Histopathological and immunohistochemical characteristic for lung cancer among Mongolian patients / Шинэ санаа Шинэ нээлт

Background@#Lung cancer is the leading cause of cancer death in both men and women. In the past decade, histopathological classification of lung cancer has become increasingly important in selecting the appropriate treatment.@*Methods@#All cases of lung cancer diagnosed pathologically in the last 2.5-year period were retrospectively identified at National Cancer Center and performed by descriptive case series design.@*Results@#The average age of our participants was 62, of which 82.2% were men. A total of 214 cases of lung cancer were reported, including 142 (66.4%) squamous cell carcinoma (SCC), 34 (16%) adenocarcinoma (AC), 4 (1.7%) NSCLC, 29 (13.6%) small cell carcinoma (SmCC) and 5 (2.3%) cases of other/unspecified type. Based on only morphology, initially 32 (17.7%) cases of NSCLC were diagnosed, whereas after immunohistochemistry (TTF-1 or NAPA positive/p63 negative, and vice versa) staining, this category reduced to 2.2%.@*Conclusions@#Among both males and females, SCC which is highly related to smoking was the most common histologic type of lung cancer. Our results showed that an approach of using only a two-antibody panel (p63 and TTF-1) might help in the reduction of diagnostic category of NSCLC-NOS significantly.

Expression and clinical significance of CK5/6, DSG3, P40, TTF-1, CK7, NapsinA in small biopsy specimens of non-small cell lung cancer / 中国基层医药

Objective@#To detect the expression and the differential significance of CK5/6, DSG3, P40, TTF-1, CK7, NapsinA in small biopsy specimens of non-small cell lung cancer (NSCLC), squamous cell carcinoma (SCC) and adenocarcinoma (AC).@*Methods@#Immunohistochemical SP method was used to detect the expressions of CK5/6, DSG3, P40, TTF-1, CK7 and NapsinA in 120 small biopsy specimens of NSCLC hospitalized in the Central People's Hospital of Tengzhou from January 2016 to December 2017, and the results were analyzed combined with the clinical characteristics of NSCLC.@*Results@#The positive expression rates of CK5/6, DSG3 and P40 in lung SCC were 100.0%(56/56), 89.3%(50/56) and 96.4%(54/56), respectively, with specificity of 90.6%, 100.0% and 100.0%, respectively.The positive expression rates of NapsinA, TTF-1 and CK7 in lung AC were 81.3%(52/64), 90.6%(58/64) and 93.8%(60/64), respectively, with specificity of 100.0%, 92.9% and 96.4%, respectively.The positive expression rates of CK5/6, DSG3, P40 in SCC had statistically significant differences compared with those in AC (all P<0.05), and the expression of TTF-1, CK7 and NapsinA in AC had statistically significant differences compared with those in SCC (all P<0.05).@*Conclusion@#CK5/6, DSG3, P40, TTF-1, CK7 and NapsinA are of great significance in the differential diagnosis of SCC and AC in small biopsy specimens of NSCLC.

Analysis of Correlation between TTF-1 and Sensitivity to First-line Chemotherapy and Prognosis in Patients with Small Cell Lung Cancer / 中国肺癌杂志

BACKGROUND@#Thyroid transcription factor-1 (TTF-1) has been widely studied in non-small cell lung cancer, which is considered as an independent prognostic factor in patiens with non-small cell lung cancer. However, there are few studies on the prognostic value of TTF-1 in small cell lung cancer (SCLC). The purpose of this study was to explore the relationship between the expression state of TTF-1 and the sensitivity to first-line chemotherapy and prognosis in patients with SCLC.@*METHODS@#A retrospective analysis was made on 234 patients with SCLC who were diagnosed and treated in The Affiliated Hospital of Qingdao University and received platinum-based chemotherapy. The clinical characteristics, treatment and survival of the patients were followed up. Chi χ² test and Logistic regression model were used to analyze the relationship between TTF-1 expression and chemotherapy response rate. Kaplan-Meier method and Cox proportional hazard regression model were used to analyze the effect of TTF-1 expression on survival time of patients.@*RESULTS@#Among the 234 patients, the positive expression of TTF-1 was 188 cases (80.3%), and the negative expression of TTF-1 was 46 cases (19.7%). The objective response rate (ORR) of first-line chemotherapy in patients with positive expression of TTF-1 was higher than that in patients with negative expression of TTF-1 (70.7% vs 47.8%) (χ²=8.681, P=0.003). Logistic regression multivariate analysis showed that the expression state of TTF-1 was an independent predictor of ORR in first-line chemotherapy (OR=0.216, 95%CI: 0.076-0.615, P=0.004), however this difference was only reflected in LS-SCLC. The median progression free survival (PFS) of patients with negative expression of TTF-1 was shorter than that of patients with positive expression (6.9 months vs 9.0 months) (χ²=9.357, P=0.002). The median OS in TTF-1 negative group was shorter than that in TTF-1 positive group (13.3 months vs 20.1 months)(χ²=12.082, P=0.001).@*CONCLUSIONS@#TTF-1 expression is an independent predictor of first-line chemotherapy response rate and survival in patients with SCLC, and may become a biomarker to predict the efficacy and prognosis of SCLC.

Expression and clinical significance of CK5／6,DSG3,P40,TTF-1,CK7,NapsinA in small biopsy specimens of non-small cell lung cancer / 中国基层医药

Objective To detect the expression and the differential significance of CK 5／6,DSG3,P40,TTF-1,CK7,NapsinA in small biopsy specimens of non -small cell lung cancer ( NSCLC),squamous cell carcinoma (SCC) and adenocarcinoma (AC).Methods Immunohistochemical SP method was used to detect the expressions of CK5／6,DSG3,P40,TTF-1,CK7 and NapsinA in 120 small biopsy specimens of NSCLC hospitalized in the Central People's Hospital of Tengzhou from January 2016 to December 2017,and the results were analyzed combined with the clinical characteristics of NSCLC.Results The positive expression rates of CK5／6,DSG3 and P40 in lung SCC were 100.0%(56／56),89.3%(50／56) and 96.4%(54／56), respectively,with specificity of 90.6%,100.0% and 100.0%,respectively.The positive expression rates of NapsinA ,TTF-1 and CK7 in lung AC were 81.3%(52／64), 90.6%(58／64) and 93.8%(60／64),respectively,with specificity of 100.0%,92.9% and 96.4%,respectively. The positive expression rates of CK5／6,DSG3,P40 in SCC had statistically significant differences compared with those in AC (all P＜0.05),and the expression of TTF -1,CK7 and NapsinA in AC had statistically significant differences compared with those in SCC ( all P＜0.05).Conclusion CK5／6,DSG3,P40,TTF-1,CK7 and NapsinA are of great significance in the differential diagnosis of SCC and AC in small biopsy specimens of NSCLC .

Immunocytochemistry Study on Pulmonary Cytology Samples in Lung Cancer

There is an increasing need to subtype non-small cell lung carcinoma (NSCLC) into squamous cell carcinoma and adenocarcinoma of lung, and this subtyping guides the treatment with the advent of targeted therapies that are available for cases of adenocarcinoma of lung, by which prognosis can be improved. In cases of lung cancer, many a times, cytology may be the only material available to render a diagnosis; cases that are poorly differentiated on morphology are challenging to subtype and the immunocytochemical markers can be applied on these cytosmears for further subtyping of NSCLC. Aims and Objectives This study was carried out to check the expression of p63 and TTF-1 in diagnostically difficult cases, such as NSCLC, poorly differentiated lung carcinomas on pulmonary cytology samples, and to further subtype them into squamous cell and adenocarcinoma. Materials and Methods The study period was from 1 September 2013 to 31 August 2015; during this span, the total number of malignancies that were diagnosed on cytology was 585 cases. Prestained slides (haematoxylin and eosin or H&E, Papanicolaou or Pap) were collected over a span of these two years and these were destained using 1% acid alcohol with intermittent washing followed by running of p63 and TTF-1 as the immunocytochemical markers. Observations and Results The smears that are positive for p63 are labelled as squamous cell carcinoma and those that are positive for TTF-1 are labelled as adenocarcinoma, as these markers are highly sensitive and specific for the diagnosis of squamous cell and adenocarcinoma, respectively; neuroendocrine markers were used in the cases that were positive for TTF-1 to rule out small cell carcinoma. Conclusion: By the positive expression of p63 and TTF-1, the cases were labelled as squamous cell carcinoma and primary adenocarcinoma of lung, with due considerations given to the clinical and radiological parameters.

