IJMS, Vol. 19, Pages 47: Characterizing Metastatic HER2-Positive Gastric Cancer at the CDH1 Haplotype

IJMS, Vol. 19, Pages 47: Characterizing Metastatic HER2-Positive Gastric Cancer at the CDH1 Haplotype

International Journal of Molecular Sciences doi: 10.3390/ijms19010047

Authors: Laura Caggiari Gianmaria Miolo Angela Buonadonna Debora Basile Davide A. Santeufemia Antonio Cossu Giuseppe Palmieri Mariangela De Zorzi Mara Fornasarig Lara Alessandrini Vincenzo Canzonieri Giovanni Lo Re Fabio Puglisi Agostino Steffan Renato Cannizzaro Valli De Re

The CDH1 gene, coding for the E-cadherin protein, is linked to gastric cancer (GC) susceptibility and tumor invasion. The human epidermal growth factor receptor 2 (HER2) is amplified and overexpressed in a portion of GC. HER2 is an established therapeutic target in metastatic GC (mGC). Trastuzumab, in combination with various chemotherapeutic agents, is a standard treatment for these tumors leading to outcome improvement. Unfortunately, the survival benefit is limited to a fraction of patients. The aim of this study was to improve knowledge of the HER2 and the E-cadherin alterations in the context of GC to characterize subtypes of patients that could better benefit from targeted therapy. An association between the P7-CDH1 haplotype, including two polymorphisms (rs16260A-rs1801552T) and a subset of HER2-positive mGC with better prognosis was observed. Results indicated the potential evaluation of CDH1 haplotypes in mGC to stratify patients that will benefit from trastuzumab-based treatments. Moreover, data may have implications to understanding the HER2 and the E-cadherin interactions in vivo and in response to treatments.

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