Our findings suggest that TTF-1 promotes SCLC growth and contributes to neuroendocrine and antiapoptotic gene expression by partly coordinating with ASCL1.
Based on this study, we propose the following algorithm, which, in the appropriate clinical and histological context, may be useful in establishing the correct diagnosis of SCLC: First, INSM1 detection is performed, and if the result is negative, CD56 is added, followed successively by p16 and TTF1 if all previously applied markers are negative.
The p63 positivity and TTF-1 negative expression consequently indicated a poorly differentiated nonkeratinizing SCC, while the opposite immunostaining pattern was flagged in SCLC.
Combination of CD56, p16 and TTF1 produced diagnostic classifier that outperformed best single marker CD56 in differential diagnosis between SCLC and NSCLC.
The TTF-1 expression of pulmonary SCC illustrating diffuse and strong positivity in tumor cell nuclei was significantly higher than that of the cervical SCC (P = .003).
Using model-based clustering, we found two major proteomic subtypes of SCLC characterized by either high thyroid transcription factor-1 (TTF1)/low cMYC protein expression or high cMYC/low TTF1.
It has been suggested that thyroid transcription factor-1 (TTF-1) is frequently expressed in human lung cancer, especially in adenocarcinoma and small cell lung cancer, and the TTF-1 expression is closely related with the expression of surfactant protein.
In contrast, cytoplasmic staining of TTF-1 was observed in five of six adenocarcinoma cell lines, in six of seven small cell lung cancer cell lines, and in all three squamous cell lung cancer cell lines.