We evaluated the levels and distribution of
hypoxia in 31 human
tumors using fluorescent immunohistochemical detection of binding by the
2-nitroimidazole, EF5.
Hypoxia was found to be a heterogeneous property of human
tumors.
Necrosis was usually found adjacent to the highest level of binding in an individual patient's
tumor. However,
hypoxia often occurred without
necrosis. In the group of
tumors studied, the most common relationship between blood vessels (PECAM/CD31) and EF5 staining was consistent with diffusion-limited
hypoxia; acute
hypoxia occurred infrequently. Within a given patient's
tumor, there was an inverse correlation between regions of proliferation (Ki-67) and regions of
hypoxia. Again, however, when these parameters were examined in a group of patients, the absence of proliferation did not predict the presence of
hypoxia. The relationships between
hypoxia and other
biologic endpoints are complex, but, within a given
tumor's spatial relationships, they are in accord with known physiologic principles. Thus, our data emphasize that the relationships between
hypoxia and other
biologic parameters vary between patients.
Necrosis, proliferation, and blood vessel distribution cannot predict the level or presence of
hypoxia in an individual patient's
tumor.