title: Leptin, MUC2 and mTOR in appendiceal mucinous neoplasms.
abstract: OBJECTIVE
  Leptin contributes to mucin production in colonic epithelium and regulates carcinogenesis via various signalling pathways. We evaluated the proteins involved in mucin-producing carcinogenesis and putative targets for molecular therapy in appendiceal mucinous neoplasms.
  
  
  METHODS
  Immunohistochemistry and fluorescence in situ hybridization were performed in 22 cases of appendiceal mucinous adenoma, 20 mucinous neoplasms of uncertain malignant potential and 14 mucinous adenocarcinomas.
  
  
  RESULTS
  Leptin, MUC2, MUC5AC, mTOR and ERK were more frequently immunopositive in mucinous adenocarcinomas compared with mucinous adenomas or mucinous neoplasms of uncertain malignant potential (p < 0.05). STAT3 revealed immunopositivity in 82% of tumours, regardless of tumour category. MUC2 immunopositivity was associated with pseudomyxoma peritonei (p < 0.05). None of the tumours exhibited c-kitimmunoexpression, amplification of Her2 or EGFR, or translocation of ALK. The mTOR-immunopositive group of patients had a lower rate of disease-free survival compared with the mTOR-immunonegative group (p < 0.05).
  
  
  CONCLUSIONS
  Leptin may collaborate with MUC2 and MUC5AC in mucin-producing carcinogenesis in an mTOR-, STAT3- and ERK-dependent manner. STAT3 may be activated early during tumorigenesis. MUC2 and mTOR (but not c-kit, Her2, EGFR and ALK) may represent targets for molecular therapy in pseudomyxoma peritonei and appendiceal mucinous adenocarcinoma, respectively.
authors.affiliation: Department of Pathology, Seoul National University Boramae Hospital, Seoul, Korea. meesooch@snu.ac.kr
authors.forename: Mee Soo
authors.initials: MS
authors.lastname: Chang
authors.forename: Sun-ju
authors.initials: SJ
authors.lastname: Byeon
authors.forename: Sun Och
authors.initials: SO
authors.lastname: Yoon
authors.forename: Baek-hui
authors.initials: BH
authors.lastname: Kim
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Kyu Joo
authors.initials: KJ
authors.lastname: Park
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001063:Appendiceal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D020738:Leptin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism; D055262:Mucin-2 / Q000378:metabolism*; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D011553:Pseudomyxoma Peritonei / Q000378:metabolism / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D020738:Leptin; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases