Localization of epidermal growth factor receptor-mutations using PNA:DNA probes in clinical specimens from patients with non-small cell lung cancer

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Abstract
Quickly identifying driver gene mutations in solid cancers is important. However, next-generation sequencing (NGS)-based mutation detection methods are time-consuming and expensive. Peptide nucleic acid (PNA) probe-based mutant mRNA detection systems are quick and inexpensive. We previously demonstrated that epidermal growth factor receptor (EGFR)-mutations were efficiently visualized in formalin-fixed paraffin-embedded (FFPE) specimens from transplanted non-small cell lung cancer (NSCLC) tumors using an EGFR mutation-specific PNA:DNA probe. Herein, the efficiency of PNA:DNA probes in detecting EGFR-mutations in FFPE specimens from patients with NSCLC and the colocalization of EGFR-mutations with tumor-infiltrating lymphocyte (TIL) status were determined. The EGFR mutation L858R-specific PNA:DNA probe detected heterogeneously localized mutations with a sensitivity similar to detection with the anti-L858R antibody. TIL analysis of L858R-mutated tumors revealed that CD8+PD-1+ T cells and CD68+ macrophages were scarce in tumors, but in the cytokeratin-positive intra-tumoral regions, CD4+, FoxP3+, and CD204+ cells tended to be more abundant in the L858R-positive tumor area than in the negative area. Thus, PNA:DNA probes specific for EGFR-mutations can detect areas with heterogeneous EGFR mutants in whole cancer tissues and can be used to evaluate the mutation-associated TIL status in EGFR-mutant cancer tissues.

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