Focal expression of thymidine phosphorylase associates with CD31 positive lymphocytic aggregation and local neo-angiogenesis in non-small cell lung cancer.
Giatromanolaki A., Koukourakis MI., Kakolyris S., Kaklamanis L., Barbatis K., O'Byrne KJ., Theodosssiou D., Harris AL., Gatter KC.
Platelet-derived endothelial cell growth factor (PDECGF) also called thymidine phosphorylaze (TP) has been shown to have considerable angiogenic activity. 141 cases of early stage non-small cell lung cancer were stained for TP and vascular grade using the P-GF.44C and JC70 MoAbs, respectively. The early steps of TP activation could be identified in 27 cases, where one or two foci of cancer cell TP overexpression occurred within a general pattern of negative/weak staining. Thirty-three foci of overexpression were analyzed for the local microvessel density in the adjacent stroma, assessed by microvessel counting (MC) and Chalkley Score (CS) comparatively with the remaining TP negative tumor areas. The degree of local inflammatory (lymphocyte and macrophage) infiltration was also assessed. A statistically significant increase of mean MC and mean CS was observed in areas of TP overexpression in both low and high angiogenesis cases. Overall, the mean MC in overexpressing areas, assessed in 250x fields, was 20.4 +/- 12.8 vs. 13.6 +/- 9.5 in areas with no TP expression (p = 0.0001). The mean CS was 5.7 +/- 3.3 and 4.0 +/- 2.1, respectively (p = 0.0003). Ten out of 19 (54%) cases with low lymphocytic infiltration showed marked stromal lymphocytic infiltration in the area of focal TP overexpression (p = 0.01). The present study provides further evidence of a direct association of TP and the process of angiogenesis in non-small cell lung cancer.