Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
Department of General Surgery, Visceral, Thoracic, Transplantation and Pediatric Surgery, University Hospital Schleswig-Holstein, Kiel, Germany.
Br J Cancer. 2023 Jan;128(2):375-386. doi: 10.1038/s41416-022-02047-3. Epub 2022 Nov 8.
Intratumoral heterogeneity (ITH) is a major problem in gastric cancer (GC). We tested Ki67 and tumor regression for ITH after neoadjuvant/perioperative chemotherapy.
429 paraffin blocks were obtained from 106 neoadjuvantly/perioperatively treated GCs (one to five blocks per case). Serial sections were stained with Masson's trichrome, antibodies directed against cytokeratin and Ki67, and finally digitalized. Tumor regression and three different Ki67 proliferation indices (PI), i.e., maximum PI (KiH), minimum PI (KiL), and the difference between KiH/KiL (KiD) were obtained per block. Statistics were performed in a block-wise (all blocks irrespective of their case-origin) and case-wise manner.
Ki67 and tumor regression showed extensive ITH in our series (maximum ITH within a case: 31% to 85% for KiH; 4.5% to 95.6% for tumor regression). In addition, Ki67 was significantly associated with tumor regression (p < 0.001). Responders (<10% residual tumor, p = 0.016) exhibited prolonged survival. However, there was no significant survival benefit after cut-off values were increased ≥20% residual tumor mass. Ki67 remained without prognostic value.
Digital image analysis in tumor regression evaluation might help overcome inter- and intraobserver variability and validate classification systems. Ki67 may serve as a sensitivity predictor for chemotherapy and an indicator of ITH.
肿瘤内异质性（ITH）是胃癌（GC）的一个主要问题。我们检测了新辅助/围手术期化疗后 Ki67 和肿瘤退缩的 ITH。
从 106 例新辅助/围手术期治疗的 GC 中获得了 429 个石蜡块（每个病例一个至五个块）。用 Masson 三色染色、针对细胞角蛋白和 Ki67 的抗体对连续切片进行染色，最后进行数字化。每个块获得肿瘤退缩和三个不同的 Ki67 增殖指数（PI），即最大 PI（KiH）、最小 PI（KiL）和 KiH/KiL 的差值（KiD）。统计分析采用块内（所有块，不论其病例来源）和病例内方式进行。
在我们的系列中，Ki67 和肿瘤退缩显示出广泛的 ITH（病例内最大 ITH：KiH 为 31%至 85%；肿瘤退缩为 4.5%至 95.6%）。此外，Ki67 与肿瘤退缩显著相关（p<0.001）。应答者（<10%残留肿瘤，p=0.016）的生存时间延长。然而，当残留肿瘤量增加≥20%时，没有显著的生存获益。Ki67 仍然没有预后价值。
肿瘤退缩评估中的数字图像分析可能有助于克服观察者内和观察者间的变异性，并验证分类系统。Ki67 可能作为化疗的敏感性预测指标和 ITH 的指标。
