title: Notch3 signaling is associated with MUC5AC expression and favorable prognosis in patients with small intestinal adenocarcinomas.
abstract: BACKGROUND
  Notch signaling plays diverse roles not only in physiologic processes, including development and differentiation but also in tumorigenesis, either as a tumor promoter or suppressor depending on the cellular context, level of expression and cross-talk with other signaling pathways. In this study we investigated the expression of Notch3 and MUC proteins and their clinicopathological significance in small intestinal adenocarcinoma (SIAC).
  
  
  METHODS
  Surgically resected 191 SIACs and their clinical data were collected. Immunohistochemistry for Notch3, MUC2, MUC5AC, and MUC6 using tissue microarrays from formalin-fixed paraffin-embedded normal and matched tumor tissues was performed.
  
  
  RESULTS
  Notch3 expression was found in 52 (29.9%) cases of the tumors. MUC2, MUC5AC, and MUC6 were expressed in 52 (27.5%), 51 (31.9%), and 42 (22.0%) cases of the tumor, respectively. Notch3 expression was correlated with the absence of lymphovascular invasion (p=0.009), lower T stage (p=0.038), and histological subtype of tubular adenocarcinoma (p=0.01), respectively. MUC2 was correlated with large tumor size (p=0.013) and mucinous and signet ring cell adenocarcinomas (p=0.01). MUC5A was correlated with proximal tumor location (p<0.0001) and tumor differentiation (p=0.027). MUC6 was correlated with proximal tumor location (p<0.0001) and lower pT stage (p=0.009), and absence of lymphovascular invasion, respectively. A significant correlation was noted between Notch3 and MUC5AC expression (p=0.019). Notch3 expression was a relatively favorable prognostic factor in SIACs by univariate (p=0.05) and multivariate analysis (p=0.08, Cox Hazard ratio 0.841).
  
  
  CONCLUSIONS
  Our findings indicate that Notch3 signaling, associated with MUC5AC expression, could be a more favorable prognostic factor in SIACs.
authors.affiliation: Department of Pathology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea. Electronic address: edwjyh@gnah.co.kr.
authors.forename: Dae-Woon
authors.initials: DW
authors.lastname: Eom
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Seung-Mo
authors.initials: SM
authors.lastname: Hong
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Jihun
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Pathology, Bundang CHA Medical Center, CHA University, Seongnam, Republic of Korea.
authors.forename: Gwangil
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Pathology, Yeungnam University College of Medicine, Daegu, Republic of Korea.
authors.forename: Young Kyung
authors.initials: YK
authors.lastname: Bae
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kee-Taek
authors.initials: KT
authors.lastname: Jang
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Eunsil
authors.initials: E
authors.lastname: Yu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism*; D055262:Mucin-2 / Q000378:metabolism; D055272:Mucin-6 / Q000378:metabolism; D011379:Prognosis; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C524625:MUC2 protein, human; C524678:MUC5AC protein, human; C524734:MUC6 protein, human; D055271:Mucin 5AC; D055262:Mucin-2; D055272:Mucin-6; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch
keywords: Adenocarcinoma; MUC5AC; Notch3; Prognosis; Small intestine