| Autor: |
Bencivenga M; General and Upper GI Surgery, Department of Surgery, Verona University, 37126 Verona, Italy., Torroni L; General and Upper GI Surgery, Department of Surgery, Verona University, 37126 Verona, Italy.; Unit of Epidemiology and Medical Statistics, Department of Diagnostic and Public Health, University of Verona, 37134 Verona, Italy., Dal Cero M; General and Upper GI Surgery, Department of Surgery, Verona University, 37126 Verona, Italy.; Section of Gastrointestinal Surgery, Hospital del Mar, Hospital del Mar Medical Research Institute (IMIM), Department of Surgery, Universitat Autonoma de Barcelona, 08003 Barcelona, Spain., Quinzii A; Investigational Cancer Therapeutics Clinical Unit, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy.; Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, 37134 Verona, Italy., Zecchetto C; Investigational Cancer Therapeutics Clinical Unit, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy.; Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, 37134 Verona, Italy., Merz V; Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, 37134 Verona, Italy., Casalino S; Investigational Cancer Therapeutics Clinical Unit, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy.; Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, 37134 Verona, Italy., Taus F; Unit of Epidemiology and Medical Statistics, Department of Diagnostic and Public Health, University of Verona, 37134 Verona, Italy.; Unit of Forensic Medicine, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy., Pietrobono S; Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, 37134 Verona, Italy., Mangiameli D; Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, 37134 Verona, Italy., Filippini F; General and Upper GI Surgery, Department of Surgery, Verona University, 37126 Verona, Italy., Alloggio M; General and Upper GI Surgery, Department of Surgery, Verona University, 37126 Verona, Italy., Castelli C; Anatomical Pathology Unit, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy., Iglesias M; Department of Pathology, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain., Pera M; Section of Gastrointestinal Surgery, Hospital del Mar, Hospital del Mar Medical Research Institute (IMIM), Department of Surgery, Universitat Autonoma de Barcelona, 08003 Barcelona, Spain., Melisi D; Investigational Cancer Therapeutics Clinical Unit, Azienda Ospedaliera Universitaria Integrata, 37134 Verona, Italy.; Digestive Molecular Clinical Oncology Research Unit, Università degli Studi di Verona, 37134 Verona, Italy. |
| Abstrakt: |
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 <10% of cells) and high nuclear expression (≥10% of cells). Women represented about half of the present series (52%), and the median age was 64 years (p25-p75 range: 53-75). Neoadjuvant and adjuvant treatments were administered to 10% and 54% of the cases, respectively. Extended systemic lymphadenectomy (D2) was the most common (54%). In nearly all cases, the number of retrieved nodes was ≥15, i.e., adequate for tumor staging (94%). An R0 resection was achieved in 80% of the cases. Most patients were pathological T stage 3 and 4 (pT3/pT4 = 79.0%) and pathological N stage 2, 3a, and 3b (pN2/pN3a/pN3b = 47.0%) at the pathological examination. Twenty patients (15%) presented distant metastases. Five-year overall survival (OS) was significantly higher ( 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. |
