3953

LEPR

leptin receptor;LEPR;leptin receptor

OB receptor|huB219

1p31

protein-coding

PURPOSE: 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. EXPERIMENTAL DESIGN: 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.

BACKGROUND: Epidemiologic studies have shown that obesity is associated with an increased risk of thyroid cancer. Leptin, an adipocyte-derived cytokine, can act as a growth factor on certain normal and transformed cells. Aberrant expression of leptin or leptin receptor has been detected in some types of cancer. The aim of this study is to determine immunohistochemical expression of leptin and leptin receptor in papillary thyroid cancer to investigate the relationship between their expression and clinicopathologic features. METHODS: The expression of leptin and leptin receptor was assessed in 49 primary neoplasms and 15 lymph node metastases using a semiquantitative immunohistochemical staining method. RESULTS: Leptin and leptin receptor were expressed in 37% and 51% of papillary thyroid cancer, respectively. They were not expressed in normal follicles. In the primary neoplasms and the metastatic nodes, expression of leptin correlated closely with leptin receptor (P < .001 for the primary neoplasms and P = .017 for nodal metastases). expression of either protein was associated with greater neoplasm size (leptin expression, 32.0 +/- 10.7 vs 20.5 +/- 8.4 mm; P = .001; leptin receptor expression, 27.9 +/- 11.5 vs 21.4 +/- 9.0 mm; P = .032). Coexpression of leptin and leptin receptor in primary neoplasms had greater incidence of lymph node metastasis (P = .038). CONCLUSION: expression of leptin and/or leptin receptor in papillary thyroid cancer is associated with neoplasm aggressiveness, including tumor size and lymph node metastasis.