Expression of TTF1 in hypothalamus of female rats and its relationship with GnRH and KiSS1 / 上海交通大学学报（医学版）

Objective·To investigate the changes and distribution of thyroid transcription factor-1 (TTF1) expression around the puberty and to explore the position relationship among gonadotropin-releasing hormone (GnRH), KiSS1 and TTF1 expression in the hypothalamus of female SD rats. Methods?·?Female SD rats were divided into three groups: juvenile (JUV), early puberty (EP), and adult (AD). Tissue immunofluorescence staining was used to detect the expression of TTF1, KiSS1 and GnRH immunoreactive cells in the hypothalamus and the relative position among them. Real-time PCR was used to measure the expression of KiSS1, GnRH, TTF1 on mRNA levels in the hypothalamus, anteroventral periventricular nucleus (AVPV), and arcuate nucleus (ARC) respectively. Western blotting was performed to detect the changes in protein level of KiSS1 and TTF1. Results?·?TTF1 was densely expressed in hypothalamus nucleus AVPV, ARC and median eminence (ME) of female rats. GnRH,KiSS1 and TTF1 were adjacently expressed in ARC and ME. The mRNA level of TTF1 in the hypothalamus showed an upward trend after a slight decrease, while in AVPV and ARC tended to be consistent and showed an upward trend. The GnRH mRNA expression levels were significantly increased and reached the peak at AD. The mRNA expression levels of KiSS1 showed a sharp rise which was prior to the peak expression of GnRH mRNA at EP and then sustained the high level until AD. The protein expression level of TTF1 reached the peak at AD and the KiSS1 expression showed a sustained growth. Both of them showed an upward trend and basically consistent with the mRNA expression trend. Conclusion?·?Neuronal nuclei protein TTF1 mainly expressed in the nuclei AVPV, ARC, and ME of female rat hypothalamus. It was prominent in cells of ARC and ME which were localized GnRH, KiSS1, TTF1 positive neural cells. During the development of puberty onset, KiSS1 mRNA preceded GnRH mRNA to reach the peak at EP. The expression of TTF1 mRNA increased and reached a peak at AD, which was consistent with the overall increase of KiSS1 and GnRH expression. Protein expression of KiSS1 showed a corresponding upward trend together with their mRNA expression. TTF1 protein expression increased and peaked in AD.

Lung cancer biopsy: Can diagnosis be changed after immunohistochemistry when the H&E-Based morphology corresponds to a specific tumor subtype?

OBJECTIVES: Advancements in non-small cell lung cancer treatment based on targeted therapies have made the differentiation between adenocarcinoma and squamous cell carcinoma increasingly important. Pathologists are challenged to make the correct diagnosis in small specimens. We studied the accuracy of an immunohistochemical panel in subclassifying non-small cell lung cancer in routine small biopsies and compared the results with the diagnosis from resected lung specimens, autopsy samples or biopsied/resected metastases. METHODS: In total, 340 lung cancer biopsies were investigated for the expression of CK5, TTF1, p63 and surfactant. RESULTS: We characterized 166 adenocarcinomas and 124 squamous cell carcinomas. Overall, 85% of cases displayed binary staining (TTF1 positive/p63 negative, and vice versa). The diagnoses of ten cases with a morphology that indicated a specific tumor subtype were changed after immunohistochemistry (IHC). A second specimen was available for 71 patients, and the first diagnosis at biopsy was confirmed in 95% of these cases. Most non-small cell lung cancer cases present a binary immunohistochemical profile in small biopsies, contributing to good diagnostic accuracy with routine markers. In a small proportion of cases, the diagnosis can be changed after IHC even when the morphological aspects indicate one specific tumor subtype. CONCLUSIONS: We recommend that routine small biopsies of lung cancer without classic morphology should be subjected to a minimum immunohistochemical panel to differentiate adenocarcinoma from squamous cell carcinoma.

