Relationships between hypoxia markers and the leptin system, estrogen receptors in human primary and metastatic breast cancer: effects of preoperative chemotherapy

BMC Cancer

Research Article

Mariusz Koda¹  Stanislaw Sulkowski¹  Mariola Sulkowska¹  Luiza Kanczuga-Koda¹  Eva Surmacz² 

[1] Department of Pathology, Medical University of Bialystok, Bialystok, Poland;Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, USA;

关键词: Breast Cancer;    Metastatic Breast Cancer;    Hypoxic Condition;    Primary Breast Cancer;    Preoperative Chemotherapy;   

DOI  :  10.1186/1471-2407-10-320

 received in 2009-09-04, accepted in 2010-06-22,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundTumor hypoxia is marked by enhanced expression of hypoxia-inducible factor-α (HIF-1α) and glucose transporter-1 (Glut-1). Hypoxic conditions have also been associated with overexpression of angiogenic factors, such as leptin. The aim of our study was to analyze the relationships between hypoxia markers HIF-1α, Glut-1, leptin, leptin receptor (ObR) and other breast cancer biomarkers in primary and metastatic breast cancer in patients treated or untreated with preoperative chemotherapy.MethodsThe expression of different biomarkers was examined by immunohistochemistry in 116 primary breast cancers and 65 lymph node metastases. Forty five of these samples were obtained form patients who received preoperative chemotherapy and 71 from untreated patients.ResultsIn primary tumors without preoperative chemotherapy, HIF-1α and Glut-1 were positively correlated (p = 0.02, r = 0.437). HIF-1α in primary and metastatic tumors without preoperative therapy positively correlated with leptin (p < 0.0001, r = 0.532; p = 0.013, r = 0.533, respectively) and ObR (p = 0.002, r = 0.319; p = 0.083, r = 0.387, respectively). Hypoxia markers HIF-1α and Glut-1 were negatively associated with estrogen receptor alpha (ERα) and positively correlated with estrogen receptor beta (ERβ). In this group of tumors, a positive correlation between Glut-1 and proliferation marker Ki-67 (p = 0.017, r = 0.433) was noted. The associations between HIF-1α and Glut-1, HIF-1α and leptin, HIF-1α and ERα as well as Glut-1 and ERβ were lost following preoperative chemotherapy.ConclusionsIntratumoral hypoxia in breast cancer is marked by coordinated expression of such markers as HIF-1α, Glut-1, leptin and ObR. The relationships among these proteins can be altered by preoperative chemotherapy.

【 授权许可】

CC BY   
© Koda et al; licensee BioMed Central Ltd. 2010