Expression of leptin, leptin receptor, and hypoxia-inducible factor 1 alpha in human endometrial cancer.
Recent studies suggested that Ob (Ob) and its receptor (ObR) could be involved in the pathogenesis of various human malignancies, among others in endometrial cancer. Moreover, hypoxia, which is associated with solid tumors, might stimulate, through hypoxia-inducible factor 1alpha (HIF-1alpha), expression of Ob and ObR. In this article, we analyzed by immunohistochemistry the expression of Ob, ObR, and HIF-1alpha in 60 cases of human endometrial cancer tissues as well as in 25 cases of normal endometria. Additionally, we assessed correlations among studied proteins as well as relationships with selected clinicopathological features of endometrial cancer. Immunoreactivity for Ob, ObR, and HIF-1alpha protein was observed in 56.7%, 30.0%, and 78.3% of endometrial cancers, respectively. The expression of HIF-1alpha showed a significant positive correlation with Ob (P < 0.0001, r = 0.573) and ObR (P = 0.020, r = 0.299). Moreover, we noted positive correlation between Ob and ObR (P = 0.001, r = 0.429). No statistically significant relationship was revealed between Ob, ObR, and HIF-1alpha protein in regard to patient's age, histological grade, and extent of tumor growth (pT). In conclusion, HIF-1alpha, which is related to tissue hypoxia in endometrial cancer, seems to be associated with overexpression of Ob and ObR. Ob could exert autocrine effect to stimulate endometrial cancer progression. Thus the autocrine Ob loop should be taken into consideration as a novel potential target in endometrial cancer prevention and treatment.
Koda
Mariusz
M
Department of General and Clinical Pathomorphology, Medical University of Bialystok, Waszyngtona St. 13, 15-269 Bialystok, Poland.
Sulkowska
Mariola
M
Wincewicz
Andrzej
A
Kanczuga-Koda
Luiza
L
Musiatowicz
Boguslaw
B
Szymanska
Magdalena
M
Sulkowski
Stanislaw
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019898:Autocrine Communication / Q000235:genetics; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis* / Q000235:genetics; D020738:Leptin / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D054411:Receptors, Leptin
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin