Molecular pathology of lung cancer: current standards and further developments

Lung cancer is a prime example of the success of molecular diagnostics direct targeted and immunotherapies in solid tumors. However, optimal therapy stratification for the patient requires comprehensive molecular diagnostics. Very different, sometimes complex biomarkers have to be tested on generally limited diagnostic material with high sensitivity and thus present molecular pathology with new challenges. The array of different analyses that are needed range from simple mutation analyses to copy number variations, translocations as well as tumor mutational burden estimation (TMB). Already now pathologists are required to integrate these findings into a single instructive report that in the future will need to include not only positive predictive findings but also marks indicative of lack of response to a particular therapy. This will be largely done via next generation sequencing (NGS) panels, which can simultaneously identify all therapy-relevant gene alterations (single nucleotide variants, SNV; copy number variations, CNV; translocations or TMB). The goal is to identify patients who are highly likely to respond to targeted or immunotherapy due to a specific tumor type. It will also be important to identify patients who have negative predictive tumor markers. The authors provide an overview of currently established biomarkers and those close to implementation in routine diagnostics.