MTE20.02 Molecular Testing in Small Samples

Abstract

Molecular targeted therapies have become a standard treatment for patients with lung cancer. Driver genetic alterations such as EGFR mutations, ALK rearrangements and ROS1 rearrangements are currently used as predictive biomarkers for EGFR tyrosine kinase inhibitors (TKIs), ALK inhibitors, and ROS1 inhibitors, respectively. In addition, antibodies blocking the PD-1 ligand PD-L1 have shown prominent antitumor activities and durable clinical response. Molecular analyses of these predictive biomarkers in tumor tissue or cytology specimens are the first prerequisite laboratory tests for the clinical management of lung cancers. Despite the increasing number of targets to be tested, most patients harboring non-small cell lung carcinoma (NSCLC) presents with advanced stage at the time of diagnosis, so the amount of tissue that can be acquired is very small. Small biopsy and cytology samples obtained from a variety of methods are acceptable for molecular testing, including transbronchial lung biopsy, endobronchial ultrasound– guided transbronchial needle aspiration, bronchial brushing or washing, computed tomography–guided gun biopsy or needle aspiration, and pleural fluid sampling. The molecular testing results using cytology samples are highly concordant with those of the corresponding tissue samples, especially with more sensitive methods. Routinely prepared cytology samples such as alcohol-fixed smears or cell block samples are also suitable for mutation testing. As targetable genetic alterations are increasingly identified, individual genotyping or molecular test seemed to be relatively inefficient and expensive. Thus, next-generation sequencing (NGS) technology with DNA or RNA is reported to be useful method for multiplexed and deep targeted sequencing. In this situation, each pathology laboratory needs to make a strategic approach to use these small samples in considerations of the important priorities for the management of the patients. In this MET session, I will introduce our experience of strategic approach to obtain the most useful information while reducing the loss of tissue using a small amount of samples. 1. Li T, Kung HJ, Mack PC, Gandara DR. Genotyping and genomic profiling of non-small-cell lung cancer: implications for current and future therapies. J Clin Oncol 2013; 31: 1039-49. 2. Brahmer JR, Tykodi SS, Chow LQ et al. Safety and Activity of Anti-Pd-L1 Antibody in Patients with Advanced Cancer. N Engl J Med 2012; 366: 2455-2465. 3. Shim HS, Choi YL, Kim L, et al. Molecular testing of lung cancers J Pathol Trans Med 2017; 51: 242-254.. 4. Sun PL, Jin Y, Kim H, Lee CT, Jheon S, Chung JH. High concordance of EGFR mutation status between histologic and corresponding cytologic specimens of lung adenocarcinomas. Cancer Cytopathol 2013; 121: 311-9. . small samples, Lung neoplasms, molecular testing