OBJECTIVETo investigate the computed tomographic (CT) and pathological features of primary pulmonary sarcomatoid carcinoma (PSC).

METHODSThe clinical data and CT images of 20 patients with pathologically confirmed PSC were retrospectively analyzed.

RESULTSSolitary pulmonary mass was identified in 18 patients and multiple pulmonary masses in 2 patients, amounting to 22 masses. There were 17 peripheral masses and 5 central masses, including 11 masses larger than 5 cm. The smooth margin was identified in 9 masses, deep lobulation and/or spinous protuberance in 11 masses, and ill-defined margin in 2 masses. Pleural indentation was identified in 2 masses and pleural thickening with wide basement was identified in 14 masses. On plain CT, cavity was observed in 5 masses, hypo-density in 7 masses, and homogeneous density in 10 masses. On contrast-enhanced CT scanning, irregular ring/patchy enhancement were shown in 15 masses and slightly homogenous enhancement in 2 masses. Of all patients, 6 patients had unilateral or bilateral hilar and/or mediastinal lymphadenopathy. There were 16 pleomorphic carcinomas and 4 spindle cell carcinomas. Immunohistochemically, anti-pan cytokeratin antibody was positive in 13 patients, cytokeratin was positive in 8 patients, Vimentin was positive in 15 patients, epithelial membrane antigen was positive in 1 patient, and thyroid transcription factor-1 was positive in 8 patients.

CONCLUSIONPSC has some specific CT features; however, the final confirmation of PSC still depends on pathological and immunohistochemical examinations.

Humans ; Lung Neoplasms ; pathology ; Nuclear Proteins ; Retrospective Studies ; Sarcoma ; Thyroid Nuclear Factor 1 ; Tomography, X-Ray Computed ; Transcription Factors

Targeted gene therapy has become a promising approach for lung cancer treatment. In our previous work, we reported that the targeted expression of microRNA-7 (miR-7) operated by thyroid transcription factor-1 (TTF-1) promoter inhibited the growth of human lung cancer cells in vitro and in vivo; however, the intervention efficiency needed to be further improved. In this study, we identified the core promoter of TTF-1 (from -1299 bp to -871 bp) by 5' deletion assay and screened out the putative transcription factors nuclear factor-1 (NF-1) and activator protein-1 (AP-1). Further analysis revealed that the expression level of NF-1, but not AP-1, was positively connected with the activation of TTF-1 core promoter in human non-small-cell lung cancer (NSCLC) cells. Moreover, the silencing of NF-1 could reduce the expression level of miR-7 operated by TTF-1 core promoter. Of note, we optimized four distinct sequences to form additional NF-1-binding sites (TGGCA) in the sequence of TTF-1 core promoter (termed as ^optTTF-1 promoter), and verified the binding efficiency of NF-1 on the ^optTTF-1 promoter by electrophoretic mobility shift assay (EMSA). As expected, the ^optTTF-1 promoter could more effectively drive miR-7 expression and inhibit the growth of human NSCLC cells in vitro, accompanied by a reduced transduction of NADH dehydrogenase (ubiquinone) 1α subcomplex 4 (NDUFA4)/protein kinase B (Akt) pathway. Consistently, ^optTTF-1 promoter-driven miR-7 expression could also effectively abrogate the growth and metastasis of tumor cells in a murine xenograft model of human NSCLC. Finally, no significant changes were detected in the biological indicators or the histology of some important tissues and organs, including heart, liver, and spleen. On the whole, our study revealed that the optimized TTF-1 promoter could more effectively operate miR-7 to influence the growth of human NSCLC cells, providing a new basis for the development of microRNA-based targeting gene therapy against clinical lung cancer.
Animals ; Humans ; Mice ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/metabolism* ; MicroRNAs/metabolism* ; Nuclear Proteins/metabolism* ; Thyroid Gland/pathology* ; Thyroid Nuclear Factor 1/genetics* ; Transcription Factors/metabolism*

Brain-lung-thyroid syndrome is a rare autosomal dominant disorder. More than 100 cases have been reported worldwide, but few cases have been reported in China. In December 2018, a boy with brain-lung-thyroid syndrome, aged 3 years and 10 months, was admitted to Xiangya Hospital of Central South University due to repeated cough for more than 3 years. In infancy of the boy, psychomotor retardation, repeated cough, and hypothyroidism were found. Gene detection showed that there was c.927delc heterozygous variation in NKX2-1 gene (NM-001079668: exon3: c.927delC). The variation of this gene locus has not been reported in relevant literature so far, which indicates a new mutation. According to the above clinical manifestations and examination results, the boy was diagnosed as brain-lung-thyroid syndrome, which mainly characterized by nervous system disorders, accompanied by respiratory manifestations and hypothyroidism. The boy was treated with oral dopasehydrazine to relieve tremor and levothyroxine sodium tablets to relieve hypothyroidism. Anti-infection, atomization, rehabilitation training and other symptomatic supporting treatment were also administered. The boy's language and movement have improved, the thyroid hormone level is normal, and there are still repeated respiratory tract infections.
Athetosis/genetics* ; Chorea ; Congenital Hypothyroidism/genetics* ; Cough ; Humans ; Male ; Respiratory Distress Syndrome, Newborn ; Thyroid Nuclear Factor 1/genetics*

