Expression of hypoxia-inducible factor 1alpha in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy.
OBJECTIVE
To investigate the impact of expression of hypoxia-inducible factor (HIF)-1alpha on prognosis and on response to chemotherapy in epithelial ovarian tumors.


METHODS
Expression of HIF-1alpha protein was studied by immunohistochemistry in 102 specimens of epithelial ovarian cancers, in 50 borderline tumors, and in 20 cystadenomas. Results were correlated with p53, p21, and bcl-2 expression, microvessel density (MVD), apoptotic rate of tumor cells, and survival.


RESULTS
In 68.6% of ovarian cancers and 88% of borderline tumors, expression of HIF-1alpha was observed. There was a significant correlation of HIF-1alpha protein expression and MVD (P < 0.001). HIF-1alpha overexpression alone and MVD showed no impact on survival of cancer patients. Furthermore, the response to platinum-based chemotherapy was independent from HIF-1alpha expression. Expression of HIF-1alpha correlated with apoptotic rate in the majority of cases, especially in low malignant potential tumors. In contrast, in cancer patients with strong expression of HIF-1alpha and p53 protein overexpression, not only a significantly increased MVD (P = 0.032, Mann-Whitney test) but also a significantly shorter overall survival was observed (P < 0.0001, Cox regression). The apoptotic rate was very low in these tumors.


CONCLUSIONS
HIF-1alpha protein overexpression alone has no impact on the prognosis of ovarian cancer. The combination of HIF-1alpha protein overexpression with nonfunctional p53, however, indicates a dismal prognosis.
Birner
P
P
Institute of Clinical Pathology, University of Vienna, A-1090 Vienna, Austria. peter.birner@akh-wien.ac.at
Schindl
M
M
Obermair
A
A
Breitenecker
G
G
Oberhuber
G
G
D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004848:Epithelium / Q000473:pathology*; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)