Clinical significance of blood lipids, lipoproteins, PTX-3, TTF-1, NSE, and CYFRA21-1 levels in patients with advanced gastric cancer / 中国医师杂志

Objective:To investigate the significance of blood lipids [triglyceride (TG), total cholesterol (TC)], lipoproteins [high-density lipoprotein (HDL), low-density lipoprotein (LDL)], and serum levels of pentraxin-3 (PTX-3), thyroid transcription factor-1 (TTF-1), neuron specific enolase (NSE), and human cytokeratin 21-1 fragment (CYFRA21-1) in patients with advanced gastric cancer, and to provide a basis for the early, middle, and late diagnosis and treatment of gastric cancer.Methods:127 gastric cancer patients admitted to 3201 Hospital from January 2019 to January 2022 were selected as the research subjects. They were divided into early stage group ( n=45), mild stage group ( n=43), and late stage group ( n=39) based on their condition. Enzyme linked immunosorbent assay (ELISA) was used to detect blood lipids (TG, TC), PTX-3, TTF-1, NSE, CYFRA21-1, and chemical precipitation method was used to detect lipoprotein metabolism (HDL, LDL) in the three groups of patients. The differences in blood lipids, lipoproteins, PTX-3, TTF-1, NSE, and CYFRA21-1 between three groups of gastric cancer patients and the late stage group of gastric cancer patients before and after surgery were analyzed. Logistic regression analysis was conducted to investigate the correlation between blood lipids (TG, TC), lipoprotein (HDL, LDL), PTX-3, TTF-1, NSE, CYFRA21-1, and gastric cancer incidence. The predictive value of individual and combined detection of the above indicators for gastric cancer was analyzed using the receiver operating characteristic (ROC) curve analysis. Results:The results showed that the TG, TC, and LDL levels in the late stage group were higher than those in the mild stage and early stage groups (all P<0.05), while the HDL levels were lower than those in the mild stage and early stage groups (all P<0.05). The serum levels of PTX-3, TTF-1, NSE, and CYFRA21-1 were higher than those in the mild stage and early stage groups (all P<0.05). The postoperative levels of TG, PTX-3, TTF-1, NSE, CYFRA21-1, TC, and LDL in the late stage group were significantly lower than those before surgery (all P<0.05) and the HDL level was higher than that before surgery ( P<0.05). The levels of TG, TC, HDL, LDL, PTX-3, TTF-1, NSE, and CYFRA21-1 were correlated with the late onset of gastric cancer (all P<0.05). The ROC curve showed that the area under the ROC curve (AUC) of PTX-3, TTF-1, NSE, and CYFRA21-1 combined detection was significantly higher than that of PTX3, TTF1, NSE, and CYFRA211 alone. Among them, PTX-3+ TTF-1+ NSE+ CYFRA21-1 combined detection had the highest AUC, sensitivity, and specificity. Conclusions:Patients with advanced gastric cancer have abnormal levels of blood lipids (TG, TC), lipoprotein (HDL, LDL), and serum PTX-3, TTF-1, NSE, and CYFRA21-1. Effective intervention measures need to be developed based on the above indicators to improve survival rate.

Clinical value of a differentiation prediction model for invasive lung adenocarcinoma / 中华肿瘤杂志

