Comparison of East-Asia and West-Europe cohorts explains disparities in survival outcomes and highlights predictive biomarkers of early gastric cancer aggressiveness.

Surgical resection with lymphadenectomy and peri-operative chemotherapy is the universal mainstay for curative treatment of gastric cancer (GC) patients with loco-regional disease. However, GC survival remains asymmetric in West- and East-world regions. We hypothesize this asymmetry derives from differential clinical management. Therefore, we collected chemo-naive GC patients from Portugal and South-Korea to explore specific immunophenotypic profiles related to disease aggressiveness, and clinicopathological factors potentially explaining associated overall survival (OS) differences. Clinicopathological and survival data were collected from chemo-naive surgical cohorts from Portugal (West-Europe cohort (WE-C); n=170) and South-Korea (East-Asia cohort (EA-C); n=367), and correlated with immunohistochemical expression profiles of E-cadherin and CD44v6 obtained from consecutive tissue microarrays sections. Survival analysis revealed a subset of 12.4% of WE-C patients, whose tumors concomitantly express E-cadherin_abnormal and CD44v6_very-high, displaying extremely poor OS, even at TNM stages I and II. These WE-C stages I and II patients were particularly aggressive compared to all other, invading deeper into the gastric wall (p=0.032) and more often permeating the vasculature (p=0.018) and nerves (p=0.009). A similar immunophenotypic profile was found in 11.9% of EA-C patients, but unrelated to survival. Stage I and II EA-C patients displaying both biomarkers also permeated more lymphatic vessels (p=0.003), promoting lymph node (LN) metastasis (p=0.019), being diagnosed on average 8-years earlier and submitted to more extensive LN dissection than WE-C. Concomitant E-cadherin_abnormal/CD44v6_very-high expression predicts aggressiveness and poor survival of stage I and II GC submitted to conservative lymphadenectomy.