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

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ICR Authors

Valeri, Nicola

Authors

Coati, I
Lotz, G
Fanelli, GN
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
Rugge, M
Kiss, A
Loupakis, F
Fassan, M

Document Type

Journal Article

Date

2019-07-30

Date Accepted

2019-06-05

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.

Citation

British Journal of Cancer, 2019, 121 (3), pp. 257 - 263

DOI

10.1038/s41416-019-0508-4

URI

https://repository.icr.ac.uk/handle/internal/5373

Rights

http://creativecommons.org/licenses/by/4.0/

Source Title

British Journal of Cancer

Publisher

NATURE PUBLISHING GROUP

ISSN

0007-0920

eISSN

1532-1827
1532-1827

Collections

Cancer Biology

Research Team

GI Cancer Biol & Genomics

Notes