Objective: To investigate the value of predicting the degree of differentiation of pulmonary invasive adenocarcinoma (IAC) based on CT image radiomics model and the expression difference of immunohistochemical factors between different degrees of differentiation of lesions. Methods: The clinicopathological data of patients with pulmonary IAC confirmed by surgical pathology in the Affiliated Huai'an First People's Hospital to Nanjing Medical University from December 2017 to September 2018 were collected. High-throughput feature acquisition was performed for all outlined regions of interest, and prediction models were constructed after dimensionality reduction by the minimum absolute shrinkage operator. Receiver operating characteristic curve was used to assess the predictive efficacy of clinical characteristic model, radiomics model and individualized prediction model combined with both to identify the degree of pulmonary IAC differentiation, and immunohistochemical expressions of Ki-67, NapsinA and TTF-1 were compared between groups with different degrees of IAC differentiation using rank sum test. Results: A total of 396 high-throughput features were extracted from all IAC lesions, and 10 features with high generalization ability and correlation with the degree of IAC differentiation were screened. The mean radiomics score of poorly differentiated IAC in the training group (1.206) was higher than that of patients with high and medium differentiation (0.969, P=0.001), and the mean radiomics score of poorly differentiated IAC in the test group (1.545) was higher than that of patients with high and medium differentiation (-0.815, P<0.001). The differences in gender (P<0.001), pleural stretch sign (P=0.005), and burr sign (P=0.033) were statistically significant between patients in the well and poorly differentiated IAC groups. Multifactorial logistic regression analysis showed that gender and pleural stretch sign were related to the degree of IAC differentiation (P<0.05). The clinical feature model consisted of age, gender, pleural stretch sign, burr sign, tumor vessel sign, and vacuolar sign, and the individualized prediction model consisted of gender, pleural stretch sign, and radiomic score, and was represented by a nomogram. The Akaike information standard values of the radiomics model, clinical feature model and individualized prediction model were 54.756, 82.214 and 53.282, respectively. The individualized prediction model was most effective in identifying the degree of differentiation of pulmonary IAC, and the area under the curves (AUC) of the individualized prediction model in the training group and the test group were 0.92 (95% CI: 0.86-0.99) and 0.88 (95% CI: 0.74-1.00, respectively). The AUCs of the radiomics group model for predicting the degree of differentiation of pulmonary IAC in the training group and the test group were 0.91 (95% CI: 0.83-0.98) and 0.87 (95% CI: 0.72-1.00), respectively. The AUCs of the clinical characteristics model for predicting the degree of differentiation of pulmonary IACs in the training and test groups were 0.75 (95% CI: 0.63-0.86) and 0.76 (95% CI: 0.59-0.94), respectively. The expression level of Ki-67 in poorly differentiated IAC was higher than that in well-differentiated IAC (P<0.001). The expression levels of NapsinA, TTF-1 in poorly differentiated IAC were higher than those in well-differentiated IAC (P<0.05). Conclusions: Individualized prediction model consisted of gender, pleural stretch sign and radiomics score can discriminate the differentiation degree of IAC with the best performance in comparison with clinical feature model and radiomics model. Ki-67, NapsinA and TTF-1 express differently in different degrees of differentiation of IAC.

The prognostic role of thyroid transcription factor-1 in lung adenocarcinoma

Aims: In this study, we investigated the expression of thyroid transcription factor-1 (TTF-1) in lung adenocarcinoma patients' samples and analyzed the association of TTF-1 with clinicopathological parameters, prognosis, and treatment options in patients with lung adenocarcinoma. Subjects and Methods: This retrospective study enrolled 200 patients who were histologically confirmed lung adenocarcinoma with Stage I-IV disease, between 2008 and 2015 years. The cytological archive of these hospitals' Pathology Department was searched. The available slides and the clinical information were reviewed and correlated. All analyses were conducted by SPSS version 15.0 statistical software. Results: Sixty-five (32.5%) of the patients showed TTF-1 negativity and 135 (67.5%) of them showed TTF-1 positivity. The median survival for TTF-1 positive and negative patients was 19.6 and 12.2 months, respectively. We did not find any statistical significance in-between the parameters in terms of the survival data. In TTF-1-negative group, the survival time of epidermal growth factor receptor mutation positive (P = 0.049), cytokeratin 7 (CK7) positive (P = 0.009) patients and those who had received curative radiotherapy (P = 0.028) was significantly better as compared to TTF-1-positive group. We also analyzed the relation between TTF-1 and survival outcome or chemotherapy selection in Stage IV disease. We could not identify any correlation between TTF-1 and survival outcome or treatment selection. Conclusions: This study suggests that TTF-1 is not a favorable prognostic factor in lung adenocarcinoma patients. The prognostic role of CK7 and relationship between TFF-1 expression in lung adenocarcinoma and predictive role of TTF-1 expression for the selection of first-line treatment in Stage IV lung adenocarcinoma should be validated in prospective and randomized studies

Expression of thyroid transcription factor 1 in patients with lung adenocarcinoma and its correlation with the prognosis of patients with advanced lung adenocarcinoma / 肿瘤研究与临床

