Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled cases

Irene Coati, Gábor Lotz, Giuseppe Nicolò Fanelli, Stefano Brignola, Cristiano Lanza, Rocco Cappellesso, Antonio Pellino, Salvatore Pucciarelli, Gaya Spolverato, Vincenza Guzzardo, Giada Munari, Giovanni Zaninotto, Marco Scarpa, Luca Mastracci, Fabio Farinati, Stefano Realdon, Pierluigi Pilati, Sara Lonardi, Nicola Valeri, Massimo RuggeAndras Kiss, Fotios Loupakis, Matteo Fassan

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Abstract

Background: Claudin-18 (CLDN18) is a highly specific tight junction protein of the gastric mucosa. An isoform of CLDN18, the Claudin 18.2, has recently emerged as an innovative drug target for metastatic gastric cancer. Methods: We investigated the immunohistochemical profile of CLDN18, p53, p16, E-cadherin, MSH2, MSH6, MLH1, PSM2, HER2, and PDL-1 in a large series of 523 primary gastric carcinomas (GCs; n = 408) and gastro-oesophageal carcinomas (GECs; n = 115) and 135 matched and synchronous nodal metastases. The status of HER2 and EBER by means of chromogenic in situ hybridisation (CISH) was also evaluated. Results: High membranous CLDN18 expression was present in 150/510 (29.4%) primary cases and in 45/132 (34.1%) metastases. An abnormal expression (i.e. nuclear and/or cytoplasmic) was observed in 115 (22.5%) primary cases and in 33 (25.0%) metastases. A 38.8% of the cases showed significant CLDN18 intratumoural variability among the different tissue microarray cores obtained from the same tumour. Positive membrane CLDN18 expression was statistically associated with non-antral GCs (p = 0.016), Lauren diffuse type (p = 0.009), and with EBV-associated cancers (p < 0.001). Conclusions: CLDN18 is frequently expressed in gastric and gastro-oesophageal cancers; further studies should investigate the prognostic significance of CLDN18 heterogeneity in order to implement its test into clinical practice.

Original languageEnglish
Pages (from-to)257-263
Number of pages7
JournalBritish journal of cancer
Volume121
Issue number3
DOIs
Publication statusPublished - Jul 30 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Coati, I., Lotz, G., Fanelli, G. N., Brignola, S., Lanza, C., Cappellesso, R., Pellino, A., Pucciarelli, S., Spolverato, G., Guzzardo, V., Munari, G., Zaninotto, G., Scarpa, M., Mastracci, L., Farinati, F., Realdon, S., Pilati, P., Lonardi, S., Valeri, N., ... Fassan, M. (2019). Claudin-18 expression in oesophagogastric adenocarcinomas: a tissue microarray study of 523 molecularly profiled cases. British journal of cancer, 121(3), 257-263. https://doi.org/10.1038/s41416-019-0508-4