Association of tumor PDGFR-α and PDGFR-β expression and survival after resection of hepatocellular carcinoma.

Abstract

220 Background: Hepatocellular carcinoma (HCC) proliferates through angiogenic pathways mediated, in part, by vascular endothelial growth factor receptor 2 (VEGFR2) and platelet-derived growth factor receptors (PDGFR) α and β. We hypothesized that overexpression of these proteins is associated with decreased survival after resection. Methods: 57 patients with available tissue for analysis who underwent liver resection for HCC between 8/00 and 3/08 at one institution were identified from a prospectively maintained database. Tumors were assessed by immunohistochemistry for VEGFR2, PDGFR-α, and PDGFR-β expression and were graded by a single pathologist. Primary outcome was overall survival (OS). Results: Median age was 64 yrs; 65% were male. Median F/U was 25 mo, and OS was 26 mo. Median tumor size and number were 7 cm and 1, respectively. Macro- and microvascular invasion were present in 9% and 42% of patients, respectively. 25% had tumors that met Milan criteria. 9% had positive resection margins. 35% of patients had cirrhosis and the median nonadjusted MELD score was 7.5. Tumors exhibited differential expression of VEGFR2 (low: 79%, high: 21%), PDGFR-α (low: 93%, high: 7%), and PDGFR-β (low: 96%, high: 4%). After excluding all 30-day deaths (n=7), high PDGFR-α and β expression were independently associated with decreased OS (8.7 vs 29.1 mo, p=0.01; 2.8 vs 28.8 mo, p<0.001; respectively). When adjusted for tumor burden, margin status, and MELD score on independent multivariate analyses, both PDGFR-α and β expression were predictive of decreased survival (Table). Conclusions: High PDGFR-α and PDGFR-β expression are independently associated with decreased overall survival after resection of HCC. This finding may help to select patients who would benefit from targeted inhibitor therapy in the adjuvant setting. [Table: see text] No significant financial relationships to disclose.