Objective To analysis the expression of thyroid transcription factor 1 (TTF-1) in patients with lung adenocarcinoma, and discuss the relationship between TTF-1 expression and prognosis of patients with advanced lung adenocarcinoma. Methods A total of 786 cases of lung adenocarcinoma who were admitted to Xi'an Chest Hospital from January 2012 to June 2016 were selected. The expression of TTF-1 was detected by immunohistochemistry. The relationship between TTF-1 expression and patients ' clinicopathological features, treatment and survival were analyzed. Cox proportional hazard model was used to analyze the relationship between TTF-1 and prognosis of patients with advanced lung adenocarcinoma. Results Among 786 patients, 559 patients (71.12％) had positive TTF-1 expression, 227 patients (28.88％) had negative TTF-1 expression. The expression rates of TTF-1 in patients with well-differentiated, early stage, no lymph node metastasis, and no distant metastasis [77.26％ (197/255), 78.89％ (269/341), 78.95％ (225/285), and 75.61％(372/492)] were higher than those in patients with poorly differentiated, late stage, lymph node metastasis and distant metastasis 68.17％ (362/531), 65.17％ (290/445), 66.67％ (334/501), 63.60％ (187/294), the differenceswere statistically significant (χ 2 values were 6.917, 25.261, 13.339, and 12.911, all P < 0.05). The expressions of TTF-1 in primary lesions and metastatic lesions were consistent (κ = 0.894, P < 0.01). Among 385 patients with advanced lung adenocarcinoma who were unable to perform the operation, the proportion of epidermal growth factor receptor (EGFR) mutation in TTF-1 positive expression patients (45.60％, 109/239) was significantly higher than that in TTF-1 negative expression patients (26.02％, 38/146), and the difference was statistically significant (χ 2 = 14.721, P < 0.01). The median progression free survival (PFS) time of TTF-1 positive expression patients was significantly longer than that of TTF -1 negative expression patients (6.00 months vs. 4.20 months, P < 0.01), whether EGFR was mutation or not, the median PFS time of TTF-1 positive expression patients was significantly longer than that of TTF-1 negative expression patients (P =0.003; P < 0.01). TTF-1 expression (HR = 0.793, 95％ CI 0.639-0.984, P = 0.011) and EGFR gene status (HR =0.694, 95％ CI 0.432-0.864, P = 0.004) were independent influencing factors affecting the PFS of patients with advanced lung adenocarcinoma. Conclusions TTF-1 is widely expressed in lung adenocarcinoma and is associated with tumor differentiation, staging, lymph metastasis and distant metastasis. TTF-1 is a prognostic influencing factor in patients with advanced lung adenocarcinoma and can be used as a predictor of treatment for patients with advanced lung adenocarcinoma.

A study of spectrum of pulmonary pathology and expression of thyroid transcription factor-1 during neonatal period

Context: Neonatal period is the single most hazardous period of life. The major causes of neonatal death are prematurity and respiratory distress syndrome. We report a series of neonatal autopsies in our Neonatal Intensive Care Unit with special emphasis on pulmonary pathology. The spectrum of pathological changes in the lungs and thyroid transcription factor-1 (TTF-1) expression was studied in detail with reference to its spatial distribution. Aims: This study aims to analyze the causes of neonatal death with special attention to pulmonary pathology along with associated histopathological changes in lungs. We also evaluated the expression of TTF-1 at different levels of the airway. Materials and Methods: After taking consent and anthropometric measurements, autopsy was performed. Weights of all organs were taken, and histological sections were examined under hematoxylin and eosin stain. TTF-1 immunostaining was done on lung sections. Localization of TTF-1 was evaluated at the intrapulmonary level of terminal bronchioles (TBs), distal bronchioles, and alveoli. Results: We performed a series of 25 autopsies in neonates. In our series, most of the neonates were preterm (64%), had low birth weight (44%), and died within the first 7 days of life (80%). Majority (60%) of the neonates died due to pulmonary causes, followed by septicemia (24%), congenital anomalies (12%), and birth injury (4%). Among the respiratory causes, hyaline membrane disease (HMD) was diagnosed in maximum number of cases (32%), followed by pneumonia (12%) and pulmonary hemorrhage (12%). The TTF-1 expression in TBs, distal airways, and alveoli was significantly reduced or absent in cases of HMD compared to the control group. Conclusions: In this study, we observed that HMD is the most common cause of perinatal death among respiratory disorders, and in this disease, the expression of TTF-1 is significantly reduced in TBs, distal airways, and alveoli compared to the control group.

Low‑grade papillary adenocarcinoma of nasopharynx with expression of thyroid transcription factor‑1: Case report and review of literature.

