The Role of p40, p63, MAdL and TTF-1 in Differential Diagnosis of Primary Lung Adenocarcinoma, Squamous Cell Carcinoma and Metastatic Adenocarcinomas of The Lung

Objective: Lung cancer is the most common and fatal type of cancer in both women and men. Due to differences in treatment, it is important to accurately distinguish
between lung cancer subtypes. Algorithms recommend using maximum of two markers (ie, a single adenocarcinoma marker and a single squamous marker) in each
case to preserve tissue for molecular studies. This study aimed to determine the optimal combination of these markers.
Materials and Methods: This retrospective study included 62 cases diagnosed between 2010 and 2015, consisting of 29 primary lung adenocarcinoma (ADC), 19
squamous cell carcinoma (SCC), and 14 metastatic ADC to the lung. Immunohistochemical analyses for TTF-1, p40, p63, and MAdL were performed. Staining intensity
and the percentage of positive tumor cells were recorded with sensitivity and specificity values also calculated.
Results: TTF-1 showed high intensity and positivity in 79.31% of primary lung ADCs, with a sensitivity of 96.55% and specificity of 100%. p40 showed high intensity
staining in 84.21% of SCCs, with a sensitivity of 89.47% and specificity of 100%. p63 exhibited 100% sensitivity for SCC but low specificity (44.82%) due to focal
positivity in ADCs. MAdL had 82.75% sensitivity and 100% specificity for ADC. No marker positively stained metastatic ADCs.
Conclusion: Of the tested markers, TTF-1 showed the highest diagnostic accuracy for ADC and p40 for SCC. MAdL could serve as a supportive marker in ADC. p63
should considered with caution due to its low specificity. Particularly in small biopsy samples, to preserve tissue for molecular studies, a limited panel combining p40
and TTF-1 immunohistochemical markers is recommended for routine diagnostic use.