Differential prognostic impact of platelet-derived growth factor receptor expression in NSCLC

Preclinical evidence suggests that stromal expression of platelet-derived growth factor receptors (PDGFRs) stimulates tumor development and diminishes intratumoral drug uptake. In non-small cell lung cancer (NSCLC), the clinical relevance of stromal PDGFR expression remains uncertain. Tumor specimens from 553 patients with primary operable stage I-IIIB NSCLC was obtained and tissue microarrays (TMA) were constructed (Norwegian cohort). Immunohistochemistry (IHC) was used to evaluate the expression of PDGFR alpha and -beta in stromal cells and to explore their impact on patient survival. Results were validated in a non-related cohort consisting of TMAs of 367 stage I (A and B) NSCLC patients (Swedish cohort). High stromal PDGFR alpha expression was an independent predictor of increased survival in the overall populations and SCC (squamous cell carcinoma) subgroups of both investigated cohorts. PDGFR beta was an independent predictor of poor survival in the overall Norwegian cohort and an independent predictor of increased survival in the ADC (adenocarcinoma) subgroup of the Swedish cohort. Tumors displaying the combination PDGFR alpha-low/PDGFR beta-high exhibited inferior survival according to increasing stage in the Norwegian cohort. This study confirms that high stromal expression of PDGFR alpha is a predictor of increased survival in NSCLC. Further exploration of the prognostic impact of PDGFR beta and the relationship between PDGFRa and -beta is warranted.