TTF-1 negativity in synchronous M1b/M1c wildtype lung adenocarcinoma brain metastases predicts worse survival with increased risk of intracranial progression

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2024年12月4日

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David Wasilewski,
Tommaso Araceli,
Philip Bischoff,
Anton Früh,
Rober Ates,
Selin Murad,
Niklas Jung,
Jan Bukatz,
Majd Samman,
Katharina Faust,
Julia Jünger,
Martin Witzenrath,
David Horst,
Atik Baborie,
Arend Koch,
David Capper,
Frank L. Heppner,
Helena Radbruch,
Markus J. Riemenschneider,
Nils Ole Schmidt,
Peter Vajkoczy,
Martin Proescholdt,
Julia Onken,
Nikolaj Frost

摘要

Background

Thyroid Transcription Factor-1 (TTF-1) expression in lung adenocarcinoma (LUAD) has been studied for its prognostic value in early-stage and metastatic disease. Its role in brain metastasis remains unexplored. This study investigates the predictive value and association of TTF-1 status with clinicopathological variables in patients with synchronous LUAD brain metastases.

Material and methods

In this bicentric retrospective study, 245 patients with newly diagnosed, treatment-naïve brain metastasis undergoing resection were included. Patient data were retrieved from electronic records. Outcomes included overall and progression-free survival. Statistical analysis included Kaplan–Meier estimates and Cox proportional hazards regression.

Results

Mean Ki67 index in TTF-1 negative patients was 43% [95% CI 38–48%] compared to 32% [95% CI 29–35%] in TTF-1 positive (TTF-1 +) patients (p < 0.001). Tumor volume was significantly larger in TTF-1 negative (TTF-1-) patients (mean volume 24 mL [95% CI 18–31 mL]) vs. 15 mL [95% CI 12–17 mL] in TTF-1 + patients (padjust = 0.003). Perifocal edema was smaller in TTF-1- patients (mean volume: 58 mL [95% CI 45–70 mL]) vs. 84 mL [95% CI 73–94 mL] in TTF-1 + patients (padjust = 0.077). Tumor and edema volume did not correlate. TTF-1- patients showed worse overall, intracranial, and extracranial progression-free survival. In a multivariable Cox model, positive TTF-1 status was independently associated with improved outcomes. Negative TTF-1 status was associated with increased hazard for intracranial disease progression compared to extracranial progression.

Conclusion

In synchronous LUAD brain metastases, TTF-1 negativity reflects an aggressive phenotype with larger proliferation capacity and tumor volume. Future research should explore the underlying cellular and molecular alterations of this phenotype.