Optimizing EGFR Mutation Testing in Resource-Limited Settings: A Comparative Analysis of Diagnostic Platforms in Libya
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Background
Lung cancer mortality is rising in Libya, but access to molecular diagnostics for EGFR mutations—essential for guiding tyrosine kinase inhibitor therapy—remains severely limited. Selecting an appropriate testing platform requires balancing analytical performance against cost and infrastructure constraints.
Methods
We conducted a prospective comparative validation study using formalin-fixed paraffin-embedded (FFPE) tissue samples from Libyan non-small cell lung cancer (NSCLC) patients. Following stringent DNA quality control, samples were tested in parallel across four platforms: multiplex real-time PCR (MRT-PCR), reverse hybridization strip assay (RHSA), agarose gel electrophoresis (AGE), and immunohistochemistry (IHC). Performance was assessed by inter-method concordance, turnaround time, and cost per test.
Results
Of 30 initial samples, only six (20%) met quality thresholds (A260/A280 1.70–1.90; concentration ≥10 ng/µL), highlighting pre-analytical challenges. Three samples harbored EGFR exon 19 deletions. A critical discordance was identified: one sample tested negative by MRT-PCR (Ct ≈38, ΔCt=13) but positive by RHSA, AGE, and IHC, indicating a false-negative result from the reference method. IHC and RHSA offered the most favorable balance of cost (USD 40–75/test) and operational feasibility, while MRT-PCR (USD 150/test) required specialized infrastructure.
Conclusions
Relying solely on automated PCR may lead to under-diagnosis in low-cellularity or degraded FFPE samples. We recommend a hybrid algorithm: IHC as a cost-effective primary screen, followed by RHSA for confirmation. This approach optimizes resource allocation and improves diagnostic equity in Libya.