Expression of TTF1 in hypothalamus of female rats and its relationship with GnRH and KiSS1 / 上海交通大学学报（医学版）

Objective • To investigate the changes and distribution of thyroid transcription factor-1 (TTF1) expression around the puberty and to explore the position relationship among gonadotropin-releasing hormone (GnRH), KiSS1 and TTF1 expression in the hypothalamus of female SD rats. Methods • Female SD rats were divided into three groups: juvenile (JUV), early puberty (EP), and adult (AD). Tissue immunofluorescence staining was used to detect the expression of TTF1, KiSS1 and GnRH immunoreactive cells in the hypothalamus and the relative position among them. Real-time PCR was used to measure the expression of KiSS1, GnRH, TTF1 on mRNA levels in the hypothalamus, anteroventral periventricular nucleus (AVPV), and arcuate nucleus (ARC) respectively. Western blotting was performed to detect the changes in protein level of KiSS1 and TTF1. Results • TTF1 was densely expressed in hypothalamus nucleus AVPV, ARC and median eminence (ME) of female rats. GnRH,KiSS1 and TTF1 were adjacently expressed in ARC and ME. The mRNA level of TTF1 in the hypothalamus showed an upward trend after a slight decrease, while in AVPV and ARC tended to be consistent and showed an upward trend. The GnRH mRNA expression levels were significantly increased and reached the peak at AD. The mRNA expression levels of KiSS1 showed a sharp rise which was prior to the peak expression of GnRH mRNA at EP and then sustained the high level until AD. The protein expression level of TTF1 reached the peak at AD and the KiSS1 expression showed a sustained growth. Both of them showed an upward trend and basically consistent with the mRNA expression trend. Conclusion • Neuronal nuclei protein TTF1 mainly expressed in the nuclei AVPV, ARC, and ME of female rat hypothalamus. It was prominent in cells of ARC and ME which were localized GnRH, KiSS1, TTF1 positive neural cells. During the development of puberty onset, KiSS1 mRNA preceded GnRH mRNA to reach the peak at EP. The expression of TTF1 mRNA increased and reached a peak at AD, which was consistent with the overall increase of KiSS1 and GnRH expression. Protein expression of KiSS1 showed a corresponding upward trend together with their mRNA expression. TTF1 protein expression increased and peaked in AD.

Cutaneous Metastasis of Small Cell Lung Cancer Masquerading as Lipomatosis / 대한피부과학회지

No abstract available.

Metastatic Common Bile Duct Cancer from Pulmonary Adenocarcinoma Presenting as Obstructive Jaundice / 대한소화기학회지

We report an extremely rare case of metastatic common bile duct cancer from pulmonary adenocarcinoma presenting as obstructive jaundice. The patient was a 76-year-old male, who presented with generalized weakness and right upper quadrant pain. Plain chest X-ray noted multiple small nodules in both lung fields. Abdominal computed tomography scan showed a stricture of the mid common bile duct along with ductal wall enhancement. Endoscopic retrograde cholangiography revealed a concentric, abrupt narrowing of the mid-common bile duct suggestive of primary bile duct cancer. However, pathology comfirmed metastatic common bile duct cancer arising from pulmonary adenocarcinoma with immunohistochemical study with thyroid transcriptional factor-1 (TTF-1).

Expression and prognostic value of TTF-1 of stage Ⅰ non-small cell lung cancer / 中华胸心血管外科杂志

Objective To study the expression and clinical significance of thyroid transcription factor-1 (TTF-1) in stage Ⅰ non-small cell lung cancer (NSCLC) after operation and to 1 investigate the values in identification of the prognosis of stage Ⅰ NSCLC.Methods The expression of TTF-1 in 129 specimens of stage Ⅰ NSCLC was detected by immunohistochemistry.Results The positive rate of TTF-1 in stage Ⅰ NSCLC was 64.3％.There were significant differences in TTF-1 expression rate among pathological subtypes (x2 =25.231,P ＜ 0.001),different ages (x2 =4.581,P =0.032),sex (x2 =4.900,P =0.027) and differentiation degrees(x2 =11.519,P =0.019).Univariate analysis suggested that in the stage Ⅰ NSCLC patients,the median disease-free survival and overall survival of those positive for TTF-1 expression were superior to those negative:38.9 months versus 27.8 months (P =0.023) and 64.10 months versus 50.68months (P =0.013).Cox regression analysis suggested that TTF-1 expression,tumor differentiation degrees were independent factors affecting the prognosis of stage Ⅰ NSCLC.Conclusion Patients with TTF-1 positive expression often had better survival.Positive expression of TTF-1 and differentiation degree of tumor were independent prognostic factors to affect the prognosis of NSCLC.

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

No abstract available.

