Clinical Trial: Tissue Microarrays (TMAs) Construction in Lung Cancer Samples

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Evaluation of the Prognostic and Predictive Significance of EGFR, Kirsten Rat Sarcoma (KRAS), Anaplastic Lymphoma Kinase , Programmed Death-Ligand 1 (PD-L1) Protein and Microsatellite Instability (MSI

Brief Summary: Construction of a large cohort of lung cancer patients to evaluate the Prognostic and Predictive Significance of the molecular biomarkers Epidermal growth factor receptor (EGFR), KRAS, Anaplastic lymphoma kinase (EML4-ALK), Programmed Death-Ligand 1 (PD-L1) protein and Microsatellite Instability (MSI) in lung cancer: A tissue microarray-based study of 500 cases.

Detailed Summary:

Research hypothesis The research hypothesis for this study is that the expression/status of various molecular biomarkers (mainly including EGFR, KRAS, ALK, PD-L1 and MSI) may confer additional prognostic ( in terms of disease outcome i.e. PFS and OS) and/or predictive ( in terms of treatment response) information for lung cancer patients.

The research hypothesis is reflected in the primary objective of this study, which is to further evaluate the prognostic and predictive significance of currently existing molecular markers (EGFR, KRAS, ALK, PD-L1 and MSI), as well as of future biomarkers that may evolve. Secondary objectives include the evaluation of the differential expression/status of the examined biomarkers (EGFR, KRAS, ALK, PD-L1 and MSI) and standard clinicopathologic parameters including: PFS, OS and treatment response as well as age, gender, smoking history/status, performance status (PS), serum lactate dehydrogenase (LDH) and albumin levels, disease stage, tumor size, histology and grade, presence or absence of brain metastases, presence or absence of liver metastases and number of metastatic sites (all at diagnosis), and treatment data (type of treatment(s) received and treatment response. Potential correlations/interactions between the examined biomarkers will also be explored.

Rationale for conducting this study Rationale for biomarker selection The primary aim of this study is to further clarify the differential expression/status and frequency of EGFR and KRAS mutations, ALK rearrangements, PD-L1 protein and MSI, as well as their association with various clinicopathologic parameters, including treatment response, progression-free survival (PFS) and overall survival (OS), in a large and heterogeneous cohort of patients with lung cancer (including both NSCLC and SCLC).

500 cases will be studied. Three TMAs in total of lung adenocarcinoma, non-adenocarcinoma and SCLC, respectively- will be constructed. IHC for PD-L1 will be performed using commercially available antibodies and automated procedure. The EGFR, KRAS, ALK and MSI status will be assessed using routine molecular assays and procedures, either on the original FFPE tissue blocks or the constructed TMAs. MSI status will be evaluated using PCR-based method in FFPE tissue blocks. If that is not possible the status will be evaluate using IHC for the mismatch repair genes (MMR) hMLH1 and hMSH2 proteins expression on the TMAs. Biomarker characterization will be done according to the method that it will be used. For PD-L1: positive versus negative, for EGFR: mutant versus wild-type, for KRAS: mutant versus wild-type, for ALK: positive for ALK rearrangement versus negative for ALK rearrangement and for MSI: MSI high, MSI low, MSI stable.