Poorly cohesive (PC) gastric cancer (GC) is extremely aggressive in progression, and there is an urgent need to identify the molecular pathways involved. We hypothesized the essential role of the RhoA–YAP axis in these mechanisms. The present observational multicenter retrospective study included 133 patients with PC GC treated at two dedicated European surgical centers between 2004 and 2014. YAP nuclear localization was measured by immunohistochemical (IHC) analysis of tissue biopsies. The complete absence of nuclear reactivity was coded as negative expression; we considered “any positive” as low nuclear expression (>0% but p = 0.029) in patients with negative YAP (46%, 95% CI 31.1–60.0%) than in the other patients (27%, 17.5–38.1%). Moreover, when controlling for sex, age, pT, pN, and percentage of signet ring cells in the multivariable analysis, YAP expression was a significant predictor of OS (HR 2.03, 95% CI: 1.18–3.51, p = 0.011). Our results provide new insights into the role of the YAP signaling cascade, as its activation was associated with a worse prognosis in PC GC.
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