Heterogeneity of tumor oxygenation: relationship to tumor necrosis, tumor size, and metastasis.

ABSTRACT

PURPOSE: Measurements of oxygenation in the transplanted rodent KHT-C and SCC-VII tumors demonstrate significant heterogeneity from tumor to tumor as is observed in human tumors. This finding suggests that heterogeneity in oxygenation between tumors is likely related to factors associated with tumor growth rather than to intrinsic genetic differences. In this study we examined whether measurements of the oxygenation of individual KHT-C tumors were related to necrosis in the tumors or to tumor size and whether the more hypoxic tumors gave rise to more metastases. METHODS: Tumors were grown in the gastrocnemius muscle of C3H mice and tumor oxygenation was measured at defined sizes (approx. 0.35 g, 1.0 g, and 2.0 g) using an Eppendorf polarographic oxygen probe. Necrosis was assessed by examining histological sections cut from tumors used for the oxygen measurements. Metastasis was assessed by counting macroscopic lung nodules in mice sacrificed when their tumors reached a size of approximately 2 g. RESULTS: Tumor oxygenation in individual KHT-C tumors became poorer and necrosis became more extensive as the tumors grew larger but, at a size of 0.3-0.4 g, there was no relationship between oxygenation and extent of necrosis. In general, measurements of tumor pO2 at a size of 0.3-0.4 g were predictive of tumor PO2 in the same tumor at a size of about 1 g, but by the time the tumors reached a size of about 2 g they were all very hypoxic. There was a trend suggesting a relationship between macroscopic metastases in the lung and degree of hypoxia in the KHT-C tumors but this was not statistically significant. CONCLUSION: The results indicate that the heterogeneity of oxygenation seen in KHT-C tumors is not explained by different degrees of necrosis in the individual tumors. The lack of a correlation between increased metastasis formation and increased levels of hypoxia in the KHT-C tumors is not consistent with results reported for human tumors.