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

Research output: Contribution to journalArticle

13 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

Fingerprint

Appendiceal Neoplasms
Leptin
Mucinous Adenocarcinoma
Carcinogenesis
Mucins
Pseudomyxoma Peritonei
Neoplasms
Adenoma
Fluorescence In Situ Hybridization
Disease-Free Survival
Epithelium
Immunohistochemistry
Therapeutics

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., ... Park, K. J. (2012). Leptin, MUC2 and mTOR in appendiceal mucinous neoplasms. Pathobiology, 79(1), 45-53. https://doi.org/10.1159/000332739

Leptin, MUC2 and mTOR in appendiceal mucinous neoplasms. / Chang, Mee Soo; Byeon, Sun Ju; Yoon, Sun Och; Kim, Baek-Hui; Lee, Hye Seung; Kang, Gyeong Hoon; Kim, Woo Ho; Park, Kyu Joo.

In: Pathobiology, Vol. 79, No. 1, 01.01.2012, p. 45-53.

Research output: Contribution to journalArticle

Chang, MS, Byeon, SJ, Yoon, SO, Kim, B-H, Lee, HS, Kang, GH, Kim, WH & Park, KJ 2012, 'Leptin, MUC2 and mTOR in appendiceal mucinous neoplasms', Pathobiology, vol. 79, no. 1, pp. 45-53. https://doi.org/10.1159/000332739
Chang MS, Byeon SJ, Yoon SO, Kim B-H, Lee HS, Kang GH et al. Leptin, MUC2 and mTOR in appendiceal mucinous neoplasms. Pathobiology. 2012 Jan 1;79(1):45-53. https://doi.org/10.1159/000332739
Chang, Mee Soo ; Byeon, Sun Ju ; Yoon, Sun Och ; Kim, Baek-Hui ; Lee, Hye Seung ; Kang, Gyeong Hoon ; Kim, Woo Ho ; Park, Kyu Joo. / Leptin, MUC2 and mTOR in appendiceal mucinous neoplasms. In: Pathobiology. 2012 ; Vol. 79, No. 1. pp. 45-53.
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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.",
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