Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Accurate differentiation between adenoca Show more
Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Accurate differentiation between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is critical for informing personalized therapies. Thyroid transcription factor-1 (TTF-1) and p40 are traditionally regarded as mutually exclusive markers of ADC and SCC, respectively. However, a subset of tumors exhibits co-expression of TTF-1 and p40, presenting diagnostic challenges and suggesting underlying biological distinctiveness. This study aimed to characterize the clinicopathological, molecular, and immunohistochemical features of NSCLCs co-expressing TTF-1 and p40, in order to clarify their biological and clinical significance. A retrospective analysis was performed on NSCLC cases diagnosed at the Central Clinical Hospital of the Medical University of Łódź between May 2021 and November 2022. Clinicopathological and survival data were collected. Tumors co-expressing TTF-1 and p40 underwent immunohistochemical evaluation and RNA/DNA-based next-generation sequencing (NGS). Of 94 NSCLC cases analyzed, 18 (19.1%) demonstrated co-expression of TTF-1 and p40. These tumors were significantly more likely to exhibit solid growth patterns compared to control cases (P=0.03), but no significant difference in overall survival (OS) was observed (P=0.46). Among 17 samples subjected to NGS, genetic alterations were identified in 15 (88.2%) cases, with NSCLCs co-expressing TTF-1 and p40 appear to represent a biologically distinct and poorly differentiated subgroup, frequently associated with Show less