Focal expression of thymidine phosphorylase associates with CD31 positive lymphocytic aggregation and local neo-angiogenesis in non-small cell lung cancer.

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.

Comparative evaluation of angiogenesis assessment with anti-factor-VIII and anti-CD31 immunostaining in non-small cell lung cancer.

Anti-Factor VIII vessel immunostaining has been widely used in the detection of angiogenesis in non-small cell lung cancer and other tumors. Several new antibodies have shown a higher sensitivity, and anti-CD31 has recently been proposed to be the standard for microvessel study. In the present study, we comparatively evaluated the two antibodies in 134 cases of early operable non-small cell lung cancer. The F8/86 (anti-Factor VIII-associated antigen) and JC70 (anti-CD31) MoAbs were used in paraffin-embedded material. Eye appraisal of vascular grade (VG) and microvessel score (MS) was performed by three experienced pathologists. Different cutoff points were used for the analysis of VG and MS correlation with nodal involvement, overall survival, and thymidine phosphorylase expression. Intra- and interobserver variability was minimal for both antibodies. MS and VG were significantly correlated with each other. However, 54 and 22% of cases with high anti-CD31 VG or high MS, respectively, had low vascularization on anti-Factor VIII assessment. Anti-CD31 scoring was significantly associated with nodal involvement and overall survival for all cutoff points considered, which was not verified for anti-Factor VIII staining. VG was the most significant indicator of nodal involvement and survival for both antibodies. Tumors with high VG by anti-CD31 but low or medium VG by anti-Factor VIII behaved as tumors of high neoangiogenesis, defining a poor prognosis (P = 0.005) despite the failure of anti-factor VIII antibody to highlight intense neoangiogenesis. Anti-CD31 MS significantly associated with thymidine phosphorylase overexpression (P = 0.01), whereas no correlation was found for anti-Factor VIII counting. It was concluded that anti-CD31 microvessel immunostaining has several advantages over anti-Factor VIII, being a more sensitive method for highlighting small, immature microvessels or single endothelial cells. This could be of importance in revealing possible correlation of tumor angiogenesis with metastatic behavior, prognosis, or angiogenic factor overexpression. Vascular grading was the best method for neovascularization assessment, efficiently defining groups of tumors with aggressive clinical course.