Prognostic impact of Claudin 18.2 in gastric and esophageal adenocarcinomas
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BRIEF RESEARCH ARTICLE
Prognostic impact of Claudin 18.2 in gastric and esophageal adenocarcinomas A. Arnold1 · S. Daum2,3 · M. von Winterfeld4 · E. Berg1 · M. Hummel1 · B. Rau5 · U. Stein6,7 · C. Treese2,3,6 Received: 20 April 2020 / Accepted: 9 May 2020 © The Author(s) 2020
Abstract Introduction The tight junction molecule Claudin 18.2 is selectively expressed in healthy and malignant gastric epithelial tissue and is a promising therapy target for high Claudin 18.2 expressing adenocarcinomas of the esophagogastric junction and stomach (AEG/S). Methods This study analyzed the prevalence, characteristics and prognostic impact of Claudin 18.2 expression in primary tumor, lymph node and distant metastasis in a large Caucasian AGE/S cohort with 414 patients. Results Claudin 18.2 was highly expressed in 17.1% of primary tumors, 26.7% of lymph node metastasis and 16.7% of distant metastasis. High Claudin 18.2 expression in lymph node metastasis and primary tumors correlated significantly (p 50% positive tumor cells, intensity 2 +) of Claudin 18.2 in only two patients (0.4%). The most recent study from Caoti et al. using clone 34H14L15 and including a cohort of 523 AEG/S patients detected high Claudin expression in 29.4% of patients. Moreover, in their study Claudin 18.2. expression was correlated with a diffuse histologic subtype, corpus localization and EBV-associated subtype [9]. In summary, Claudin 18.2 is a tight junction molecule selectively expressed in gastric epithelial cells and seems to be a promising target in AEG/S. Although Claudin 18.2 has been thoroughly characterized, solid survival data that are crucial for the analysis of the prognostic impact of Claudin 18.2 are still missing. This study analyzes the prognostic impact of Claudin 18.2 expression in a large retrospective AEG/S cohort with a long follow-up time. Furthermore, we compared both antibodies, clone 43-14A applied in the FAST trial and in the ongoing SPOTLIGHT trial as well as the clone EPR19202, used by Dottermusch et al., to understand the differences in expression frequency of the previous studies.
Materials and methods Patients Clinical data from 414 patients with AEG/s of all tumor stages, primarily treated by surgery between 1992 and 2004 at the Charité—Universitätsmedizin Berlin, were collected retrospectively. The mean follow-up was 121.7 months (95% CI 113.9–129.5). The data including patient characteristics and follow-up information were retrieved from the patient management software
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Clinical and Translational Oncology
(SAP®) and the regional population-based cancer registry (“Gemeinsames Krebsregister”) and are summarized in Table 1. This study was approved by the Institutional Review Board of the Charité (EA4/115/10).
Tissue samples Out of FFPE tumor samples from 414 patients (primary tumors n = 392, synchronous lymph node metastasis n = 151 and synchronous distant metastasis n = 40), tissue-micro arrays (TMA) were engineered and analyzed histomorphologically as described before [10]. Immunohistochemical analysis was
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