Prognostic Effect of TTF-1 Expression and Histopathology in the Patients with Advanced Lung Adenocarcinoma Treated with Immunochemotherapy.

OBJECTIVES: The International Association for the Study of Lung Cancer (IASLC) proposed a grading system based on predominant histologic subtypes and reflecting prognosis. We previously reported that thyroid transcription factor-1 (TTF-1) expression levels and tumor cell proportion are useful predictors of immunochemotherapy for lung adenocarcinoma. Building upon our previous findings that TTF-1 negativity was associated with poorer outcomes in patients receiving immunochemotherapy, this study further investigated the relationship between TTF-1 expression and IASLC histologic subtypes, and analyzed progression-free survival (PFS) according to TTF-1 expression within each histologic subtype. MATERIALS AND METHODS: We used the same multicenter retrospective dataset as in our previous study, which was conducted between January 2019 and May 2023. TTF-1 was considered positive as a predictive factor of immunochemotherapy when staining showed high TTF-1 expression. The association between TTF-1 expression, histologic subtype, and mucus-producing components was evaluated. RESULTS: Among 95 patients, the positivity rate for TTF-1 was 61.1%. The negative rate of TTF-1 in mucus-producing adenocarcinomas was significantly higher than that in non-mucus-producing adenocarcinomas (18/29 [62.1%] vs. 18/63 [28.6%]; p < 0.01). As per the analysis of IASLC grade 3, the median PFS of TTF-1 negative patients was significantly worse than that of positive patients (6.0 vs. 7.6 months, p = 0.035). Among patients with solid predominant patterns, the median PFS was significantly worse in the patients with TTF-1 negative than positive (5.2 vs. 8.5 months, p = 0.014). CONCLUSION: This study shows that the combination of histopathology and TTF-1 expression is a predictive factor in patients treated with combined immunochemotherapy.