Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer.
OBJECTIVE
To evaluate leptin and leptin receptor (OB-R) expression in human breast cancer and determine whether it could be effective for the prevention and treatment of breast cancer.


METHODS
Immunohistochemical staining using specific antibodies was used to evaluate the protein expression of leptin and OB-R in 76 invasive ductal carcinomas and 32 samples of corresponding normal mammary gland, and the relationship between the expression of OB-R and leptin and clinicopathological features was analyzed.


RESULTS
Normal mammary epithelial cells did not express a significant level of Ob-R, whereas carcinoma cells showed positive staining for OB-R in 63 (83%) cases. Both normal epithelial cells and carcinoma cells expressed a significant level of leptin. However, overexpression of leptin, as determined by staining intensity, was observed in 70 cancers (92%) but in no normal epithelium. The expression of OB-R showed a significant correlation with the level of leptin expression. Interestingly, distant metastasis was detected in 21 (34%) of 61 OB-R-positive tumors with leptin overexpression, but in none of the 15 tumors that lacked OB-R expression or leptin overexpression (P < 0.05). Consequently, patients with the former tumors showed significantly lower survival than those with the latter.


CONCLUSIONS
Leptin may have a promoting effect on the carcinogenesis and metastasis of breast cancer, possibly in an autocrine manner. Functional inhibition of leptin may be effective for the prevention and treatment of breast cancer.
Ishikawa
Makoto
M
Department of Surgery, Division of Surgical Oncology, The University of Tokyo, Tokyo, Japan. makoto-ishi@umin.ac.jp
Kitayama
Joji
J
Nagawa
Hirokazu
H
D000273:Adipose Tissue; D000328:Adult; D000368:Aged; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D044584:Carcinoma, Ductal / Q000378:metabolism; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020738:Leptin / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D042361:Mammary Glands, Human / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D054411:Receptors, Leptin; D012306:Risk; D013997:Time Factors
C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin