Leptin, MUC2 and mTOR in appendiceal mucinous neoplasms

Mee Soo Chang, Sun Ju Byeon, Sun Och Yoon, Baek-Hui Kim, Hye Seung Lee, Gyeong Hoon Kang, Woo Ho Kim, Kyu Joo Park

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14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)45-53
Number of pages9
JournalPathobiology
Volume79
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1
Externally publishedYes

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Keywords

  • Appendiceal mucinous neoplasm
  • ERK
  • Leptin
  • mTOR
  • MUC2
  • MUC5AC
  • STAT3

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Chang, M. S., Byeon, S. J., Yoon, S. O., Kim, B-H., Lee, H. S., Kang, G. H., Kim, W. H., & Park, K. J. (2012). Leptin, MUC2 and mTOR in appendiceal mucinous neoplasms. Pathobiology, 79(1), 45-53. https://doi.org/10.1159/000332739