Immunohistochemistry evaluation of biomarker expression in non-small cell lung cancer (Pharmacogenoscan study)

Abstract

Objectives: Platinum-based chemotherapy regimens are the standard treatment of non-small cell lung cancer (NSCLC). In this study, our objective was to identify tumor tissue protein biomarkers that might predict a benefit from these treatments.

Materials and methods: The Pharmacogenoscan study prospectively included consecutive chemotherapy-naive NSCLC patients at any stage between 2005 and 2010 at six hospitals in the Rhône-Alpes-Auvergne region of France. Of the 537 patients in the full analysis set, 460 had a complete histological diagnosis. We used the tumor tissue samples for an immunohistochemical evaluation of eight biomarkers: ERCC1, BRCA1, p53, p27kip1, class III β-tubulin (TUBB3), Bax, Fas, and FasL. We looked for associations between these biomarkers and the disease control rate (DCR) after 2/3 cycles of platinum-based chemotherapy, progression-free survival (PFS), and overall survival (OS).

Results: A tissue sample adequate for testing at least one biomarker was available for 289 patients. We found no significant association between biomarker expression levels and clinical or pathological variables; TUBB3 showed a trend toward higher expression in adenocarcinomas (P=0.005). For none of the biomarkers were significant associations found between expression level and DCR, PFS, or OS. TUBB3-negative and FasL-negative tumors showed associations of borderline significance with higher DCR.

Conclusion: In a large cohort of patients with predominantly advanced or metastatic NSCLC, none of eight tested immunohistochemical biomarkers predicted the chemotherapy response or survival. Our data indicate limited usefulness of protein biomarkers in metastatic NSCLC and a need for further research based on molecular signatures of greater complexity.

Keywords: BRCA1; CI; DCR; DNA; Disease control rate; Drug response biomarkers; ERCC1; Fas ligand; FasL; HES; IHC; IQR; Immunohistochemistry; Lung neoplasms; MIA; NER; NSCLC; OS; PFS; PS; Prognosis; Survival; TUBB3; breast cancer susceptibility gene 1; class III β-tubulin; confidence interval; deoxyribonucleic acid; disease control rate; enzyme repair cross-complementation group 1; hematoxylin–eosin–saffron; immunohistochemistry; interquartile range; microtubule-interfering agents; non-small cell lung cancer; nucleotide excision repair; overall survival; performance status; progression-free survival.