Association of DEK Gene Alterations with Prognosis and Immunotherapy Treatment in Advanced Squamous Cell Carcinoma of the Lung

Background: The DEK::AFF2 fusion has been recently described in sinonasal squamous cell carcinomas; however, its presence and clinical impact in pulmonary squamous cell carcinoma (SCC) remain unclear. This study aimed to investigate the frequency of DEK rearrangement and DEK::AFF2 fusion in advanced lung SCC and to evaluate their association with PD-L1 expression, prognosis, and response to immunotherapy. Methods: A total of 128 patients diagnosed with pulmonary SCC (2017–2023) were analyzed. DEK rearrangements were identified using fluorescence in situ hybridization (FISH), while DEK::AFF2 fusion transcripts were evaluated via RT-PCR. PD-L1 expression was assessed immunohistochemically using the SP263 clone. Statistical analyses included non-parametric tests, Kaplan–Meier survival analysis, and Cox regression. Results: DEK rearrangements were detected in 29 (21.8%) cases. DEK-positive tumors exhibited significantly lower PD-L1 expression (p = 0.010), while no independent prognostic impact on survival was observed (p > 0.05). DEK::AFF2 fusion was confirmed by RT-PCR in all DEK-rearranged tumors. Conclusions: DEK alterations are recurrent in advanced pulmonary SCC and inversely correlated with PD-L1 expression, suggesting a distinct molecular subgroup potentially resistant to immunotherapy.