Ductal adenocarcinoma of the pancreas: Expression of growth factor receptors, oncogenes and suppressor genes, and their relationship to pathological features, staging and survival.

Abstract

Pancreatic ductal adenocarcinoma results in high short-term mortality despite recent advances in diagnostics, surgery and chemotherapy. Modern chemotherapeutic agents directed to specific tumor receptors have higher therapeutic efficacy and lower adverse effects. However, few studies exist that evaluate the clinical impact in pancreatic cancer. The expression of tumor growth factor receptors, oncogenes and tumor suppressor oncogenes in surgical pancreatic cancer specimens as related to pathological characteristics, staging and prognosis was evaluated. Data were recorded for 50 patients who underwent a pancreatic cancer resection and were suitable for immunohistochemical evaluation (32 male, mean age 61 years, range 44-78) with regard to pTN, tumor size and location, histological differentiation grade, vascular and perineural invasion, adjuvant chemotherapy and survival time. Tumor specimens and normal pancreatic tissue were deparaffinized and the expression of vascular epidermal growth factor (VEGF) receptors (R)-1 and -2, epidermal growth factor receptor (EGFR), Her-2/neu, COX-2, p16, p21 and p53 was immunohistochemically evaluated using tissue microarrays. Associations between molecular marker expression and clinicopathological tumor characteristics were evaluated using the Chi-square test (SPSS) and the survival time was defined. The Kaplan-Meier method was utilized to analyze survival curves, verified by the log-rank test. No molecular markers evaluated were expressed in normal tissue. Tumor expression data included VEGF-R1 (74%), EGFR (52%), Her-2/neu (7.84%), COX-2 (21.5%), p16 (29.4%), p21 (21.7%) and p53 (50%). Tumors expressing VEGF-R1, EGFR and/or p53 were larger (p<0.02), frequently poorly differentiated (p<0.05) and more frequently associated with perineural and lymph node invasion (p<0.05). Marker expression did not correlate with pathological tumor characteristics. The median post-surgery survival was 15 months; 60 and 27% patients survived to 12 and 24 months, respectively, with a longer survival time in patients receiving adjuvant chemotherapy (n=20) (median 36 vs. 15 months, p<0.02). Growth factor receptors, oncogenes and tumor suppressor genes were frequently expressed in pancreatic cancer tissue. VEGF-R1, EGFR and p53 expression were associated with poor tissue differentiation and perineural and lymph node infiltration. Only VEGF-R1 expression was associated with a longer survival time and a more favorable response to adjuvant chemotherapy.