Leptin and mTOR Are Involved in Appendiceal Mucinous Carcinogenesis.
Sun-ju Byun, Sun Och Yoon, Baek-hui Kim, Hye Seung Lee, Gyeong Hoon Kang, Woo Ho Kim, Mee Soo Chang. Seoul National University Boramae Hospital, Republic of Korea; Seoul National University College of Medicine, Republic of Korea; Bundang Seoul National University Hospital, Seoul, Republic of Korea
Background: In appendiceal mucinous neoplasm, a pathological decision on benignancy or malignancy is a challenging task, since extreme low cellularity and undiscerned layers of appendiceal wall occur commonly due to plethora of mucin. Here, we evaluated signal pathways involved in mucin-producing carcinogenesis, and the putative target for molecular therapy in appendiceal mucinous adenocarcinomas.
Design: Appendiceal mucinous neoplasms were classified into three tumor categories; 32 cases of mucinous adenoma, 23 mucinous tumor of unknown malignant potential and 15 mucinous adenocarcinoma. To study signal pathways involved in mucin-producing carcinogenesis, immunohistochemistry for leptin, leptin receptor, pAkt, mTOR, Erk and pSTAT3 was performed. To propose a candidate for molecular therapy, fluorescence in situ hybridization for Her2, EGFR and ALK, and immunohistochemistry for mTOR and c-kit were made. Additionally, the previously published our data on MUC2, MUC5AC and c-kit immunoexpression were excerpted.
Results: The expression of leptin, leptin receptor, MUC2, MUC5AC, mTOR and Erk was increasingly high, in order of adenomas, tumors of uncertain malignant potential and adenocarcinomas (p < 0.05, respectively). The pSTAT was not expressed in normal epithelium, but in tumors irrespective of tumor categories. As for the relation of examined proteins, leptin was correlated with MUC2, MUC5AC and mTOR (p < 0.05, respectively). Univariate analysis showed that mTOR expression was associated with a low rate of disease-free survival of cancer patients (p < 0.05). Besides, none of 70 cases showed Her2 and EGFR amplification, ALK translocation or c-kit overexpression.
Conclusions: The leptin may collaborate with mucin (MUC2, MUC5AC) on carcinogenesis which the mTOR-dependent, the Erk-dependent, and pSTAT-dependent pathways appear to be involved in. The mTOR is suggested as a therapeutic target for appendiceal mucinous adenocarcinomas. However, Her2, EGFR, ALK and c-kit may not be the target for therapy.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 32, Wednesday Morning