Low‑grade papillary adenocarcinomas with expression of thyroid transcription factor‑1 (TTF‑1) are rare tumors of the nasopharynx, with only a few cases reported in the literature. These tumors have an excellent prognosis following complete surgical excision. We report a 13‑year‑old boy with this rare tumor in the nasopharynx. The patient underwent complete surgical excision of the tumor and was on follow‑up without evidence of recurrence.

The heredity of research in neonatal respiratory distress syndrome / 中国小儿急救医学

Neonatal respiratory distress syndrome(NRDS)is the most critical disease in neonatal pe-riod.Studies have proved that genetic factors play an important role in the pathogenesis of NRDS.More and more proteins and genes which are associated with NRDS are researched.This article mainly reviewed the re-search of surfactant protein,ATP-binding cassette transporters A3,mannose-binding lectin,thyroid transcrip-tion factor-1and NRDS.

Dual surrogate markers for rapid prediction of epidermal growth factor receptor mutation status in advanced adenocarcinoma of the lung: A novel approach in resource‑limited setting.

INTRODUCTION: Tyrosine kinase inhibitors have revolutionized the treatment of metastatic lung cancer in patients with epidermal growth factor receptor (EGFR) mutations. Amplified refractory mutation system (ARMS)‑reverse transcription‑polymerase chain reaction (RT‑PCR), the current standard for detecting EGFR mutation status is time‑consuming and highly expensive. Consequently any surrogate test which are cheaper, faster and as accurate as the PCR method will help in early diagnosis and management of patients with lung cancer, especially in resource‑limited settings. MATERIALS AND METHODS: Eighty‑five patients, all of South Indian origin, with adenocarcinoma of lung, registered between October 2009 and January 2013, were evaluated for EGFR mutation status by using scorpion probe based ARMS RT‑PCR method. Immunohistochemical (IHC) was performed using the phosphorylated AKT (P‑AKT) and thyroid transcription factor‑1 (TTF‑1) on above patient’s sample, and the results were compared with EGFR mutation tests. RESULTS: EGFR mutation was positive in 34 of 85 patients (40%). P‑AKT and TTF‑1 were positive in 50 (58.8%) and 68 (80%) patients respectively. Both P‑AKT and TTF‑1 had statistically significant correlation with EGFR mutation status. Positive and negative predictive value of P‑AKT in diagnosing EGFR mutation was 58% and 85.5% and that for TTF‑1 was 48.5% and 94.1%, respectively. The problem of low positive predictive value can partly be overcome by testing P‑AKT and TTF‑1 simultaneously. CONCLUSION: P‑AKT and TTF‑1 using IHC had statistically significant correlation with EGFR mutation with high negative predictive value. In the case of urgency of starting treatment, EGFR mutation testing may be avoided in those patients who are negative for these IHC markers and can be started on chemotherapy.

Expression and significance of TTF-1 and CgA in small cell lung carcinoma / 国际肿瘤学杂志

Objective To investigate the expression and clinical significance of thyroid transcription factor-1(TTF-1)and chromogranin A(CgA)in small cell lung cancer(SCLC). Methods The expressions of TTF-1 and CgA protein in 68 cases of SCLC tissues and 20 cases of normal lung tissues were examined by immunohistochemistry method,and their correlations with clinical features of SCLC were analyzed. Results The positive rates of TTF-1 and CgA protein in SCLC were 88. 2%(60 / 68)and 70. 6%(48 / 68),respec-tively,and they were higher than those in normal lung tissue[10. 0%(2 / 20)and 5. 0%(1 / 20);χ2 = 45. 442, P = 0. 000;χ2 = 26. 941,P = 0. 000]. The expression of TTF-1 protein was not related to the patients' age,sex and tumor size,while closely related to smoking index(χ2 = 4. 131,P = 0. 042),lymph node metastasis(χ2 =5. 488,P = 0. 019)and clinical stage(χ2 = 6. 011,P = 0. 014). The expression of CgA protein was not related to the patients' age,sex,tumor size and smoking index,while closely related to lymph node metastasis(χ2 =9. 895,P = 0. 002)and clinical stage(χ2 = 4. 145,P = 0. 042). Conclusion TTF-1 and CgA protein are highly expressed in SCLC,especially in the patients with lymph node metastasis and extensive disease.