Transcriptional activity of the 5'-flanking region of the thyroid transcription factor-1 gene in human thyroid cell lines

Thyroid transcription factor-1 (TTF-1, NKX2-1) is a homeodomain-containing transcriptional factor that binds to and activates the promoters of thyroid and lung-specific genes, such as thyroglobulin, thyroid peroxidase, and thyroid stimulating hormone receptor. TTF-1 is known to play a key role in the development of the thyroid. However, the precise mechanism of TTF-1 gene transcription in human thyroid cells has not been studied. The expression of transcriptional activity in various lengths of the 5'-flanking region of the human TTF -1 gene was studied in TTF-1 positive and negative human thyroid cell lines. Increased transcriptional activity was observed in thyroid cell lines containing plasmids that coded for a sequence proximal to the transcription start site of exon 1 of the TTF-1 gene. However, we did not observe any difference in promoter activity in the region up to -2.6 kb from the proximal transcription start site of the TTF-1 gene between TTF-1 positive and negative cells. These results suggest that the proximal 5'-flanking region of the human TTF -1 gene does not contain sufficient cis-active regulatory information to direct gene expression in thyroid cells,and that other cis-or trans-acting factors participate in the thyroid specific gene expression of TTF-1.

Estudo dos genes TTF-1 e EAP1 em pacientes com distúrbios puberais centrais e avaliação neurológica e neurocognitiva de pacientes com hamartoma hipotalâmico / Analysis of TTF-1 and EAP1 genes in patients with central pubertal disorders and neurologic and neurocognitive evaluation of patients with hypothalamic hamartoma

O mecanismo de controle da secreção de GnRH inclui diversas vias neuronais. Estudos em modelos animais identificaram genes que codificam fatores de transcrição, tais como TTF-1 (thyroid transcription factor 1) e EAP1 (enhanced at puberty), que atuam no controle transcricional de genes codificadores de fatores excitatórios (KiSS1 e GnRH) e inibitórios (preproencefalinas) regulando a secreção de GnRH. Em primatas, a expressão de EAP1 e TTF-1 aumenta, no início da puberdade, nas regiões hipotalâmicas envolvidas na secreção de GnRH. Nos modelos animais, a deleção pós-natal de TTF-1 e o silenciamento do EAP1 provocam atraso puberal e prejuízo na função reprodutiva. TTF-1 também está envolvido na morfogênese diencefálica, por meio da via de sinalização da família Sonic-Hedgehog. Anormalidades na secreção de GnRH resultam em distúrbios puberais, que variam de puberdade precoce central (PPC) a hipogonadismo hipogonadotrófico. Hipotetizamos que anormalidades genéticas no TTF-1 e EAP1 estejam envolvidas na patogênese dos distúrbios puberais centrais. A PPC pode ser idiopática ou devido a causas orgânicas, sendo o hamartoma hipotalâmico, uma malformação congênita não neoplásica, a mais conhecida. Os pacientes com PPC devido a hamartoma hipotalâmico podem cursar com alterações neurológicas e cognitivas. Nossos objetivos foram: estudar as regiões codificadora do TTF-1 e do EAP1 e a região promotora do TTF-1 em pacientes com distúrbios puberais centrais; estabelecer a prevalência, taxa de penetrância e modo de herança da forma familial de PPC e caracterizar as manifestações neurológicas e neurocognitivas de pacientes com PPC devido a hamartoma hipotalâmico. Foram selecionados 133 pacientes com distúrbios puberais centrais - PPC idiopática (n=71), PPC devido a hamartoma hipotalâmico (n=15) e hipogonadismo hipogonadotrópico isolado normósmico (HHIn) (n=47) - e controles (n=53). Os genes TTF-1 e EAP1 foram amplificados e submetidos a sequenciamento automático. Os tratos...