OBJECTIVERecent progress in developmental biology has shown that the thyroid transcription factor-1 (TTF-1) plays an important role in lung development. The aim of this study was to investigate the expression and distribution of TTF-1 and its function during the development of epithelial stem cells in fetal human lungs.

METHODSHuman lung tissues were obtained with parental consent from 32 fetuses (10-27 weeks) and from seven newborn infants (28-36 weeks) who had not died from pulmonary diseases. The expression of TTF-1 was examined by immunohistochemistry.

RESULTSTTF-1 was expressed in the nuclei of columnar nonciliated epithelial cells of the fetal human lung as early as 10 weeks of gestation. With the development of bronchus TTF-1 positive cells were present in scattered nonciliated cells and were predominantly expressed in the nuclei of epithelial cells of the distal tubules and lung buds. By the late phase of fetal development or neonatal period, TTF-1 was expressed in only type II alveolar epithelium cells and their precursor cells but was absent in ciliated cells and type I alveolar epithelium cells.

CONCLUSIONSTTF-1 can stimulate the growth of both bronchial trees and alveolar cells and regulate the type II alveolar epithelium cells and their precursors to secret surfactants.

Epithelial Cells ; chemistry ; cytology ; Female ; Fetus ; chemistry ; Humans ; Immunohistochemistry ; Infant, Newborn ; Lung ; chemistry ; cytology ; embryology ; Male ; Nuclear Proteins ; analysis ; Thyroid Nuclear Factor 1 ; Transcription Factors ; analysis

OBJECTIVETo evaluate serum Nkx2-1 (NKX homeobox-1) levels in diagnosis of primary lung cancer.

METHODSThe serum NKX2-1 and CEA (carcinoma embryonic antigen) levels were measured in 61 patients with primary lung cancer admitted from May 2009 to December 2010 and 49 healthy individuals served as controls. The receiver operating characteristic curve (ROC) of NKX2-1 in diagnosis for primary lung cancer was analyzed. The value of serum NKX2-1 in diagnosing primary lung cancer was compared with that of CEA by X(2) test and Kappa test.

RESULTSThe serum Nkx2-1 levels in lung cancer were significantly higher than those in controls [(1.4206 ±0.1257)ng/ml compared with (0.7646 ±0.0734)ng/ml,P<0.01]. ROC analysis showed the area under the curve of serum NKX2-1 was 0.859. The Kappa value of NKX2-1 was higher than that of CEA (0.586 compared with 0.396,P<0.05). Combination of serum NKX2-1 with CEA improved the Kappa value to 0.704, and also had high sensitivity (83.6%) and specificity (87.0%) for diagnosis of primary lung cancer.

CONCLUSIONSerum NKX2-1 protein can be used as a marker for diagnosis of lung cancer, the combination of NKX2-1 with CEA may further improve the diagnostic value.

Biomarkers, Tumor ; blood ; Carcinoembryonic Antigen ; blood ; Case-Control Studies ; Humans ; Lung Neoplasms ; blood ; diagnosis ; Nuclear Proteins ; blood ; Sensitivity and Specificity ; Thyroid Nuclear Factor 1 ; Transcription Factors ; blood

OBJECTIVETo investigate the significance of thyroid transcription factor-1 (TTF-1) in the histogenesis of pulmonary sclerosing hemangioma (PSH).

METHODSWith clinicopathologic data of 36 PSH patients obtained, all specimens were stained by immunohistochemical method with a panel of antibodies including TTF-1, SpA, CK, EMA, F-VIII, CD34, Claretinin, HBME, synaptophsin, chromogranin, actin and S-100.

RESULTSThe patients were mostly women with a mean age of 46.7 years and a median age of 48 years. All lesions were solitary and well circumscribed with a mean size of 3.3 cm and a median size of 3 cm. No multiple or metastasis was found. Surface cells (SC) and round cells (RC) were showed in PSH, with more than 90% showing TTF-1 and EMA by immunohistochemical method. CK and SpA were showed in SC, which were not showed in RC. Neuroendocrine cells scattered within RC of PSH were detected in a few cases. Mesothelial, vascular endothelial, neuroendocrine, and myoepithelial markers by immunohistochemical method were negative.

