[Molecular cytology: Opportunities and challenges]

Area of Science:

• Oncology
• Molecular Diagnostics
• Cancer Research

Context:

• Predictive marker analysis in non-small cell lung cancer (NSCLC) is challenging due to anatomical constraints and small biopsy sizes.
• Formalin-fixed paraffin-embedded (FFPE) tissue samples require stringent quality control and standardized procedures for reliable analysis.
• Cytological samples present an alternative with inherent advantages for molecular testing.

Purpose:

• To highlight the utility of cytological samples as an optimal starting material for predictive marker analysis in NSCLC.
• To explore the benefits of cytological specimens for advanced genomic assays and cell culture model generation.
• To demonstrate how cytological analysis can inform therapeutic decisions through comprehensive molecular profiling.

Summary:

• Cytological samples are ideal for predictive marker analysis, including fluorescence in situ hybridization and next-generation sequencing, overcoming limitations of traditional tissue biopsies.
• Rapid on-site evaluation (ROSE) allows for quick assessment of sample representativeness.
• Fresh cellular material from smears and fluids can be used to create 2D and 3D cell culture models for functional genomic assays, assessing multiple variants and identifying novel therapeutic vulnerabilities.

Impact:

• Enables more comprehensive molecular profiling of tumors, particularly in challenging cases like NSCLC.
• Facilitates the application of advanced functional genomic assays alongside conventional biomarker testing.
• Provides crucial information for therapy decision-making in molecular tumor boards, potentially uncovering new treatment strategies.