Application value of cell keratin 7 ,thyroid transcription factor-1,Napsin A,cell keratin5/6,p40 and p63 immunohistochemical stains in lung adenocarcinoma and squamous cell carcinoma / 中国综合临床

Objective To study the significant immunohistochemical marker to identify lung adenocarcinoma(ADC) and squamous cell carcinoma(SCC).Methods Three hundred and twenty-nine Choose 329 cases of nonsmall-cell lung cancer (NSCLC) were chosen.Analysis of the clinical and pathological features.The expression of cell keratin 7 (CK7),thyroid transcription factor-1 (TTF-1),Napsin A,CK5/6,p40 and p63 were detected by using immunohistochemistry.Results (1) Among 329 specimens,containing 129 cases of resections,195 cases of biopsies and 5 cases of pleural effusion specimens.(2)In these cases,187 cases were classified to be ADC,142 cases were classified to be SCC.(3) CK7,TTF-1,Napsin A,CK5/6,p40,p63 sensitivity were 97.9％,87.2％,81.3％,6.4％,3.7％,18.7％ in ADC groups,and 25.4％,11.3％,0,92.3％,95.1％,98.6％ in SCC groups,and the differences of two groups were significant statistically (x2 =190.665,187.432,214.542,242.003,274.407,206.818;P＜ 0.001).(4) In the 3 IHC of ADC,CK7 had the highest sensitivity,Napsin A had the highest specificity.In the 3 IHC of SCC,p63 had the highest sensitivity,p40 had the highest specificity.Conclusion CK7,TTF-1,Napsin A,CK5/6,p40 and p63 can be a markable panel of immunohistochemistry in the differential diagnosis of NSCLC.

Immunohistochemical characteristics and prognosis study of 90 small cell lung cancer patients / 临床与实验病理学杂志

Purpose To explore the immunohistochemical features of neuroendocrine markers, CKpan and TTF-1 and their relationship to TNM stage and prognosis in small cell lung cancer (SCLC). Methods The expression of NSE, CgA, Syn, CD56, TTF-1 and CK-pan in SCLC tissue specimens were detected using immunohistochemical EnVision indirect method. Clinical data and TNM stage of 90 patients were collected and the overall survival ( OS) was followed up by telephone. Results Of 90 cases of SCLC, the vast majority were occured in the elderly men. The ratio of man to woman was 5 to 1. The median age was 64 years old. The stageⅠ+Ⅱ was 21 cases, 30 in stageⅢand 39 cases in stage IV. The positive rate of immunohistochemical staining of neuroendocrine markers for NSE, CgA, Syn and CD56 were 83. 3%, 70%, 65. 5% and 86%, respectively. The positive rate of CKpan, TTF-1 were 92. 2% and 81. 1%. Kaplan-Meier analysis indicated that the expression of TTF-1 and NSE were significantly correlated with the TNM stage and over-all survival of patients with SCLC (P<0. 05). The median OS was 8 months in positive expression of TTF-1, which was higher than those in negative expression of TTF1 (5. 5 months)(P=0. 000). The median OS was 7 months in NSE positive expression which was lower than those in negative expression of NSE (11 months)(P=0. 009). The median OS of stageⅠ+Ⅱ,ⅢandⅣwere 16 months, 9 months and 4 months with significant difference ( P=0. 000 ) . Cox multivariate analysis indicated the TTF-1 expression and TNM were independent prognostic factors for the OS of the SCLC patients. Conclusion Most of SCLC has neuroendocrine differentiation, expression CKpan and TTF-1. The expression of TTF-1 may be negative correlation but NSE positive correlation with the prognosis of SCLC patients. And the TTF-1 expression and TNM may be independent prognostic factors for the OS of the SCLC patients.

Cutaneous Metastasis from Small Cell Lung Cancer Expressing Thyroid Transcription Factor-1 / 대한피부과학회지

No abstract available.

Prostatic Cancer Presenting as an Isolated Large Lung Mass / 결핵및호흡기질환

A hidden primary tumor presenting as an isolated lung mass is a diagnostic challenge to physicians because the diagnosis of lung cancer is likely to be made if the histologic findings are not inconsistent with lung cancer. A large lung mass was found incidentally in a 59-year-old man. Although adenocarcinoma was diagnosed by percutaneous needle biopsy, thyroid transcription factor-1 (TTF-1) immunostaining was negative, raising suspicion that there was another primary site. There was no abnormal finding except for the lung mass on a 18FDG-PET/CT scan and the patient did not complain of any discomfort. Finally, prostatic cancer was confirmed through the study of tumor markers and prostate-specific antigen (PSA) immunostaining. Because of the rare presentation of a single lung mass in malignancies that have another primary site, physicians should carefully review all data before making a final diagnosis of lung cancer.