CONCLUSIONPulmonary sclerosing hemangioma, a benign tumor, originates from the alveolar pneumocytes. Its surface cells are more mature, while the round cells, being primitive respiratory epithelia, may undergo phenotypic differentiation and evolve into mucinous glands or neuroendocrine structure among other components.

Adult ; Aged ; Female ; Hemangioma ; metabolism ; pathology ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Nuclear Proteins ; metabolism ; Sclerosis ; etiology ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism

OBJECTIVETo investigate the variation of serum thyroid transcription factor-1 (TTF-1) in different patients and explore its significance in the diagnosis of lung carcinoma.

METHODSDot-enzyme linked immunosorbent assay (dot-ELISA) and Leica Q500 MC image analysis system were used to quantitatively detect TTF-1 protein in the serum samples from normal healthy adults and from patients with benign lung disease, lung cancer, thyroid carcinoma and non-thyroid carcinoma.

RESULTSThe sensitivity, specificity, standardized positive predicative value, standardized negative predicative value, standardized accuracy and standardized wrong diagnostic rate of the method were 90.91%, 82.22%, 83.64%, 90.04%, 86.57% and 13.43%, respectively. The cutoff value of serum TTF-1 in healthy normal adults was 36.39, with a ROC value of 0.95. Serum TTF-1 PU was significantly higher in patients with lung adenocarcinoma, squamous cell lung carcinoma and thyroid carcinoma than in healthy adults and patients with benign lung diseases and non-thyroid carcinoma (P=0.000). Serum TTF-1 PU was similar in lung adenocarcinoma, squamous cell lung carcinoma, small cell lung carcinoma, large cell lung carcinoma and thyroid carcinoma (P=0.744, 0.677, and 0.333, respectively). Serum TTF-1 PU was greater than the PU in the corresponding homogenate of lung adenocarcinoma, squamous cell lung carcinoma, small cell lung carcinoma, large cell lung carcinoma and thyroid carcinoma (P=0.000). Serum and homogenate TTF-1 PU was correlated to TNM stage of lung cancer patients (P=0.000) but not to gender, tumor types, differentiation or lymph node metastasis.

CONCLUSIONSLung adenocarcinoma, squamous cell lung carcinoma and thyroid carcinoma are suspected when serum TTF-1 PU is higher than 36.39. Serum TTF-1 is not helpful in differentiating the types of lung carcinomas and thyroid carcinoma. After exclusion of thyroid carcinoma, detection of serum TTF-1 can be helpful in the diagnosis of lung cancer. In different lung carcinomas and thyroid carcinomas, the serum TTF-1 is higher than the corresponding homogenate TTF-1 level. Serum TTF-1 increases with the progression of TNM stage of lung carcinoma.

Case-Control Studies ; Humans ; Lung Neoplasms ; blood ; classification ; diagnosis ; Nuclear Proteins ; blood ; Predictive Value of Tests ; Sensitivity and Specificity ; Thyroid Nuclear Factor 1 ; Transcription Factors ; blood

OBJECTIVETo observe the expression of thyroid transcription factor-1 (TTF-1) mRNA in human normal adult type II alveolar epithelial cells, embryonic alveolar epithelial cells, and primary lung carcinoma and lymph nodes, thereby exploring the role of TTF-1 mRNA expression in the tumorigenesis, development and metastasis of lung carcinoma.

METHODSTTF-1 mRNA was detected using tissue microarray and in situ hybridization in 1320 different paraffin-embedded tissue specimens. The intensity of TTF-1 mRNA in these tissues was assessed quantitatively using Leica Q500MC image analysis system.

RESULTSTTF-1 mRNA expression was significantly less intense in embryonic lung than in normal adult lung tissues (P= 0.000), and the two tissues both had significantly greater expression than lung adenocarcinoma, squamous cell carcinoma, small cell carcinoma and large cell carcinoma (P=0.000). Lung adenocarcinoma and small cell carcinoma, with similar expression intensity (P= 0.068), showed stronger expression than squamous cell carcinoma and large cell carcinoma (P=0.000), and squamous cell carcinoma showed stronger expression than large cell carcinoma (P=0.018). In lung adenocarcinoma, squamous cell carcinoma and large cell carcinoma, the intensity of TTF-1 mRNA expression was stronger in lymph node metastases than in the primary foci (P=0.003, P=0.000, P=0.019, respectively). The lymph node metastases had more intense expression than the primary foci of small cell lung carcinoma (P=0.078). The intensity of TTF-1 mRNA expression was greater in primary lung carcinomas with lymph node metastases than in those without metastases (P=0.026). Tumors of TNM stage II-IV had stronger expression than those of stage I (P=0.010). The intensity of TTF-1 mRNA expression was not associated with the patients' gender or the general types and differentiation of the tumor.

