Evaluation of the prognostic role of a panel of biomarkers in stage IB-IIIA non-small cell lung cancer patients.
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.


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 growth 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.


CONCLUSIONS
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.
Timotheadou
Eleni
E
Department of Medical Oncology, Papageorgiou General Hospital, Aristotle University of Thessaloniki School of Medicine, Greece. nellitim@hotmail.com
Skarlos
Dimosthenis-Vasilios
DV
Samantas
Epaminondas
E
Papadopoulos
Savvas
S
Murray
Sam
S
Skrickova
Jana
J
Christodoulou
Christos
C
Papakostantinou
Christos
C
Pectasides
Dimitrios
D
Papakostas
Pavlos
P
Kaplanova
Jana
J
Vrettou
Eleni
E
Karina
Maria
M
Kosmidis
Paraskevas
P
Fountzilas
George
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D016190:Carboplatin; D017239:Paclitaxel