Uterine Cervical Large Cell Neuroendocrine Carcinoma Concurrent with High Grade Squamous Intraepithelial Neoplasia: A Case Report

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare and aggressive malignancy. We report a case of uterine cervical LCNEC concurrent with high grade squamous intraepithelial neoplasia (HG-SIN). The LCNEC expressed chromogranin A and thyroid transcription factor 1 (TTF1). The HG-SIN was negative for these markers. Human papillomavirus (HPV) type 18 was positive in LCNEC whereas both type 16 and 18 were positive in HG-SIN by nested polymerase chain reaction. This case showed TTF1 positivity nonetheless diagnosed as a primary uterine cervical LCNEC confirmed by the detection of HPV genome within the tumor. It is critical to recognize LCNEC of the uterine cervix even in the small biopsy specimen because it is a distinctive clinicopathological entity with highly aggressive behavior and unfavorable outcome.

A Case of Merkel Cell Carcinoma Differentially Diagnosed by Thyroid Transcription Factor-1 / 대한피부과학회지

Merkel cell carcinoma is a rare aggressive primary neuroendocrine skin tumor. It is more prevalent in elderly patients and commonly occurs as a solitary lesion on the head and neck. This case reports an 84-year old female with an asymptomatic 1x1.5 cm sized erythematous nodule on the right side of the nose that had rapidly enlarged over a one-month period. Histopathologically, it is difficult to differentiate Merkel cell carcinoma from metastatic small cell lung cancer. Thyroid transcription factor-1 (TTF-1) staining was very useful to differentiate Merkel cell carcinoma from metastatic small cell lung cancer. This case was positive for cytokeratin 20, but negative for TTF-1. We report a case that was diagnosed as Merkel cell carcinoma by TTF-1 staining.

Expression of thyroid transcription factor-1 in hepatocellular carcinoma / 上海第二医科大学学报

Objective To investigate the value of thyroid transcription factor-1(TTF-1) in the diagnosis and biological behavior assessment of hepatocellular carcinoma (HCC). Methods Thirty liver specimens obtained from benign lesions were analysed, among which 25 were hepatic cirrhosis and inflammatory diseases, and the other 5 were adenomas. And there were 176 specimens of liver tumors, among which 142 were HCC (well differentiated, n=12; moderately differentiated, n=57; poorly differentiated, n=73), 17 were intrahepatic cholangiocellular carcinoma (ICC) and the other 17 were liver metastatic carcinoma (MC). The expression of TTF-1 was examined immunohistochemically in the above tissues, and the difference in expression of TTF-1 among different tissues was examined by Fisher's exact test, Kruskal-Wallis test and Spearman rank correlation analysis. Results TTF-1 was significantly expressed in the cytoplasms of all the hepatocytes besides tumors and liver benign lesions. The expression rate of TTF-1 in HCC was 78.9% (112/142), however, TTF-1 was negatively expressed in ICC and MC(P

Thyroid Transcription Factor-1 (TTF-1) Expression in Human Lung Carcinomas: Its Prognostic Implication and Relationship with Expressions of p53 and Ki-67 Proteins

This study was aimed to evaluate the prevalence and prognostic implication of thyroid transcription factor-1 (TTF-1) immunoreactivity in 81 human lung carcinomas, including 65 cases of non-small cell lung carcinoma (NSCLC) and 16 cases of small cell lung carcinoma (SCLC); and also to investigate its relationship with the cell proliferation and regulation by immunostaining of Ki-67 and p53 proteins, respectively. The immunohistochemical staining for TTF-1(clone 8G7G3/1) was performed and several clinicopathologic variables and the follow-up data were obtained. The immuno-staining results for TTF-1 were semiquantitatively interpreted as negative and positive. Of NSCLCs, TTF-1 is highly expressed in adenocarcinomas (76%), whereas squamous cell carcinomas revealed no immunoreactivity (0%). SCLCs showed strong TTF-1 expression (88%). In NSCLC, TTF-1 expression was inversely correlated with Ki-67 proliferative activity and independent of p53 overexpression. TTF-1(+) group tended to show better survival than TTF-1(-) group in NSCLC. 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.

