Evaluation of TTF-1, Napsin A, p40, and p63 in the Subtyping of Non–Small Cell Lung Carcinoma: A Cross-Sectional Study from India

Background & Objective: Subtyping non–small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is crucial for selecting appropriate molecular tests, as driver mutations are often subtype-specific. This study aimed to evaluate the utility of TTF-1, Napsin A, p40, and p63 immunohistochemical (IHC) markers in subtyping NSCLC on small biopsies, with the goal of identifying a minimal marker panel. Methods: This retrospective, cross-sectional study was conducted at Kasturba Medical College, Mangalore, from January 2014 to December 2020. All NSCLC cases diagnosed during the study period were included. Immunohistochemical expressions of TTF-1, Napsin A, p40, and p63 were evaluated and correlated with morphological findings. Results: Ninety-five NSCLC cases were included: adenocarcinoma (n = 35), squamous cell carcinoma (n = 57), and NSCLC-not otherwise specified (NOS) (n = 2). IHC reclassification based on marker expression resulted in six ADC cases retyped as SCC and eight SCC cases retyped as ADC. TTF-1 and Napsin A expression were significantly associated with adenocarcinoma (p < 0.001), while p40 and p63 expression were significantly associated with SCC (p < 0.001). Conclusion: IHC is essential in overcoming the diagnostic limitations of small biopsy specimens, especially in morphologically heterogeneous tumors. A minimal panel comprising TTF-1 and p40 is sufficient for accurate subtyping of NSCLC and can help preserve tissue for downstream molecular testing.