Intratumoral heterogeneity for expression of tyrosine kinase growth factor receptors in human colon cancer surgical specimens and orthotopic tumors

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The design of targeted therapy, particularly patient-specific targeted therapy, requires knowledge of the presence and intratumoral distribution of tyrosine kinase receptors. To determine whether the expression of such receptors is constant or varies between and within individual colon cancer neoplasms, we examined the pattern of expression of the ligands epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-B (PDGF-B) and their respective receptors in human colon cancer surgical specimens and orthotopic human colon cancers growing in the cecal wall of nude mice. The expression of EGFR and VEGFR on tumor cells and stromal cells, including tumor-associated endothelial cells, was heterogeneous in surgical specimens and orthotopic tumors. In some tumors, the receptor was expressed on both tumor cells and stromal cells, and in other tumors, the receptor was expressed only on tumor cells or only on stromal cells. In contrast, PDGFR was expressed only on stromal cells, in both surgical specimens and orthotopic tumors. Examination of receptor expression in both individual surgical specimens and orthotopic tumors revealed that PDGFR was expressed only on stromal cells and that patterns of EGFR and VEGFR2 expression differed between tumor cells. This heterogeneity in receptor expression between different tumor cells suggests that only therapeutic regimens inhibiting multiple tyrosine kinase receptor pathways are likely to be effective against human colon carcinomas.