Evaluation of the Prognostic Role of a Panel of Biomarkers in Stage IB-IIIA Non-small Cell Lung Cancer Patients

Abstract

Background: Non-small cell lung cancer (NSCLC) remains a highly lethal disease worldwide and research for more effective treatment strategies is ongoing. Identification of molecular prognostic and predictive markers remains under investigation with results that are often conflicting. Patients and Methods: Seventy-three patients (n=73) with stage IB-IIIA completely resected NSCLC who were postoperatively treated with 6 cycles of paclitaxel and carboplatin from July 1998 to September 2002 took part in this study. Most stage IIIA patients subsequently received adjuvant radiotherapy. Cyclooxygenase-2 (COX-2), vascular endorhelial growth factor (VEGF), dihydrodiol dehydrogenase (DDH), receptor-binding cancer antigen expressed on SiSo cells (RCAS-1) and epidermic rrowth factor receptor (EGFR/HER-1) expression were assessed immunohistochemically; Heregulin family (HER1-4), VEGF and p53 were analysed by RT-PCR. Results: Totally, 61 (84%) men and 12 (16%) women with median age of 63 years and median PS of 0 were included in the study. There were 18 stage IB, 29 stage II and 26 stage IIIA patients. Sixty-seven samples were available for immunohistohemistry. COX-2 expression was detected in 24 patients (36%), VEGF in 14 (21%), RCAS1 in 31 (46%), DDH in 15 (22%). For EGFR, only 58 samples were evaluated, 13 of which were positive (22%). Messenger RNA expression data was only available for 60 patients; VEGF was detected in 32 (53%), p53 in 30 (50%), EGFR in 35 (58%), HER2 in 4 (7%) and HER3 in 19 (32%). HER4 was not detected in any sample. In the Cox analysis for overall survival (OS) and disease-free survival (DFS), none of the factors evaluated by IHC or RT-PCR reached statistical significance. Conclusion: Even though the biomarkers tested are expressed in a significant proportion of lung tumors, none of them was found to be of prognostic significance in patients with NSCLC.