Department of Pathology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
Department of Gastrointestinal Surgery, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo, 113-0033, Japan.
Gastric Cancer. 2024 Jul;27(4):802-810. doi: 10.1007/s10120-024-01505-6. Epub 2024 May 9.
Gastric cancer with peritoneal dissemination (PD) has a dismal prognosis, and current treatments have shown little efficacy. CLDN18.2-targeted therapies have shown promising efficacy against gastric cancers that express high levels of CLDN18. Because of the limited information regarding CLDN18.2 status in PD, we analyzed PD-positive gastric cancers for CLDN18 status in both primary and PD, along with HER2 and PD-L1 combined positive score (CPS).
Immunohistochemical analyses were performed on 84 gastric cancer cases using paired primary and PD tissue samples.
At 40% cut-off, CLDN18 was positive in 57% (48/84) primary tumors and in 44% (37/84) PDs. At 75% cut-off, 28.6% (24/84) primary tumors and 20.2% (17/84) PDs were CLDN18-positive. The concordance rate between primary tumors and PD was 79.8% at 40% cut-off and 75% at 75% cut-off. When comparing biopsy and surgical specimens, the concordance rates were 87.5% at 40% cut-off and 81.3% at 75% cut-off. Within a tumor, the superficial area tended to have a higher CLDN18-positive rate than the invasive front (P = 0.001). Although HER2 -positivity was only 11.9% in this cohort, CLDN18 positivity in HER2-negative tumors (n = 74) was relatively high: 60.8% at 40% cut-off and 28.4% at 75% cut-off. Among double-negative (HER2 - and PD-L1 CPS < 1) tumors, CLDN18 positivity was 67.6% at 40% cut-off and 26.5% at 75% cut-off.
CLDN18 expression is generally maintained in PD and is relatively high even in double-negative tumors, making it a promising therapeutic target for PD-positive gastric cancer.
伴有腹膜转移（PD）的胃癌预后较差，目前的治疗方法疗效甚微。CLDN18.2 靶向治疗对高表达 CLDN18.2 的胃癌显示出良好的疗效。由于 PD 中 CLDN18.2 状态的信息有限，我们分析了 PD 阳性胃癌中 CLDN18 的状态，包括原发性和 PD 中的 HER2 和 PD-L1 联合阳性评分（CPS）。
使用配对的原发性和 PD 组织样本对 84 例胃癌病例进行免疫组织化学分析。
在 40%的截断值下，CLDN18 在 57%（48/84）的原发性肿瘤和 44%（37/84）的 PD 中呈阳性。在 75%的截断值下，28.6%（24/84）的原发性肿瘤和 20.2%（17/84）的 PD 中 CLDN18 呈阳性。在 40%的截断值下，原发性肿瘤和 PD 之间的一致性率为 79.8%，在 75%的截断值下为 75%。在比较活检和手术标本时，在 40%的截断值下，一致性率为 87.5%，在 75%的截断值下为 81.3%。在肿瘤内部，浅层区域的 CLDN18 阳性率高于浸润前缘（P=0.001）。尽管该队列中 HER2 阳性率仅为 11.9%，但在 HER2 阴性肿瘤（n=74）中，CLDN18 的阳性率相对较高：在 40%的截断值下为 60.8%，在 75%的截断值下为 28.4%。在双阴性（HER2-和 PD-L1 CPS<1）肿瘤中，在 40%的截断值下，CLDN18 的阳性率为 67.6%，在 75%的截断值下为 26.5%。
CLDN18 的表达在 PD 中通常保持不变，即使在双阴性肿瘤中也相对较高，这使其成为 PD 阳性胃癌有前途的治疗靶点。
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