DIFFERENT PATTERNS OF STROMAL AND CANCER CELL THYMIDINE PHOSPHORYLASEREACTIVITY IN NON-SMALL-CELL LUNG-CANCER - IMPACT ON TUMOR NEOANGIOGENESIS AND SURVIVAL

Angiogenesis is recognized as an important step in tumour pathogenesis that is related to invasion and metastatic spread and which consequen tly results in poor clinical outcome. In this study, we have examined the role of tumour stroma-activated fibroblasts and macrophage infiltr ation in the development of the angiogenic and metastatic phenotype in non-small-cell lung cancer (NSCLC). A total of 141 cases of early sta ge I-Il NSCLC treated with surgery alone were analysed. The JC-70 (ant i-CD31) MAb was used for the assessment of vascular grade. The P-GF.44 C MAb was used to assess thymidine phosphorylase (TP) reactivity in ca ncer cells, stromal fibroblasts and macrophages, Cancer cell TP overex pression related to high vascular grade and to advanced T stage (P = 0 .0004 and P = 0.02). Expression of TP in stromal fibroblasts also corr elated with high angiogenesis (P = 0.01), but was independent of cance r cell expression. Fibroblast TP overexpression was related to abundan t stroma (P=0.003), suggesting that TP may be a marker of active strom a, Moreover, intense macrophage infiltration was associated with fibro blast TP reactivity, regardless of the amount of stroma, suggesting th at macrophages may be a major contributor to TP expression in stroma. Survival analysis showed that cancer cell TP overexpression was relate d to poor prognosis (P = 0.005). Although stroma TP is related to angi ogenesis, in the low vascular grade group it defined a group of patien ts with better prognosis (P = 0.02). It may be that fibroblast TP reac tivity is an indirect marker of tumour infiltration by functional macr ophages, which have an anti-tumour effect, We conclude that stromal ma crophage and fibroblast TP reactivity may have an important role in no n-small-cell lung cancer behaviour. Understanding the role of stromal fibroblasts and inflammatory cells and their interaction with oncoprot ein expression is essential for the elucidation of lung cancer pathoge nesis.