CONCLUSIONThe amount of TTF-1 mRNA expression lowers in the order of normal adult lung, embryonic lung and lung carcinoma tissues. In lung carcinomas, TTF-1 mRNA expression differs between the histological types, high in lung adenocarcinoma and small cell carcinoma and rather low in squamous cell carcinoma and large cell carcinoma. Strong expression of TTF-1 mRNA often indicates high likeliness of lung carcinoma metastasis, and highlights the high metastatic potentials of lung adenocarcinoma, squamous cell carcinoma and large cell carcinoma.

Adenocarcinoma ; genetics ; pathology ; Carcinoma, Squamous Cell ; genetics ; pathology ; Female ; Humans ; In Situ Hybridization ; Lung Neoplasms ; genetics ; pathology ; Lymphatic Metastasis ; Male ; Nuclear Proteins ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Thyroid Gland ; metabolism ; Thyroid Nuclear Factor 1 ; Tissue Array Analysis ; methods ; Transcription Factors ; genetics

Solitary fibrous tumor (SFT) is a derived mesenchymal tumor from spindle cells, mostly occurred in the pleura. To analyze the clinical features of the SFT, data for a patient with SFT that involved in the pleura were retrospectively analyzed by assisted thoracoscope in the Affiliated Hospital of Zunyi Medical College in August 2015. The male patient was 45 years old, who showed the main clinical symptoms of chest pain, cough, sputum, and dyspnea. Large amount of right pleural effusion, chest space-occupying lesions were found by chest CT, suggesting a malignant tumor with metastasis at the 2nd and 3rd right rib. Immunohistochemical results showed: CD34 (+), cytokeratin (-), cytokeratin 5/6 (-), calretinin (-), epithelial membrane antigen(-), mesothelial cell (-), vimentin (++), Wilm's tumor-1 (+), Bcl-2 (+), CD56 (-), CD99 (+), desmin (-), and thyroid transcription factor-1 (-). It was diagnosed as SFT at right side wall layer pleura. SFT is a rare disease and it may occur at any site in the body. It lacks characteristic clinical symptoms and can be asymptomatic, or displays symptoms such as cough, chest pain, dyspnea, and hemoptysis. SFTs can only be conclusively diagnosed based on histopathologic and immunohistochemical characteristics of the tumor, and they are mostly benign. The main treatment for SFTs is the complete surgical resection. The prognosis for this disease is relatively good.
Calbindin 2 ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prognosis ; Solitary Fibrous Tumor, Pleural ; diagnosis ; surgery ; Thyroid Nuclear Factor 1 ; Tomography, X-Ray Computed

OBJECTIVETo investigate the value of detecting thyroid transcription factor 1 (TTF-1) and Noval aspartic proteinase of pepsin family A (napsin A) in pleural fluid cell blocks in cytopathologic diagnosis of pulmonary adenocarcinoma.

METHODSConventional cell smears of pleural effusions were obtained from 48 patients with a history of lung adenocarcinoma for cytological analysis. The cell blocks were prepared using the cytological specimens and examined with immunohistochemistry for TTF-1 and napsin A. The rates of a positive diagnosis of pulmonary adenocarcinoma were compared between the two methods, and the diagnositic value of TTF-1 and napsin A in pleural fluid cell blocks was evaluated.

RESULTSImmuno- histochemistry of the cell block sections yielded a significantly higher positive rate of diagnosis than cytological analysis of conventional cell smear (84.44% vs 55.56%, P<0.05). Most of the pleural fluid cell blocks showed positive expressions of TTF-1 (36/38, 94.74%) and napsin A (30/38, 78.95%), and none of samples showed TTF-1 or napsin A expression in the mesothelial cells (P<0.05). The combination detection of TTF-1 and napsin A in pleural fluid cell blocks had a high diagnosis value with a diagnostic sensitivity of 97.37% and a specificity of 100% for pulmonary adenocarcinoma.

CONCLUSIONSThe combined detection of TTF-1 and napsin A in pleural fluid cell blocks facilitates cytopathologic diagnosis of pulmonary adenocarcinoma.

Adenocarcinoma ; diagnosis ; metabolism ; Aspartic Acid Endopeptidases ; metabolism ; Biomarkers, Tumor ; metabolism ; Humans ; Immunohistochemistry ; Lung Neoplasms ; diagnosis ; metabolism ; Nuclear Proteins ; metabolism ; Pleural Effusion ; Sensitivity and Specificity ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism