Frequency of expression and prognostic implications of emerging molecular targets in pulmonary squamous cell carcinoma

ABSTRACT Background: NSCLC-Squamous cell carcinoma (SCC) is characterized by poor survival largely due no definitive markers for targeted therapy. KRAS (Kirsten rat sarcoma viral oncogene homolog) is a proto-oncogene associated with resistance standard chemotherapy regimens. Discoidin domain receptor 2 (DDR2), fibroblast growth factor receptor-1(FGFR-1) and mesenchymal epithelial transition (MET) are receptor tyrosine kinases that regulate proliferation, apoptosis and invasion. Aims: The objectives were to assess frequency of FGFR1, DDR2,c-MET protein over-expression and KRAS mutations in NSCLC-SCC and to co-relate expression of molecular markers with clinico-pathological parameters. Materials and Methods: The study was a retrospective and prospective case series of 150 cases of NSCLC-SCC. Testing for KRAS, DDR-2, cMET and FGFR1 was done using immunohistochemistry (IHC). KRAS IHC was validated using real time polymerase chain reaction testing. Results: Molecular marker expression was identified in 37.33% (n=56/150) cases, among which 80.35% (n=45/56) cases had a single mutation and 19.64% cases(n=11/56) had multiple mutations. FGFR-1 protein over-expression was identified in 8% cases and cMET protein over-expression in 4.67% cases. DDR-2 over-expression was present in 19.33% cases and KRAS protein over-expression in 14.67% cases. Co-expression of DDR-2 and KRAS was identified in 72.72% cases. DDR2 protein over-expression is identified in smokers and cases with distant metastasis. KRAS protein over-expression was more frequent in cases >40 years of age with advanced disease stage. Conclusions: The targets evaluated have potential drugs currently under trial phase. This may help to define the subgroup for use of targeted therapy in NSCLC-SCC and in designing new treatment protocols.