TITF-1 copy number gain(CNG) was detected by FISH analysis in both adenocarcinomas (18.9%; high CNG, 8.3%) and SCCs (20.1%; high CNG, 3.0%), and correlated significantly with the protein product (P = 0.004) and presence of KRAS mutations (P = 0.008) in lung adenocarcinomas.
DNAs extracted from frozen samples of the adenocarcinomas were examined for gene alterations, and TTF-1 expressions were determined using immunohistochemistry.
Ninety-two pulmonary adenocarcinomas (53 women and 39 men) confirmed by clinical presentation and positive immunohistochemistry for thyroid transcription factor-1 (TTF-1) were included in this study.
A panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, and a D-PAS stain for mucin increases diagnostic accuracy and agreement between pathologists when faced with refining a diagnosis of NSCLC to SQCC or ADC.
In contrast, patients with adenocarcinomas with TTF-1 expression had a worse outcome if TTF-1 was amplified (median overall survival time 39.5 versus 87.5 months).
Survival analysis showed that patients with stage I adenocarcinoma with TTF1 expression had a longer median overall survival than those without expression (n = 43, 44.3 v 26.2 months, P = .05 for the first cohort; n = 87; 49.7 v 38.5 months, P = .03 for the second cohort) Multivariate analysis revealed an independent lower risk of death for patients with stage I adenocarcinoma with TTF1-expressing tumors (hazard ratio = 0.479, 95% CI, 0.235 to 0.977; P = .043).
We have reported evidence implicating mutation specifically in the "terminal respiratory unit" type of adenocarcinoma, which is characterized by expression of thyroid transcription factor 1, a lineage marker of peripheral airway cells.
In subclasses, the expression rate of TTF-1 mRNA was obviously higher in PEs of patients with PPA (93.0%) than with metastatic pulmonary adenocarcinoma (0%) and with primary pulmonary squamous cell carcinoma (12.5%).
A recurrent gene fusion between EML4 and ALK in 6.7% of non-small cell lung cancers (NSCLCs) and NKX2-1 (TTF1, TITF1) high-level amplifications in 12% of adenocarcinomas of the lung were independently reported recently.
In this study, we investigated 14 intestinal type OMNs (borderline and adenocarcinoma) and 12 endocervical-like OMNs (borderline and adenocarcinoma) for their expression of PDX-1, CDX-2, CA-125, CK7, CK20, WT-1, D2-40, and TTF-1.
The specificity seems to be derived from transcription factor thyroid transcription factor 1-associating cofactors that affect human surfactant protein A1 promoter activity in pulmonary adenocarcinoma.
Among non-small cell lung carcinomas with clear cell features, 87.5% of adenocarcinomas (or 50% overall frequency in lung carcinomas) were positive for TTF-1, whereas none of the ovarian clear cell carcinomas were positive (P = 0.002).
These findings strongly suggest that in addition to the development and maintenance of TRU lineages in normal lung, sustained TTF-1 expression may be crucial for the survival of a subset of adenocarcinomas that express TTF-1, providing credence for the lineage-specific dependency model.
These tumors displayed morphological characteristics of human pulmonary adenocarcinoma such as their epithelial origin, tubulo-acinar architecture and expression of TTF-1, SP-B and proSP-C.
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.
Conclusively, these observations suggest that TTF-1 is a sensitive and specific diagnostic marker for pulmonary adenocarcinomas and SCLCs; that TTF-1 might have a good prognostic implication based on its inverse correlation with Ki-67 proliferative activity and tendency for better survival in NSCLC; that this cell lineage marker may play a role in the molecular pathogenesis of lung cancers at the level of transcription.
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.
Only one case of 99 adenocarcinomas that originated in various organs other than lung and thyroid immunohistochemically expressed thyroid transcription factor-1.