claudin 18.2的临床病理分析，重点关注转移性或不可切除胃癌患者的瘤内异质性和生存

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2024-12-01 DOI:10.1016/j.esmoop.2024.104000

T.-Y. Kim , Y. Kwak , S.K. Nam , D. Han , D.-Y. Oh , S.-A. Im , H.S. Lee

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引用次数: 0

摘要

本研究旨在探讨CLDN18.2 （CLDN18.2）阳性在转移性或不可切除胃癌（GC）中的患病率，特别关注肿瘤内异质性及其与临床病理特征的关系。患者和方法我们调查了400例因不可切除、转移性或复发性胃癌接受全身化疗的患者。进行了CLDN18 （43-14A）、人表皮生长因子受体2 （HER2）、程序性死亡配体1 （PD-L1）和成纤维细胞生长因子受体2的免疫组化，以及HER2银原位杂交（ISH）、eb病毒（EBV） ISH和微卫星不稳定性测试。利用数字图像分析计算CD3+、CD8+、CD4+和foxp3阳性免疫细胞密度。结果在任意表达CLDN18.2的GC病例中，超过一半（61.3%）的病例在四种不同的组织芯片（TMA）中表达结果不同。当比较全组织切片和4个TMA核心的CLDN18.2状态时，85例GC病例中只有2例（2.4%）出现差异，其中1例假阳性，1例假阴性。考虑肿瘤内异质性后，400例胃癌患者中CLDN18.2的阳性率为31.3%。CLDN18.2阳性在位于上颌窦（或下三分之一）和her2阳性的GCs中少见，但在ebv阳性的GCs中很常见(P <；0.05)。CLDN18.2阳性组总生存期（OS）无差异（P = 0.116）。此外，在接受氟嘧啶加铂、化疗加曲妥珠单抗、紫杉醇加或不加ramucirumab和免疫肿瘤药物治疗的患者中，OS和CLDN18.2阳性之间没有关联。cldn18.2阳性/ pd - l1高的GCs的生存期比其他GCs长（P = 0.025），肿瘤中心和周围的CD8+ t细胞密度均较高(P <；0.001)。结论对CLDN18.2阳性表达的不可切除、转移或复发性胃癌进行表征，评估肿瘤内异质性和各种治疗方法的预后意义，有助于改进胃癌患者的治疗策略和开发新的治疗方法。

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Clinicopathological analysis of claudin 18.2 focusing on intratumoral heterogeneity and survival in patients with metastatic or unresectable gastric cancer

Background

This study aimed to investigate the prevalence of claudin 18.2 (CLDN18.2) positivity, with a particular focus on intratumoral heterogeneity, and its association with clinicopathological features in metastatic or unresectable gastric cancer (GC).

Patients and methods

We investigated 400 patients who received systemic chemotherapy for unresectable, metastatic, or recurrent GC. Immunohistochemistry for CLDN18 (43-14A), human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and fibroblast growth factor receptor 2, as well as HER2 silver in situ hybridization (ISH), Epstein–Barr virus (EBV) ISH, and microsatellite instability testing were carried out. CD3+, CD8+, CD4+, and Foxp3-positive immune cell densities were calculated using digital image analysis.

Results

In GC cases with any CLDN18.2 expression, more than half of the cases (61.3%) showed different expression results between four different tissue microarray (TMA) cores. When comparing CLDN18.2 status between whole tissue sections and the combined results from the four TMA cores, discrepancies were observed in only 2 out of 85 GC cases (2.4%), with 1 false positive and 1 false negative. After considering intratumoral heterogeneity, a CLDN18.2 positivity rate of 31.3% was observed among the 400 GC patients. CLDN18.2 positivity was rare in GCs located in the antrum (or lower third) and in HER2-positive cases but was common in EBV-positive GCs (P < 0.05). No differences in overall survival (OS) were observed according to CLDN18.2 positivity (P = 0.116). Additionally, there was no association between OS and CLDN18.2 positivity in patients treated with fluoropyrimidine plus platinum, chemotherapy plus trastuzumab, paclitaxel with or without ramucirumab, and immuno-oncologic agents. CLDN18.2-positive/PD-L1-high GCs showed statistically significantly longer OS than others (P = 0.025) and higher CD8+ T-cell densities in both the tumor center and periphery (P < 0.001).

Conclusions

Characterizing unresectable, metastatic, or recurrent GC with positive CLDN18.2 expression and evaluating intratumoral heterogeneity and prognostic implications of various therapeutics help advance treatment strategies and develop new therapies for patients with GC.

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.