Expression of hypoxia-inducible factor 1alpha and cathepsin D in pituitary adenomas.
Hypoxia-inducible factor (HIF)-1alpha is a crucial transcription factor involved in the adaptive response to hypoxia, whereas cathepsin D, which regulates angiostatin in several cancer cell lines, has been reported to be upregulated by HIF-1alpha. In order to determine the involvement of angiogenesis in pituitary adenomas, we studied the expression of both HIF-1alpha and cathepsin D in tissues from 58 patients (39 women, 19 men, ranging in age from 20 to 78 yr), sorted by histological group, and assayed by double immunohistochemistry. HIF-1alpha immunoreactivity, confined to the nucleoplasm, was present in both tumor and vascular endothelial cells. There was no difference in microvascular density (p = 0.7761) by histotype. ACTH-producing adenomas showed the lowest level of HIF-1alpha, whereas prolactin (PRL)-producing adenomas and HIF-1alpha-positive microvessels showed the highest (p < 0.001). In contrast, the lowest expression of cathepsin D was observed in PRL-producing adenomas, whereas the highest expression was detected in ACTH-producing adenomas (p < 0.0001). Imaging analysis with fluorescence double immunohistochemistry showed that HIF-1alpha-negative tumor cells did not express significantly higher levels of cathepsin D. In these poorly vascularized tumors, the hypoxic marker HIF-1alpha may not downregulate cathepsin D. The mechanisms of tumor angiogenesis and cell invasion in pituitary adenomas may differ from those in other tumor cells.
Yoshida
Daizo
D
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan. dyoshida@nms.ac.jp
Kim
Kyongsong
K
Yamazaki
Michio
M
Teramoto
Akira
A
D000236:Adenoma / Q000098:blood supply / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002402:Cathepsin D / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000098:blood supply / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D002402:Cathepsin D