Leptin Expression Correlates with Favorable Clinicopathologic Phenotype and Better Prognosis in Colorectal Adenocarcinoma
W Na, SM Jang, KS Jang, KH Lee, DH Choi, SJ Jang, SS Paik. College of Medicine, Hanyang University, Seoul, Republic of Korea; Armed Forces Capital Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea; College of Medicine, Soon Chun Hyang University, Seoul, Republic of Korea; Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea
Background: Leptin, the product of the ob gene, is an adipocyte-derived neurohormone that regulates body fat storage and feeding behavior. Some studies have suggested that leptin has growth factor-like functions in epithelial cells and its abnormal expression may be involved in cancer development and progression. We investigated the leptin expression in normal and neoplastic colorectal tissues and their association with the clinicopathological features and clinical outcome in colorectal adenocarcinoma patients.
Design: Leptin expression was evaluated on the tissue microarray of 44 normal colon mucosal tissues, 44 adenomatous polyps and 437 colorectal adenocarcinomas by immunohistochemistry. Data was analyzed by chi-square test, one-way ANOVA, Cox regression hazards model and log-rank test with Kaplan-Meier curves.
Results: Frequency of leptin expression was dramatically increased from normal colonic mucosa (2/44, 4.5%) to adenomas (13/44, 29.5%) and adenocarcinomas (321/437, 73.5%) as neoplastic progression. Interestingly, leptin expression was correlated with favorable tumor features in depth of invasion (p = 0.002), lymph node metastasis (p = 0.041), AJCC and Dukes' stage (p = 0.005 and p = 0.002, respectively), differentiation (p = 0.002) and lymphatic invasion (p = 0.010). In univariate survival analysis, patients with leptin positive adenocarcinoma revealed better overall and disease-free survivals (p = 0.032 and p = 0.004, respectively, log-rank test). In multivariate survival analysis with the Cox proportional hazards model, leptin expression was an independent prognostic marker of disease-free survival (p = 0.009).
Conclusions: Leptin was gradually expressed during the normal-adenoma-adenocarcinoma sequence, suggesting an association in colorectal carcinogenesis. In addition, high leptin expression was an indicator of favorable tumor features and better survival of colorectal cancer patients.
Monday, March 9, 2009 1:00 PM
Poster Session II # 82, Monday Afternoon