Prognostic relevance of 3q amplification (AMP) in a racially diverse patient population with advanced squamous cell carcinoma of the lung

e15142 Background: Amplification (AMP) of 3q is the most common genetic alteration in squamous cell carcinoma of the lung (LUSC) with the most frequently amplified region being 3q26-3q28. It represents one of the most striking molecular differences between LUSC and adenocarcinoma. We identified a minimal common region (MCR) of AMP constituted by 25 genes within a large amplicon on chromosome 3q by analyzing data of 476 patients with LUSC from The Cancer Genome Atlas (TCGA) and extracting copy number alteration data from cBioPortal. Full 25-gene MCR AMP was detected in 46.4% of the cases and was associated with better disease-specific survival (NR vs 9.25 years, 95% CI [5.24-NR]; p = 0.011) and progression-free interval (8 vs 4.9 years, 95% [3.5-NR]; p = 0.020). The TCGA cohort was mainly comprised of Caucasians (69.7%) and patients with early-stage disease (98.7%). We conducted a retrospective pilot analysis to validate the prognostic value of MCR AMP using a racially diverse cohort with advanced LUSC. Methods: We retrieved tissue samples for 33 patients with stage III or stage IV LUSC and collected retrospective data from Electronic Medical Records. The pathologist reviewed the slides to ensure the adequacy of tumor tissue. MCR AMP was evaluated via laboratory- developed FISH probe spanning MCR region. FISH test that showed a cluster of signals with more than 4 copies was regarded as positive; we used a control probe for the 3p arm which is typically not amplified in LUSC. Results: The mean age of the cohort was 69.1 years, 57.6% were males, 39.4% were African Americans (AA) and 54.5% were Caucasians, 66.7% had stage 3, and 33.3% had stage 4. Only 6.1% were never smokers and 84.8% were former smokers. MCR AMP was detected in 54.5% (n = 18) of the cases. PD-L1 status was available for 21 (63%) cases, 6 cases (3 had MCR AMP) were PD-L1 negative (TPS < 1%), and 15 cases (9 had MCR AMP) were PD-L1 positive (TPS > 1%). Consistent with the results observed in the TCGA cohort, MCR amplified cases had a trend towards better overall survival (OS) compared to non-amplified cases (1.74 vs 0.91 years; HR = 0.57, 95% CI [0.26-1.24], p = 0.15) as well as a trend towards better progression-free survival (PFS) (0.90 vs 0.74 years; HR = 0.88, 95% CI [0.43-1.81], p = 0.73). Conclusions: This pilot analysis shows that MCR AMP carries a prognostic value in a racially diverse patient population with advanced LUSC, similar to our observations in the TCGA cohort. Further validation in a large cohort is in progress.