Programmed Death Ligand-1 Testing in Adenocarcinoma Lung: A Comparative Study of Cell Block versus Biopsy.

Background: Immunotherapy currently stands as a novel treatment option, specifically in cases of advanced non-small cell lung carcinoma (NSCLC). Expression of programmed death ligand-1 (PD-L1) in tumor cells forms the mainstay for the use of anti-PD-L1 monoclonal antibodies in the treatment of NSCLC. Aims: The objectives of the study were to assess utility of cell blocks for testing of PD-L1 in adenocarcinoma lung and to compare the expression of PD-L1 in cell blocks and the corresponding biopsy specimens. Materials and Methods: The current study was a prospective case series that included 20 cases of NSCLC-adenocarcinoma lung. Cases included in the study had biopsies performed from lung masses, along with which cell blocks were prepared from fine needle aspiration cytology (FNAC) samples. Testing for PD-L1 was done using the monoclonal PD-L1 antibody, SP-263 clone on the Ventana Benchmark XT system. PD-L1 expression was assessed only in the tumor cells, and cases with >1% expression, cytoplasmic or membranous, in tumor cells were categorized as positive. Results: PD-L1 expression was identified in the biopsy samples of tumor cells of 20% of cases (n = 4/20). In the corresponding cell blocks, PD-L1 expression was identified in the tumor cells of 15% of cases (n = 3/20). Sensitivity and specificity of cell blocks were 75% and 100%, respectively. Positive and negative predictive values were 100% and 94.12%, respectively. Conclusion: PD-L1 testing has both predictive and prognostic implications. PD-L1 testing in cell block samples is a potential alternative, specifically in cases where biopsy tissue is minimal or unavailable.

Epidermal growth factor receptor mutations in adenocarcinoma lung: Comparison of techniques for mutation detection.

Background: Targeted therapy using tyrosine kinase inhibitors in cases of non-small-cell lung carcinoma (NSCLC) that harbor epidermal growth factor receptor (EGFR) mutations has drastically improved the overall survival rate. The current study estimated the frequency of EGFR mutations in the Indian population by analyzing the diagnostic parameters of various techniques available for the detection of these mutations. Materials and Methods: A case series of 100 histologically diagnosed and immunohistochemically confirmed NSCLC with the adenocarcinoma phenotype comprises the study sample. EGFR mutations were detected using clone-specific immunohistochemistry (IHC), real-time polymerase chain reaction (PCR), and Sanger sequencing. Results: EGFR mutations were identified in 48% cases with 72.78% mutations involving exon 19. Clone-specific IHC had a low sensitivity of 46.43%, and the specificity was 79.17%. Sanger sequencing yielded interpretable results in 16% cases only, which were in concordance with the results of real-time PCR. Conclusion: EGFR mutations are increasingly being explored for targeted therapy and personalized medicine. Real-time PCR was found to be the best and the most accurate method for the detection of somatic EGFR mutations in adenocarcinoma primarily in the lungs.

ROS-1 re-arrangements and c-MET amplifications in adenocarcinoma lung: A tertiary care center study from North India.

BACKGROUND: C-ros oncogene 1, receptor tyrosine kinase (ROS 1) proto-oncogene 1, receptor tyrosine kinase (ROS-1) fusions are potent oncogenic drivers and these re-arrangements promote signal transduction programs leading to uninhibited cell survival and proliferation identified in 1-2% of cases of nonsmall-cell lung cancer. Mesenchymal epithelial transition factor (MET) receptor tyrosine kinase and its ligand are predominantly involved in epithelial mesenchymal transition and tissue regeneration. The MET amplification and overexpression is oncogenic in 3-7% cases. The objectives of this study were to identify the frequency of ROS-1 and c-MET protein expression in adenocarcinoma lung and to correlate it with the clinicopathological parameters and to analyze the histomorphology of cases that harbor the characteristic mutations (c-MET and ROS-1). MATERIALS AND METHODS: Study group comprised a prospective cases series of 90 cases of adenocarcinoma lung. ROS-1 protein expression was determined by immunohistochemistry using the D4D6 rabbit monoclonal antibody (Cell Signaling, Danvers, MA) and c-MET protein expressed was analyzed using the SP-44 clone (Ventana Medical Systems). RESULTS: c-MET protein expression was identified in 33.33% cases (n = 30/90) with statistically significant thyroid transcription factor-1 (TTF-1) positivity. ROS-1 protein expression was detected in 3.33% cases (n-3/90), in biopsies from the respiratory tree with TTF-1 expression. CONCLUSION: This is the first study from the Indian subcontinent to identify the frequency of ROS-1 re-arrangements and MET amplification in the Indian population. The availability of targeted therapy that has a significant impact on survival makes it essential to detect these less frequent mutations.