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Brief description/objective

BACKGROUND

Metastatic upper gastrointestinal cancer is associated with a poor prognosis and the mainstay of treatement is systemic chemotherapy regardless of underlying histology. While the most frequent sites of metastatic seed are determined by the pathological description of the tumor – intestinal type favors liver and diffuse type is associated with peritoneal spread (Lauren PA et al 1993), gastric cancer may in rarer instances metastasize to less notorious places such as bone, skin, muscle and even the brain (Oh SY et al 2009; York JE et al 1999). The mechanisms underlying these clinical observations are thus far incompletely understood and clinical use of prognostic markers such as E-cadherin (Chen HC 2003 Graziano F 2004) speculative.
Recently the TOGA-Trial, a phase III trial restricted to patients with mainly intestinal-type metastatic gastric cancer overexpressing HER-2, a member of the epidermal growth factor receptor (EGFR)-family, reported a statistically significant improvement in overall survival when combining the EGFR-inhibitor trastuzumab with a standard chemotherapy backbone comprising cisplatin and a fluoropyrimidine (Bang Y et al 2010). Moreover this trial provided for the first time evidence that classical morphology in combination with molecular markers is clinically relevant in UGI-cancer.
In metastatic breast cancer, where HER-2 expression status constitutes a well-known predictive marker for the erb2/HER-2 receptor inhibitor trastuzumab, brain metastasis has been associated with HER-2 positivity (Pestalozzi BC et al 2006). Whether these correlative findings simply correspond to the prolonged course of disease due the the efficacy of the trastuzumab or unveil the brain as a trastuzumab sanctuary or indeed constitute a homing signal to the brain, is part of an ongoing debate.
Given the clinical relevance of the TOGA trial, the question of a possible role of HER-2 in brain metastasis of gastric cancer are pressing because of their therapeutic relevance.


HYPOTHESIS

We hypothesized that HER-2 positivity might be associated with UGI cancer metastatic to the brain. We further speculated that in younger patients (< 40 years), loss of E-Cadherin might be more prevalent in this patient subset (Chen HC et al 2003)