GnRH secretion control involves multiple neuronal pathways. Animal studies have identified genes which codifies transcription factors, such as TTF-1 (thyroid transcription factor 1) and EAP1 (enhanced at puberty), that act in the transcriptional control of genes that codifies excitatory (KiSS1 and GnRH) and inhibitory factors (preproenkephalines) regulating GnRH secretion. In nonhuman primates, expression of EAP1 and TTF-1 are increased at the hypothalamic regions involved in GnRH secretion, at the beginning of puberty. In animal models, post-natal TTF-1 deletion and silencing of EAP1 lead to pubertal delay and damage of reproductive function. TTF-1 is also involved in diencephalic morphogenesis, through signalization via Sonic-Hedgehog family. Abnormalities in GnRH secretion are responsible for pubertal disorders, varying from central precocious puberty (CPP) to hypogonadotropic hypogonadism. We hypothesized that genetic anomalies at TTF-1 and EAP1 are involved in the pathogenesis of central pubertal disorders. CPP may be idiopathic or due to organic alterations and hypothalamic hamartoma, a non-neoplasic congenital malformation, is the most frequent known organic cause. Patients with CPP due to hypothalamic hamartoma may have neurological and cognitive disfunctions. Our aims were: to evaluated the codifying region of TTF-1 and EAP1 and the promoter region of TTF-1 in patients with central pubertal disorders; to establish the prevalence, penetrance rate and inheritance mode of familial CPP and to characterize neurologic and neurocognitive aspects of patients with CPP due to hypothalamic hamartoma. We selected 133 patients with central pubertal disorders idiopathic CPP (n=71), CPP due to hypothalamic hamartoma (n=15) and normosmic isolated hypogonadropic hypogonadism (nIHH) (n=47) - and controls (n=53). TTF-1 and EAP1 genes were amplified and sequenced. Polyglutamine and polyalanine tracts of EAP1 were studied by a fragment size analyser software...

Adenocarcinoma primario de pulmón metastásico a schwannoma: un caso de metástasis de tumor a tumor / Tumor-to-tumor metastasis: pulmonary adenocarcinoma metastatic to Schwannoma

The coexistence of multiple primary malignant tumors in the same host is not unusual; however, tumor-to-tumor metastasis is rare. According to previous publications, the most common recipient tumor is renal cell carcinoma, and lung carcinoma is the most frequent donor site. According our bibliographic search we are presenting the first published case of primary pulmonary moderately differentiated adenocarcinoma metastatic to a schwannoma, demonstrated with Thyroid Transcription Factor 1 (TTF-1); immunostaining has become an important tool for guiding diagnosis of adenocarcinoma.

La coexistencia de múltiples tumores malignos primarios en un huésped no es un evento infrecuente. Sin embargo, la presencia de una neoplasia con metástasis en otra neoplasia (metástasis de tumor a tumor) es una entidad inusual, según lo publicado en la literatura el tumor receptor más frecuente es el carcinoma de células renales y el donante el carcinoma de pulmón. En el siguiente reporte se presenta un caso de adenocarcinoma moderadamente diferenciado metastásico a schwannoma, donde por inmunomarcaje con el Factor 1 de Transcripción Tiroidea (TTF-1) se demostró el origen pulmonar de la lesión, este correspondería al primer caso según nuestra revisión bibliográfica.

Effect of High Concentration of Estradiol on Thyroid Specific Genes Expression and Cell Growth / 대한내분비학회지

BACKGROUND: Since various thyroid diseases have dominant prevalence in women, it has been suggested that female sex hormone have important role on thyroid cell physiology. Interestingly, many thyroid disorders are newly diagnosed or changed their course around the period of high estrogen status, such as pregnancy. In this study, we questioned whether high concentration of estrogen could modulate thyroid cell function. METHODS: We treated normal rat thyroid FRTL-5 cell line with different time and concentration of estradiol. Using cell count, FACscan, and Northern blot analysis, we compared the changes of cell growth, cell cycle progression and thyroid specific genes expression. To evaluate the influence of thyroid stimulating hormone (TSH), all experiment was designed as two different sets, with (6H) or without TSH (5H). RESULTS: The concentration of 10-1000 nM estradiol had definite stimulatory function on thyroid cell growth in 5H condition as concentration dependent manner. FACscan revealed the increased cell growths were related to G1/S progression. The Pax-8, TTF-1 and NIS gene expressions were dramatically increased in 10-1000 nM of estradiol, too. With TSH (6H), however, we could not find any cell growth stimulating effects with 10-1000 nM of estradiol. CONCLUSION: High concentration of estradiol is one of important control factor for thyroid growth and thyroid specific genes expression, especially in 5H condition. It indicate that exposure to high concentration of female sex hormone, such as pregnancy, can be a direct stimulating factor to various thyroid function and related to autoimmune or nodular thyroid diseases around the period of pregnancy.

