Central Nervous System metastastasis in gastric or gastro-esophageal junction cancer, correlation with human epidermal growth factor 2 (HER-2) status

Abstract

Background: Central nervous system (CNS) metastases from the gastrointestinal tract (GIT) cancers are relatively rare, and occur in 0.16-0.69% of the patients with gastric cancer. Overexpression of the human epidermal growth factor 2 (HER2) is associated with a aggressive metastatic phenotype poor prognosis, in the absence of HER2 targeted-therapy, and increased incidence of CNS metastases in patients with breast cancer. However, the role of HER2 overexpression in CNS metastatizing is not so well-characterized in gastric, or gastroesophageal adenocarcinoma. The purpose of this retrospective study is to assess the incidence of CNS metastases in patients with gastric cancer and to evaluate the relation of CNS metastases with HER2 status. Patients and Methods: Between 2007 and 2013, 300 patients with gastric cancer were admitted to the general hospital of Piacenza (Italy). These cases were retrospectively analyzed to evaluate CNS metastases. The metastases were diagnosed on imaging techniques performed in symptomatic patients. Histological samples of patients with CNS metastases were reviewed and tested for HER2, and patients were considered to have HER2 positive gastric cancer if the their tumor samples were scored as 3+ on immunohistochemistry or if they were fluorescence in situ hybridization (FISH) positive performed in case with 2+ on IHC. Result(s): Seven of 300 patients (2.33 %) with gastric cancer were found to have CNS metastases on imaging studies and six out of seven (85.71 %) patients with gastric cancer and CNS metastases, had HER2 positive disease. These patients showed also an advanced initial disease, a more aggressive behaviour and poor prognosis with a median overall survival of 4.1 months (range 2.1-6.6 months). Conclusion(s): Despite the limitations of a retrospective study, these results suggest that there is a CNS recurrence susceptibility in patients with HER2 positive gastric cancer. To the best of our knowledge this is the first report that correlates CNS metastases and HER2 status in gastric cancer.