Institute of Pathology, University Hospital Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, Cologne, Germany.
Gastric Cancer. 2021 Sep;24(5):1115-1122. doi: 10.1007/s10120-021-01195-4. Epub 2021 May 5.
PD-1/PD-L1-Immunotherapy has been approved for gastric carcinoma. PD-L1 assessment by immunohistochemistry is the principle biomarker. Are biopsies able to map the actual PD-L1 status of the entire tumor?
Whole tumor slides of 56 gastric carcinoma were analyzed to determine the distribution of PD-L1 positive cells in the entire tumor areas. Tissue micro arrays with four cores of the tumor surface, which represents the endoscopically accessible biopsy zone, were built from the same tumors. The PD-L1 CPS value was determined separately for each core. Preoperative diagnostic biopsies were available for 22 of the tumors. PD-L1 prevalence, sensitivity and specificity were analyzed using the whole tumor slides as reference scores. Molecular subtyping was performed and related to the PD-L1 status.
27.3% of cases were PD-L1 negative (CPS < 1), 43.6% showed low PD-L1 expression (CPS ≥ 1 to < 5), 12.7% moderate (CPS ≥ 5 to < 10) and 16.4% strong expression (CPS ≥ 10). The biopsies showed best test characteristics if four surface biopsies were analyzed combined, i.e., the CPS was calculated across all four biopsies. The prevalence showed a distribution similar to the resection specimens, sensitivity was 0.73 and specificity 1.0. Using fewer surface biopsies decreased sensitivity and specificity and caused false-negative classifications. Compared to the TMAs, the preoperative biopsies showed reduced sensitivity (0.412).
This is the first comprehensive study to optimize PD-L1 assessment in gastric cancer using endoscopically available tissue. The obtained PD-L1 prevalence is consistent with data of current clinical studies. Calculation of the test characteristics shows that surface biopsies can be indicative of the true PD-L1 status based on the resection specimen. However, an adequate number of biopsies is required. In this study, n = 4 biopsies yielded best results.
PD-1/PD-L1 免疫疗法已被批准用于胃癌。免疫组织化学 PD-L1 评估是主要的生物标志物。活检能否描绘整个肿瘤的实际 PD-L1 状态？
分析了 56 例胃癌的全肿瘤切片，以确定整个肿瘤区域中 PD-L1 阳性细胞的分布。从同一肿瘤构建了具有肿瘤表面四个核心的组织微阵列，这代表了可内镜活检的区域。分别确定了每个核心的 PD-L1 CPS 值。22 例肿瘤中有术前诊断性活检。使用全肿瘤切片作为参考评分，分析 PD-L1 患病率、敏感性和特异性。进行了分子分型，并与 PD-L1 状态相关。
27.3%的病例为 PD-L1 阴性（CPS<1），43.6%表现为低 PD-L1 表达（CPS≥1 至<5），12.7%为中度（CPS≥5 至<10），16.4%为强表达（CPS≥10）。如果分析 4 个表面活检的组合，则活检显示最佳的测试特征，即通过所有 4 个活检计算 CPS。患病率的分布与切除标本相似，敏感性为 0.73，特异性为 1.0。使用较少的表面活检会降低敏感性和特异性，并导致假阴性分类。与 TMAs 相比，术前活检的敏感性降低（0.412）。
这是第一项使用可内镜获得的组织优化胃癌 PD-L1 评估的综合研究。获得的 PD-L1 患病率与当前临床研究的数据一致。测试特征的计算表明，基于切除标本，表面活检可以指示真实的 PD-L1 状态。但是，需要足够数量的活检。在这项研究中，n=4 个活检获得了最佳结果。
Zotero 插件