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Hypoxic Cervical Cancers with Low Apoptotic Index Are Highly Aggressive¹

Department of Obstetrics and Gynecology, University of Leipzig, D-04103 Leipzig [M. H.], and Institute of Physiology and Pathophysiology, University of Mainz, D-55099 Mainz [K. S., S. H., P. V.], Germany

There is evidence from experimental work that hypoxia induces apo-ptosis in apoptosis-sensitive neoplastic cells and that this apoptotic sensitivity is lost during malignant progression. Oxygenation profiles and apoptotic indices in human squamous cell cancer of the uterine cervix have been determined, and a subgroup of tumors has been identified with low apoptotic index despite pronounced hypoxia representing carcinomas that consist of neoplastic cells with diminished apoptotic potential. These hypoxic low-apoptotic tumors show a high probability for lymphatic spread and for recurrence despite adjuvant treatment with radiation or chemotherapy in addition to radical surgery. The clinical results presented strongly support the hypothesis derived from experimental studies that the selection of apoptosis-insensitive neoplastic cell phenotypes in a hypoxic microenvironment is an important mechanism for malignant progression in solid tumors.

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