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Spontaneous rupture of a metastatic liver tumour is rarely documented in the literature when compared to hepatocellular carcinoma and other liver lesions, especially from a lung primary. We report a case of ruptured liver metastasis from an adenocarcinoma of the lung mimicking ruptured liver abscess, challenging the clinical diagnosis. A 42-year-female patient presented to a tertiary care institute in 2020 with complaints of abdominal pain, breathlessness and fever. On examination, the patient was tachypnoeic with a right hypochondriac mass. A contrast-enhanced computed tomography of abdomen and thorax revealed an ill-defined heterogeneously enhancing lesion in the liver with a communicating subcapsular collection and hypo-enhancing lesions in the left lobe and heterogeneously enhancing lesion in the left lung. Adenocarcinoma of the lung with hepatic metastasis was confirmed with a core needle biopsy. The patient was managed conservatively with intravenous antibiotics, intercostal drainage tube and gefitinib. However, despite best efforts, the patient succumbed to the disease. [ABSTRACT FROM AUTHOR]

Thyroid hemiagenesis (THA) is an inborn absence of one thyroid lobe of largely unknown etiopathogenesis. The aim of the study was to reveal genetic factors responsible for thyroid maldevelopment in two siblings with THA. None of the family members presented with congenital heart defect. The samples were subjected to whole-exome sequencing (WES) (Illumina, TruSeq Exome Enrichment Kit, San Diego, CA 92121, USA). An ultra-rare variant c.839C>T (p.Pro280Leu) in NKX2-5 gene (NM_004387.4) was identified in both affected children and an unaffected father. In the mother, the variant was not present. This variant is reported in population databases with 0.0000655 MAF (GnomAD v3, dbSNP rs761596254). The affected amino acid position is moderately conserved (positive scores in PhyloP: 1.364 and phastCons: 0.398). Functional prediction algorithms showed deleterious impact (dbNSFP v4.1, FATHMM, SIFT) or benign (CADD, PolyPhen-2, Mutation Assessor). According to ACMG criteria, variant is classified as having uncertain clinical significance. For the first time, NKX2-5 gene variants were found in two siblings with THA, providing evidence for its potential contribution to the pathogenesis of this type of thyroid dysgenesis. The presence of the variant in an unaffected parent, carrier of p.Pro280Leu variant, suggests potential contribution of yet unidentified additional factors determining the final penetrance and expression. [ABSTRACT FROM AUTHOR]

Introduction: Diagnosing Non-Small Cell Lung Carcinoma (NSCLC) by morphology on small biopsy specimens are on demand. With major advances in molecular testing of lung cancers and introduction of targeted therapies, accurate subtyping of NSCLC has become essential. Immunophenotyping with various immunomarkers is helpful in identification of different tumour subtypes. As sparing material for molecular testing is mandatory, a minimalistic Immunohistochemistry (IHC) based diagnostic approach is warranted by means of reliable and accessible immunomarkers. In this study, one immunomarker Thyroid Transcription Factor (TTF1) for glandular and protein40 (p40) for squamous differentiation was applied to maximise the proportion of accurately subtyped NSCLC on small biopsy specimens. Aim: To find utility of TTF1/p40 minimalistic immunopanel in subtyping NSCLC especially those with ambiguous morphology. Materials and Methods: This retrospective observational study was conducted from 15 December 2020 to 5 March 2021 in a tertiary care hospital in which ninety-three (mean age 64.8 years, Male:female ratio 4.8:1) consecutive lung biopsies from suspected lung carcinoma obtained from January 2019 to December 2020 were studied. The morphological diagnosis and diagnosis after application of TTF1 and P40 minimalistic immunopanel was evaluated using chi-square test. The p-value

