Expression pattern of leptin and leptin receptor (OB-R) in human gastric cancer.
OBJECTIVE
To examine the expression of leptin and its receptor, OB-R, in normal gastric mucosa and neoplasia.


METHODS
By immunohistochemical staining using specific antibodies, we evaluated the expression of leptin and OB-R in 207 gastric carcinomas (100 early and 107 advanced carcinomas) and analyzed their relationship with clinicopathological features.


RESULTS
Both normal gastric epithelium and carcinoma cells expressed a significant level of leptin. In cases with OB-R staining, carcinoma cells showed OB-R-positive expression, but the intensity was weaker than that in normal mucosa. The expression of OB-R showed a significant correlation with the level of leptin expression. The expression levels of both leptin and OB-R tended to increase as the depth of tumor invasion or TMN stage increased (P < 0.01). Lymph node metastasis was detected in 49.5% (47/95) of leptin-strong cases and in 50.5% (48/95) of OB-R-positive cases, and the rate was 33% (37/112) in leptin-weak cases and 17% (19/112) in OB-R-negative cases. Both venous and lymphatic invasion also tended to be observed frequently in positive tumors as compared with negative tumors. Interestingly, in the 96 leptin- or OB-R-positive tumors, hematogenous metastasis was detected preoperatively in 3 (3.1%) patients. In contrast, none of the carcinomas that lacked expression of leptin and OB-R showed hematogenous metastasis.


CONCLUSIONS
Overexpression of leptin and expression of OB-R may play a positive role in the process of progression in gastric cancer. Functional upregulation of leptin/OB-R may have a positive role in the development and initial phase of progression in gastric cancer.
Ishikawa
Makoto
M
Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. makoto-ishi@umin.ac.jp
Kitayama
Joji
J
Nagawa
Hirokazu
H
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D054411:Receptors, Leptin; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology
C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin