Brain Metastases of Gastro-oesophageal Cancer: Evaluation of Molecules with Relevance for Targeted Therapies

Background: Brain metastases (BM) of gastrooesophageal cancer are exceedingly rare and only limited data exist on their pathobiology. Materials and Methods: We identified tissue samples of BM of gastro-oesophageal cancer and analyzed the expression of human epidermal growth factor receptor-2 (HER2), phosphorylated signal transducer and activator of transcription-3 (pSTAT3), epithelial growth factor receptor (EGFR), V600E point mutation of the v-raf murine sarcoma viral oncogene homolog-B1 (BRAF V600E), cluster of differentiation molecule-34 (CD34), hypoxia inducible factor-la (HIF 1-alpha) and Ki-67 by immunohistochemical methods. Results: Our series comprised of twenty adenocarcinomas and one oesophageal squamous cell carcinoma. Three (14%), 7(33%), 9 (43%), 18 (86%) and 0 BM specimens were scored positively for HER2, EGFR, pSTAT3, HIF1-alpha and BRAF V600E expression. The median Ki-67 index was 59%. The microvascular density was moderate-to-high and active intratumoral microvascular sprouting was evident in 20121 (95%) of BMs. The HER2 and EGFR expression status were consistent between primary tumors and BM in all three assessable cases. HIF1-alpha and pSTAT3 expression were significantly higher in HER2-positive cases. Conclusion: Therapeutic use of agents targeting HER2, pSTAT3, EGFR and angiogenesis may be feasible for selected BM of gastro-esophageal cancer. HER2 positivity does not seem to predispose to brain colonization in gastro-esophageal cancer.