HER2 status in unusual histological variants of gastric adenocarcinomas

Aim To investigate HER2 status in a cohort of 109 gastric adenocarcinomas also including unusual variants, such as 14 hepatoid (HAS) and 9 mitochondrion-rich (MRC), characterised by an opposing clinical behaviour.Methods and Results Using HercepTest (DAKO) and FISH test (pharmDx DAKO), HER2 overexpression/amplification was encountered in 23 of 109 (21.10%) of all gastric adenocarcinomas. A progressive increase in HER2 overexpression was observed moving from the poorly cohesive histotype to MRC, tubular adenocarcinomas and HAS. A statistically significant difference was found between poorly cohesive carcinomas and the others; a similar significant difference was encountered between HAS and all other variants of adenocarcinoma. HER2 overexpression was significantly associated with high grade, advanced stage, high Ki-67 labelling index value and death from gastric cancer. Multivariate analysis identified HER2 overexpression as an independent unfavourable prognostic variable for adenocarcinomas as a whole and also for the HAS variant.Conclusions Trastuzumab has been confirmed as an additional useful therapeutic standard option for patients with HER2-positive advanced gastric cancers, and also in aggressive variants of adenocarcinomas such as HAS.