Biomarkers Testing in Malaysia? How to Choose.
Dr Roziana Ariffin, Pantai Premier Pathology Hospital Pantai Bangsar (Residential), Sunway Medical Center (Visiting)

It is important for patients with advanced NSCLC  to be offered  broad molecular panel that identifies all of the established actionable driver mutations which includes ALK, BRAF, EGFR, KRAS p.G12C, METex14 skipping, NTRK1/2/3, RET, ROS1) and PD-L1 expression. The best approach is by using either a single assay or a combination of a limited number of assays—and optimally also identifies emerging actionable molecular biomarkers, including high-level MET amplification and ERBB2 (HER2) mutations. The NCCN NSCLC Panel recommends molecular testing for less common EGFR mutations—EGFR S768I, L861Q, and G719X. It is important to remember two principles: (a) the fewer times paraffin embedded material (tissue or cytological as cell blocks) is placed in a microtome, the more will be spared; and (b) the order of biomarker prioritisation is important, as the tissue can be depleted . A Tiered testing approach, based on the low prevalence of cooccurring biomarkers, are acceptable and maybe more realistic especially in a limited resource economy like ours. Broad genomic profiling may also be used to assess for mechanisms of resistance in patients with disease progression on targeted therapy. This can also distinguish separate primary lung cancers from intrapulmonary metastases. Reporting variants can be classified based on their pathogenicity. PD-L1 expression by IHC should be part of algorithm. Regarding PDL1 testing; preanalytical conditions, the most critical step is an enough time of fixation (i.e. at least 6 h), but storage time could also be relevant (i.e. archival material fewer than 3 years is recommended). PD-L1 is expressed at the membrane level, while intracytoplasmic expression is less frequent (not considered a positive result) . Role of liquid biopsy in NSCLC will also be addressed.