TTF1 (Transcription Termination Factor 1)

TTF-1 negativity identifies a subset of LUAD with worse outcomes to immunotherapy, chemo-immunotherapy, and KRASG12C inhibitors.

Notably, SYNE1, TMEM132C, and TNN were identified as characteristic mutations, defining a distinct mutational profile that sets this rare subtype apart from both SCC and ADC. Our findings highlight that NSCLC with diffuse co-expression of TTF-1 and p40 probably constitutes a distinct clinicopathological subtype with rapid clinical progression and poor prognosis, defined by unique morphological characteristics, a biphenotypic immunoprofile, and specific molecular alterations.

The tumor cells additionally exhibited immunoreactivity for TTF-1 (also known as NKX2.1), which has been reported to be expressed in GABAergic precursor cells in the medial ganglionic eminence. This example may provide at least a small insight into embryonic origins of supratentorial AT/RT.

This case highlights the diagnostic challenge posed by TTF-1-positive gastric tumors, which may be mistaken for metastatic lesions from lung cancer. As TTF-1 expression is not entirely specific to tissues of lung or thyroid origin, diagnosis should be based on a comprehensive evaluation of morphological and immunohistochemical findings, together with clinical information, including treatment response and disease course.

Columnar cell carcinoma (CCC-PTC) is a rare subtype of PTC that is characterized by hypercellularity and pseudostratification. Co-expression of TTF-1 and CDX-2 is a useful clue to its diagnosis.

Next-generation sequencing analysis confirmed ALK rearrangements in 3 cases. Accurate identification of this specific subtype of lung adenocarcinoma is essential for administering appropriate treatment and reducing the risk of potential misdiagnosis.

TRIM29 is a promising biomarker for NSCLC, particularly in differentiating SCC from ADC. Its strong association with p40, coupled with an inverse relationship with TTF1, enhances its diagnostic utility. Further studies are needed to explore its role in lung cancer pathogenesis and prognosis.

Unlike SCLC, lung carcinoids and EP-NETs completely lack the expression of POU2F3 and YAP1, which offers diagnostic applications. Our findings also nominate ASCL1 and NEUROD1 as site of origin markers for lung versus digestive NETs/carcinoids, respectively. Finally, the divergent expression of DLL3 in lung carcinoids and EP-NETs has therapeutic implications.

Platinum and pemetrexed combined with pembrolizumab remains an effective first-line treatment option for lung adenocarcinoma, regardless of TTF-1 expression.

RSV and 3-MET-OX reduced stemness markers (SOX2, NANOG), increased the thyroid lineage transcription factor (SOX17), and enhanced differentiation genes (TTF-1, TPO, NIS). Overall, these results support our hypothesis that modulation of the SOX2/SOX17 ratio by polyphenols provides a mechanistic basis for re-differentiation, thereby improving therapeutic responsiveness in ATC.

Colloid cysts of the 3rd ventricle are consistently PAX8-positive, while they lack signs of thyroid, müllerian or enteric differentiation. Furthermore, PAX8 can be used to distinguish CC from NEC, RCC, and craniopharyngiomas.

Subset analysis showed that the TTF-1-positive group exhibited significantly longer PFS than the negative group in both the ICI monotherapy (median PFS, 17.6 months vs. 2.9 months, P<0.001, log-rank test) and chemoimmunotherapy (median PFS, 10.4 months vs. 5.2 months, P=0.021, log-rank test) groups. In conclusion, the current study observed an association between TTF-1 expression evaluated using a cocktail antibody and the effectiveness of treatment with ICI monotherapy or chemoimmunotherapy.