TY - JOUR
T1 - Claudin-18 expression in oesophagogastric adenocarcinomas
T2 - a tissue microarray study of 523 molecularly profiled cases
AU - Coati, Irene
AU - Lotz, Gábor
AU - Fanelli, Giuseppe Nicolò
AU - Brignola, Stefano
AU - Lanza, Cristiano
AU - Cappellesso, Rocco
AU - Pellino, Antonio
AU - Pucciarelli, Salvatore
AU - Spolverato, Gaya
AU - Guzzardo, Vincenza
AU - Munari, Giada
AU - Zaninotto, Giovanni
AU - Scarpa, Marco
AU - Mastracci, Luca
AU - Farinati, Fabio
AU - Realdon, Stefano
AU - Pilati, Pierluigi
AU - Lonardi, Sara
AU - Valeri, Nicola
AU - Rugge, Massimo
AU - Kiss, Andras
AU - Loupakis, Fotios
AU - Fassan, Matteo
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
U2 - 10.1038/s41416-019-0508-4
DO - 10.1038/s41416-019-0508-4
M3 - Article
C2 - 31235864
VL - 121
SP - 257
EP - 263
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 3
ER -