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Abstract 5221: TTF-1 status in early-stage lung adenocarcinoma is an independent predictor of relapse and survival superior to tumor grading

2024; American Association for Cancer Research; Volume: 84; Issue: 6_Supplement Linguagem: Inglês

10.1158/1538-7445.am2024-5221

1538-7445

Simon Schallenberg, Gabriel Dernbach, Mihnea P. Dragomir, Georg Schlachtenberger, Kyrill Boschung, Corinna Friedrich, Kai Standvoss, Lukas Ruff, Philipp Anders, Christian Grohé, Winfried Randerath, Sabine Merkelbach‐Bruse, Alexander Quaas, Matthias Heldwein, Ulrich Keilholz, Khosro Hekmat, Jens C. Rückert, Reinhard Büttner, David Horst, Frederick Klauschen, Nikolaj Frost,

RNA modifications and cancer

Abstract Background: Thyroid transcription factor 1 (TTF-1) is expressed in 70% to 80% of lung adenocarcinomas (LUAD). Several papers revealed that TTF-1 expression is associated with better patient outcomes independent of the tumor stage. However, it is unknown whether the prognostic impact of TTF-1 only results from a different growth pattern (tumor grading) or is independently associated with a biologically more aggressive phenotype. Thus, we analyzed a large bi-centric cohort of LUAD to assume the true prognostic value of TTF-1 in relation to the tumor grade. Methods: We collected a large, real-life cohort of 447 patients with completely resected LUAD from two large-volume German lung cancer centers. TTF-1 status, evaluated by IHC, and tumor grading were correlated with clinical, pathologic, and molecular data, as well as patient outcomes. Kaplan-Meier curves were used for comparison of TTF-1 status and different tumor grades in terms of the DFS. The impact of TTF-1 was measured by univariate and multivariate Cox regression. Finally, a causal graph analysis was performed to identify and account for potential confounders to improve the statistical estimation of the predictive power of TTF-1 expression for DFS in comparison to the tumor grade. Results: Kaplan-Meier curves revealed that TTF-1 positivity is associated with longer DFS independent of tumor grade, whereas a strong association of DFS with the tumor grade is observed only in TTF-1-positive patients. In univariate analysis, TTF-1 positivity was associated with significantly longer DFS (median log HR -0.83 [-1.43; -0.20]; p=0.018), whereas higher tumor grade showed a non-significant association with shorter DFS (median log HR 0.30 [-0.58; 1.60]; p=0,62 for G1 to G2 and 0.68 [-0.24; 1.89]; p=0,34 for G2 to G3). In multivariate analysis, TTF-1 positivity resulted in a significantly longer DFS (median log HR -0.65 [-1.13; -0.09]; p=0.05) independent of all other parameters, including tumor grade. Applying the adjustment sets suggested by the causal graph analysis, the superiority of TTF-1 (median log HR -0.86 [-1.25; -0.41]) over tumor grade (median log HR 0.31 [-0.32; 1.30]/0.61[-0.07; 1.65]) in terms of prognostic power was confirmed. Conclusion: This study draws three important conclusions: Firstly, it indicates that the prognostic power of tumor grade is limited to TTF-1-positive patients. Secondly, it underlines the independent prognostic value of TTF-1 expression for DFS regardless of tumor grade. Finally, our analyses reveal that the effect size of TTF-1 surpasses that of tumor grade. To transfer the results directly into the clinical area, we recommend distinguishing between TTF-1-positive and TTF-1-negative LUADs in the pathological report. Tumor grading should only be applied to TTF-1-positive LUADs (TTF-1+/G1-3). TTF-1-negative LUADs should either not be graded or always be classified as high-grade (TTF-1-/G3). Citation Format: Simon Schallenberg, Gabriel Dernbach, Mihnea Dragomir, Georg Schlachtenberger, Kyrill Boschung, Corinna Friedrich, Kai Standvoss, Lukas Ruff, Philipp Anders, Christian Grohe, Winfried Randerath, Sabine Merkelbach-Bruse, Alexander Quaas, Matthias Heldwein, Ulrich Keilholz, Khosro Hekmat, Jens Rückert, Reinhard Büttner, David Horst, Frederick Klauschen, Nikolaj Frost. TTF-1 status in early-stage lung adenocarcinoma is an independent predictor of relapse and survival superior to tumor grading [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5221.