title: Leptin expression correlates with favorable clinicopathologic phenotype and better prognosis in colorectal adenocarcinoma.
abstract: 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 leptin expression in normal and neoplastic colorectal tissues and its association with clinicopathological features and clinical outcome in colorectal adenocarcinoma patients. Leptin expression was evaluated on the tissue microarray of 44 normal colon mucosal tissues, 44 adenomatous polyps, and 437 colorectal adenocarcinomas by immunohistochemistry. Data were analyzed by chi-square test, one-way analysis of variance (ANOVA), Cox regression hazards model, and log-rank test with Kaplan-Meier curves. 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 = 0.033), lymph node metastasis (p = 0.019), American Joint Committee on Cancer (AJCC) and Dukes' stage (p = 0.021 and p = 0.005, respectively), differentiation (p = 0.010), and lymphatic invasion (p = 0.003). 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 Cox proportional hazards model, leptin expression was an independent prognostic marker of disease-free survival (p = 0.009). We conclude that 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.
authors.affiliation: Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea.
authors.forename: Seung Sam
authors.initials: SS
authors.lastname: Paik
authors.forename: Se-Min
authors.initials: SM
authors.lastname: Jang
authors.forename: Ki-Seok
authors.initials: KS
authors.lastname: Jang
authors.forename: Kang Hong
authors.initials: KH
authors.lastname: Lee
authors.forename: Dongho
authors.initials: D
authors.lastname: Choi
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D018256:Adenomatous Polyps / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D020738:Leptin / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D015996:Survival Rate; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D020738:Leptin