Primary Signet Ring Cell Carcinoma of the Lung: A Case Report / 결핵및호흡기질환

Signet ring cell carcinoma (SRCC) of the lung is a rare variant of pulmonary adenocarcinoma. Because the majority of SRCCs seen in the lung are metastatic tumors from stomach, colon, or breast, the differentiation of primary SRCC from metastatic SRCC is important but may be problematic. Recently, immunohistochemical studies are known to be valuable in determining primary sites of SRCC. Herein, we presented a case of primary signet ring cell carcinoma of the lung in a 67-year-old man. Even though radiographic findings of our case were more suggestive of metastatic orgin of SRCC in the lung, we could finally conclude that lung was the primary site of SRCC in this case with the help of immunohistochemical studies (TTF-1 and CK7 positive and CK 20 negative) and other diagnostic work up.

Effects of USF-1, USF-2, PTEN and Thyroid Transcription Factors on the Function and Growth in FRTL-5 Cells / 대한내분비학회지

BACKGROUND: Upstream stimulatory factors (USFs) and PTEN are known to be tumor suppressants. USFs and PAX-8 were reported to be the functional competitors in sodium iodide symporter (NIS) gene expression. We investigated the effects of USF-1, USF-2, PTEN, and thyroid-specific transcription factors (TTF-1, PAX-8) on the function and growth of thyrocytes of FRTL 5 rat thyroid cells. METHODS: Complementary DNAs of the USF-1, USF-2, PTEN, TTF-1 (homeodomain), and PAX-8 were synthesized from RNA extracted from FRTL-5using an RT-PCR kit. Each of them was transiently transfected to the FRTL-5 cells using the lipofectamine after being cloned into the pcDNA3.1 vectors. Stable cell lines, which were transfected by USF-1, PTEN, TTF-1, and PAX-8, were also obtained from the FRTL-5 cells, respectively. Extracellular cAMP concentrations were measured after 24 hours of incubation with varying concentrations of bTSH (0.1~100 mIU/mL). After, [Methyl-3H] thymidine uptake or 5-bromo-2'-deoxyuridine (BrdU) assay was performed. RESULTS: USF-1 and USF-2 significantly increased cAMP levels and decreased thymidine uptake in both transiently and stably transfected cells (p<0.01). PTEN had a tendency to increase both the cAMP levels and BrdU uptake in stable cells, but had a tendency to decrease thymidine uptake in transiently transfected cells. TTF-1 significantly increased the cAMP levels and either thymidine or BrdU uptake in both transiently and stably transfected cells (p<0.05). PAX-8 significantly increased both the cAMP levels and BrdU assay in stable cells, but in transiently transfected cells, it significantly decreased cAMP concentrations (p<0.01). CONCLUSIONS: These results suggested that both the USF-1 and USF-2 play a role in suppressing the growth of thyrocytes but at the same time, they kept the ability to produce cAMP after TSH stimulation. They had opposing effects on TTF-1 and PAX-8 in terms of the proliferation of thyrocytes

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 INTERRELATED POLYPEPTIDES AND THEIR REGULATORY FUNCTION IN MOUSE FETAL LUNGS / 解剖学报

Objective To observe the distributions of epidermal growth factor receptor(EGFR),transforming growth factor ?(TGF ? 1,? 2,? 3)and thyroid transcription factor 1(TTF 1)in developing lungs,and to discuss their functions and relationships each other. Methods The expression of EGFR and TGF ? was examined in mouse fetal lungs by immunohistochemistry.TIGER image analysiser was used in TTF 1 quantitative study. Results 1.In the early developmental phase,EGFR localized in the epithelium of airway surface,TTF 1 was expressed predominantly in the nuclei of distal lung buds and TGF ? was expressed in the bronchioles with localization patterns.2.At the late developmental phase,the positive reactions of EGFR and TTF 1 were mainly detected in alveolar cells.TGF ? expressed in mesenchymal at high levels.3 The average optical density(A A )of TTF 1 in the distal epithelial cells increased gradually during the development,while their volume(VOL)and volume integrated optical density(VI A )all decreased.Conclusion\ The functions of EGFR,TGF ? and TTF 1 might be respectively different at different developmental stages.They not only stimulate the process of branching morphogenesis,but also modulate epithelial maturation and differentiation.\;[