title: Clinical Significance of NOTCH1 and NOTCH2 Expression in Gastric Carcinomas: An Immunohistochemical Study.
abstract: BACKGROUND
  NOTCH signaling can exert oncogenic or tumor suppressive functions and can contribute to chemotherapy resistance in cancer. In this study, we aimed to clarify the clinicopathological significance and the prognostic and predictive value of NOTCH1 and NOTCH2 expression in gastric cancer (GC).
  
  
  METHODS
  NOTCH1 and NOTCH2 expression was determined immunohistochemically in 142 primarily resected GCs using tissue microarrays and in 84 pretherapeutic biopsies from patients treated by neoadjuvant chemotherapy. The results were correlated with survival, response to therapy, and clinico-pathological features.
  
  
  RESULTS
  Primarily resected patients with NOTCH1-negative tumors demonstrated worse survival. High NOTCH1 expression was associated with early-stage tumors and with significantly increased survival in this subgroup. Higher NOTCH2 expression was associated with early-stage and intestinal-type tumors and with better survival in the subgroup of intestinal-type tumors. In pretherapeutic biopsies, higher NOTCH1 and NOTCH2 expression was more frequent in non-responding patients, but these differences were statistically not significant.
  
  
  CONCLUSIONS
  Our findings suggested that, in particular, NOTCH1 expression indicated good prognosis in GC. The close relationship of high NOTCH1 and NOTCH2 expression with early tumor stages may indicate a tumor-suppressive role of NOTCH signaling in GC. The role of NOTCH1 and NOTCH2 in neoadjuvantly treated GC is limited.
authors.affiliation: Institute of Pathology, Technische Universität München , Munich , Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Bauer
authors.affiliation: Institute of Pathology, Technische Universität München , Munich , Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Takacs
authors.affiliation: Institute of Pathology, Technische Universität München , Munich , Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Slotta-Huspenina
authors.affiliation: Department of Pathology, University of Bern , Bern , Switzerland.
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.affiliation: Institute of Pathology, Technische Universität München , Munich , Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Becker
authors.affiliation: Department of Surgery, Technische Universität München , Munich , Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Novotny
authors.affiliation: Department of Surgery, Klinikum Rosenheim , Rosenheim , Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Ott
authors.affiliation: Institute of Pathology, Helmholtz-Zentrum München , Neuherberg , Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.affiliation: Institute of Medical Statistics and Epidemiology, Technische Universität München , Munich , Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hapfelmeier
authors.affiliation: Institute of Pathology, Technische Universität München , Munich , Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Keller
keywords: chemotherapy; immunohistochemistry; prognosis; receptor NOTCH1; receptor NOTCH2; stomach neoplasms