Correlative Study of Tumor Hypoxia and Metastatic Potential in Breast Cancer
Annual rept. 1 Sep 1998-31 Aug 1999
NORTH CAROLINA UNIV AT CHAPEL HILL
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Human tumor hypoxia is associated with poor prognosis independent of treatment modality. In addition to radioresistance, hypoxia induced stress factors may lead to malignant progression. Using a novel physiological approach to detect tumor hypoxia with pimonidazole in human breast tumors, the aims are to study relationships between hypoxia and biomolecular markers of cell proliferation PCNA, angiogenesis MVD-microvessel density, VEGF, p53, apoptosis, and regional nodes as clinical indicator of metastases. Breast cancer patients enrolled in an IRB approved study receive pimonidazole intravenous infusion. Breast tumor biopsy specimens are examined with immunohistochemical techniques for pimonidazole binding hypoxia and for the above biomolecular markers. Regional node metastases data are recorded. Twelve patients have been enrolled on the study. Tumor hypoxia detected with pimonidazole binding ranges from 0-33 in the tumor biopsies examined to date. MVD ranges from 2-82 vessels per field. Other studies are awaiting additional patient enrollment. There are no adverse reactions to the pimonidazole infusion Appendix I-III. This is the first demonstration of tumor hypoxia detection in human breast cancer using pimonidazole. These data suggest it will be a valuable technique for correlative studies of tumor hypoxia with both clinical and biomolecular markers of tumor aggressiveness.
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