Leptin, MUC2 and mTOR in appendiceal mucinous neoplasms

Mee Soo Chang, Sun Ju Byeon, Sun Och Yoon, Baek Hui Kim, Hye Seung Lee, Gyeonghoon 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
StatePublished - 1 Jan 2012

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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
  • MUC2
  • MUC5AC
  • STAT3
  • mTOR

Cite this

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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.",
keywords = "Appendiceal mucinous neoplasm, ERK, Leptin, MUC2, MUC5AC, STAT3, mTOR",
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Leptin, MUC2 and mTOR in appendiceal mucinous neoplasms. / Chang, Mee Soo; Byeon, Sun Ju; Yoon, Sun Och; Kim, Baek Hui; Lee, Hye Seung; Kang, Gyeonghoon; Kim, Woo Ho; Park, Kyu Joo.

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

Research output: Contribution to journalArticle

TY - JOUR

T1 - Leptin, MUC2 and mTOR in appendiceal mucinous neoplasms

AU - Chang, Mee Soo

AU - Byeon, Sun Ju

AU - Yoon, Sun Och

AU - Kim, Baek Hui

AU - Lee, Hye Seung

AU - Kang, Gyeonghoon

AU - Kim, Woo Ho

AU - Park, Kyu Joo

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

AB - 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.

KW - Appendiceal mucinous neoplasm

KW - ERK

KW - Leptin

KW - MUC2

KW - MUC5AC

KW - STAT3

KW - mTOR

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DO - 10.1159/000332739

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VL - 79

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