Expression of Thyroid Transcription Factor-1 and Ki-67 in the Thyroid Neoplasms

PURPOSE: Thyroid transcription factor-1 (TTF-1) has been known to regulate the transcriptional activity of thyroid-specific genes. Ki-67 has been known as a marker for indicating tumor growth. This study was designed to campare the expressions of TTF-1 and Ki-67 on non- neoplastic and neoplastic thyroid tissues. METHODS: The surgically resected specimens of various histological types of thyroid tumor, from the files of the Dept. of surgery, Chung-Ang University Pil-Dong Hospital, between January 1998 and June 2002 were reviewed, and 55 cases selected for immunohistochemical studies. The materials consisted of tissues from 10 nodular hyperplasias, 28 papillary carcinomas, 15 follicular adenomas and 12 follicular carcinomas. All specimens were routinely processed, and paraffin blocks were available in all cases. Immunohistochemical stains for TTF-1 and Ki-67 were also performed. RESULTS: In all the cases, including the nodular hyperplasias, papillary carcinomas, follicular adenomas and follicular carcinomas, expressions of the TTF-1 were observed. The properties of the TTF-1 expression, including staining intensity, extent and index were not related to the tumor type. The expression of TTF-1 was inversely correlated with the tumor proliferation fraction, as assessed by the Ki-67 staining index. CONCLUSION: TTF-1 was expressed in almost all the benign lesions and well differentiated carcinomas, and correlated with the tumor proliferation fraction.

Effect of Class 2 Transactivator on Expression of Thyroid Transcription Factor-1 in FRTL-5 Cells / 대한내분비학회지

BACKGROUND: Gamma-interferon (gamma-IFN) is known to suppress thyroperoxidase (TPO), thyroglobulin (Tg), thyrotropin receptor (TSHR) mRNA expression via unclarified mechanism. Thyroid transcription factor-1 (TTF-1) is a nuclear protein involved in the maximal expression and tissue specific expression of thyroid-specific antigens (TPO, Tg, TSHR, NIS) in thyrocytes. Although It's plausible that gamam-IFN induced suppression of thyroid-specific antigen expression may be mediated by decrease of TTF-1 expression, such an effect has not been documented yet. In this study we investigated the effect of gamma-IFN on the expression of TTF-1 in the rat thyroid cell, FRTL-5, and determined whether such an effect is mediated by sclass 2 transactivator (CIITA). METHEODS: The mRNA expression of TTF-1 was quantitated by northern blot analysis after treatment of gamma-IFN, and after expression of CIITA in FRTL-5 cells. Four different promoter constructs were made by cloning into the pRSV-luciferase vector, each contained 5'flanking sequence of different lengths (-5.18 kb, -4.11 kb, -1.94 kb, -1.15 kb) of rat TTF-1 gene. Effects of gamma-IFN and CIITA on promoter activities were analyzed by luciferase assay in FRTL-5 cells into which each promoter construct had been transfected by DEAE-dextran method. RESULTS: Steady state TTF-1 mRNA level at 48 h after gamma-IFN treatment (100 U/mL) was significantly decreased from that of the pre-treatment level (1.65+/-0.16 vs. unit, p<0.05). In all 4 promoter constructs gamma-IFN significantly suppressed promoter activities compared to the vector only transfected cells. CIITA expression in FRTL-5 cells significantly decreased the steady state TTF-1 mRNA level when compared to that in mock-transfected cells (1.69+/-0.31 vs. 1.17+/-0.44 arbitrary unit, p<0.05). CIITA expression in FRTL-5 cells caused suppression of promoter activities in -5.18 kb and -4.11 kb constructs, but had no effects on those activities in -1.94 kb; and -1.15 kb constructs. CONCLUSION: gamma-IFN, directly and indirectly via CIITA expression, suppressed the transcription of TTF-1 gene in the FRTL-5 cells. It may be one of the mechanisms involved in the gamma-IFN-induced suppression of thyroid-specific protein expressions in thyrocytes 1.25+/-0.27 arbitrary

Expressions of TTF-1,MHC-1 in thyroid of autoimmune thyroid diseases / 中华内分泌代谢杂志

Expression of major histocompatibility complex class 1(MHC-1)and thyroid specific transcription factor-1(TTF-1)in thyroid follicular epithelia of Graves'disease and Hashimoto's thyroiditis measured by immunohistochemistry technique were all significantly increased as compared with those in normal controls,suggesting that TTF-1 and MHC-1 seem to contribute to the development of autoimmune thyroid diseases.