Genotyping and cytomorphological subtyping of lung adenocarcinoma based on liquid-based cytology

Liquid-based cytology (LBC) samples allow immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and molecular testing of nucleic acids to be performed in the remaining fixed cells. The current study aimed to examine the relationship between gene mutational status and cytomorphological features in primary lung adenocarcinoma (ADC) using LBC materials.

Forty consecutive patients with primary lung ADC underwent surgical resection in our hospital. Cytological material was obtained by scraping the cut-surface of the lesion, and samples were fixed and stored as LBC materials using CytoRich Red. Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma kinase (ALK), and c-ros oncogene 1 (ROS1) gene rearrangements were detected, and cytomorphological studies were performed.

Twenty cases (50%) were positive for EGFR mutation and four (10%) were positive for KRAS mutation. ALK gene rearrangement was identified in one case (2.5%) by IHC and FISH, and ROS1 gene rearrangement was identified in one case (2.5%) by IHC and real-time polymerase chain reaction. The KRAS-positive group included higher proportions of cases with an inflammatory background (100%), predominantly papillary architecture (75%), and papillary-type ADC pattern (75%) compared with the EGFR-positive group and the other group, which included ALK and ROS1 gene rearrangements.

LBC material is suitable for use in molecular testing. Differences in major gene aberrations detected by this method might predict specific cytomorphological features.