸润深度相关(P<0.05),但与患者性别、年龄、肿瘤病变部位、组织学类型等均无关。PD-L1蛋白高表达者在胃癌组织的分布以弥漫性分布特征为主,低表达者以斑驳样分布特征为主,且无论表达高低均存在癌巢与间质接触面区域PD-L1着色强度较高的苔藓样分布特征。TIMCs中PD-L1阳性表达亦以苔藓样分布特征为主,着色细胞主要是淋巴细胞、巨噬细胞等,且接触面并列分布的癌细胞也更易见PD-L1阳性表达。结论胃癌中PD-L1蛋白检测以CPS判读指标为优。进展期胃癌中,当肿块直径>5.0 cm、TIMCs数目较多、肿瘤实质性坏死明显时,PD-L1均易呈阳性,且癌巢与间质接触面区域易出现PD-L1表达或表达较高的情况,判读时要注意观察。

Pathological study on expression and distribution of PD-L1 protein in gastric cancer

Purpose To detect the expression of programmed death ligand-1 (PD-L1) protein in gastric cancer, and to summarize the expression level and distribution characteristics of PD-L1 in the cancer cells and the tumor infiltrating mononuclear cells (TIMCs) of cancer stroma. To explore the pathological factors affecting the expression of PD-L1 protein in gastric cancer in order to improve the accuracy and repeatability of its interpretation. Methods 110 cases of gastric cancer undergoing radical gastrectomy in our hospital from 2015 to 2019 were collected. The expression of PD-L1 protein was detected by immunohistochemical method, whose expression level and distribution characteristics in cancer tissues and TIMCs were observed. The expression of PD-L1 protein and the positive rate of PD-L1 detection under different interpretation methods were calculated and compared, statistical methods were used to analyze the relationship between pathological features and clinical prognosis. Results The positive rates of PD-L1 protein in gastric cancer were 46.4%, 24.5% and 42.7% respectively by CPS, TPS and MIDS, and the consistency of the three methods was good ( P <0.05). The highest positive rate was detected by CPS, and the highest expression was found. The positive rates of CPS, TPS and MIDS in gastric cancer were positively correlated with tumor necrosis, the number of TIMCs and the size of tumors ( P <0.05). CPS was also correlated with the depth of invasion of cancer tissue ( P <0.05), but not with gender, age, location and histological type of tumors. The distribution of high PD-L1 expression was diffuse in gastric cancer tissues, while the low expression of PD-L1 was mottled in gastric cancer tissues. The distribution of PD-L1 protein was lichenoid pattern in the interface area between cancer nest and stroma, regardless of the level of PD-L1 protein expression. In TIMCs, the expression of PD-L1 was lichenoid pattern, and the main staining cells were lymphocytes and macrophages. It was more easily to see the positive expression of PD-L1 in cancer cells distributed side by side on the contact surface. Conclusion CPS is the best index for detecting PD-L1 protein in gastric cancer. In advanced gastric cancer, when the size of the mass is larger than 5 cm, the number of TIMCs is larger, and the substantial necrosis of the tumor is obvious, the expression of PD-L1 prefer to be positive. The expression of PD-L1 in the contact area between the cancer nest and stroma prefer to high, so we should pay attention to observe it.