Abstract P6-05-11: Leptin and Leptin receptor expression in human breast cancer

Abstract

Abstract INTRODUCTION: Leptin is a protein that plays a key role in regulating energy intake and energy expenditure, including appetite and metabolism. It is one of the most important adipose derived hormones and has been suggested to act as a growth factor in neoplasms. Obesity has been linked to increased risk of breast cancer in postmenopausal women. Increased peripheral production of oestrogen has been regarded as the main cause for this association, but other factors affecting fat metabolism may be implicated. There is recent evidence that Leptin stimulates cancer cell proliferation in MCF-7 cancer cells. Both Cox2 and hTERT have been proposed as mediators of Leptin's carcinogenic role. Our objective was to determine, using quantitative PCR, whether the mRNA expression levels of Leptin and Leptin receptor were consistent with a tumour proliferative function and whether levels from these genes were positively correlated with clinical outcome in breast cancer. METHODS: A total of 153 samples were analysed. The levels of transcription of Leptin and its receptor were determined using quantitative PCR and normalised against (CK19). Transcript levels within breast cancer specimens were compared to normal background tissues and analysed against conventional pathological parameters and clinical outcome over a 10 year follow-up period. RESULTS: The levels of Leptin and Leptin receptor mRNA were significantly higher in malignant samples (p = 0.0011 and 0.0014 respectively). This difference remained statistically significant when comparing levels between normal samples and all malignant subgroups according to their NPI, grade, stage, local recurrence, and distant metastasis in both ER receptor positive and negative samples. It was also present across all histological types for both Leptin and its receptor. There was no significant change in mRNA transcription levels correlating with tumour grade, stage, disease free survival, or development of loco regional recurrence. There was also no statistically significant difference in levels of expression of both Leptin and its receptor when comparing ER positive to negative patients (p = 0.74 and 0.27 respectively). Leptin levels showed a significantly positive correlation with Leptin receptors (r = 0.504, 0.0000000222). We have observed no significant correlations between Leptin and hTERT or Cox2. CONCLUSION: This study demonstrates compelling evidence that both Leptin and Leptin receptor mRNA transcription levels are more readily expressed in cancerous tissues providing further evidence that it plays a significant role in the process of breast carcinogenesis. However, Leptin levels did nor correlate with tumor's stage, clinical outcome, hTERT or Cox-2 levels. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-05-11.