Thyroid hemiagenesis (THA) is an inborn absence of one thyroid lobe of largely unknown etiopathogenesis. The aim of the study was to reveal genetic factors responsible for thyroid maldevelopment in two siblings with THA. None of the family members presented with congenital heart defect. The samples were subjected to whole-exome sequencing (WES) (Illumina, TruSeq Exome Enrichment Kit, San Diego, CA 92121, USA). An ultra-rare variant c.839C>T (p.Pro280Leu) in NKX2-5 gene (NM_004387.4) was identified in both affected children and an unaffected father. In the mother, the variant was not present. This variant is reported in population databases with 0.0000655 MAF (GnomAD v3, dbSNP rs761596254). The affected amino acid position is moderately conserved (positive scores in PhyloP: 1.364 and phastCons: 0.398). Functional prediction algorithms showed deleterious impact (dbNSFP v4.1, FATHMM, SIFT) or benign (CADD, PolyPhen-2, Mutation Assessor). According to ACMG criteria, variant is classified as having uncertain clinical significance. For the first time, NKX2-5 gene variants were found in two siblings with THA, providing evidence for its potential contribution to the pathogenesis of this type of thyroid dysgenesis. The presence of the variant in an unaffected parent, carrier of p.Pro280Leu variant, suggests potential contribution of yet unidentified additional factors determining the final penetrance and expression.

Thyroid transcription factor 1 (TTF-1) is considered a highly sensitive and specific marker for primary lung adenocarcinoma. However, in recent years retrospective studies of tumor samples have confirmed that, although rare, TTF-1 can also be expressed in colorectal adenocarcinoma. There are a few case reports of patients with TTF-1-positive colon adenocarcinoma in the medical literature but none of TTF-1-positive rectal adenocarcinoma. Here, we present a case of rectal adenocarcinoma with lung metastasis found to be TTF-1 positive on immunohistochemistry. A review and discussion of the available literature is also included.

Lung cancer is the most common malignancy throughout the world. Non-small cell lung carcinoma is the most common type and squamous cell type is the most common in India. Patients mostly present with chest related symptoms and signs. Isolated skeletal muscle metastasis (ISMM) is rarely seen. We describe a patient who presented with ISMM and hypercalcemia without any pulmonary symptoms.

Published reports of neoplasms in Thomson's gazelles ( Eudorcas thomsonii) are very rare, but thyroid tumors were the most common neoplasm of this species, accounting for 12% of reported pathologies in a 1998-2012 retrospective study of cases submitted for histologic review of grossly enlarged thyroid glands. This report describes the histological and immunohistochemical characteristics of thyroid neoplasms in 10 Thomson's gazelles from five different zoological collections. Neoplasms were submitted as biopsies from six gazelles or collected during necropsy from four gazelles. The most common clinical findings included a palpable mass on the ventral neck and progressive weight loss. Radiographic mineral density was detected in one of the neoplastic masses. Histologically, the neoplasms were classified as microfollicular thyroid adenoma ( n = 2), solid thyroid adenoma ( n = 2), papillary thyroid adenoma ( n = 1), and solid thyroid carcinoma ( n = 5). Neoplastic cells in all 10 neoplasms were positive for thyroid transcription factor 1 and thyroglobulin, but negative for calcitonin. While five cases had histologic features of malignancy, there was no evidence of metastatic disease either clinically (biopsies) or on necropsy. Numerous concurrent diseases, including cardiomyopathies and nephropathies, were present and led to choice for euthanasia in several cases. [ABSTRACT FROM AUTHOR]

Objective To elucidate the molecular mechanism which causes thyroid dysgenesis (TD) in a boy with brain-lung-thyroid syndrome. Design, patients, measurements We describe a patient with TD, respiratory disease and cerebral palsy who is heterozygous for mutations in two different genes, the PAX8 (p.E234K) and the NKX2.1 (p.A329GfsX108). In vitro studies were performed to functionally characterize these mutations. Congenital hypothyroidism (CH) was identified by neonatal screening associated with a hypoplastic thyroid gland. Postpartum he developed a brain-lung-thyroid syndrome with severe respiratory failure, symptomatic epilepsy and a considerable psychomotor retardation. The DNA-binding capability and the transcriptional activity of the two mutated transcription factors were investigated in vitro. Results The NKX2.1 mutation did not show any transcriptional activity and had almost no DNA-binding. The PAX8 mutation was normally located to the nucleus and showed a normal transactivation and a normal binding to the known downstream targets. Conclusions The molecular defect explaining the phenotype of brain-lung-thyroid syndrome was identified. To what extent the PAX8 mutation contributes to the phenotype needs to be further investigated. We recommend to screen patients with CH and TD for mutations in all known TD candidate genes. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma is a malignant neoplasm mostly originating from the salivary glands but it has also been reported to arise in several other sites including the skin. Primary cutaneous adenoid cystic carcinoma (PCACC) was first described by Raul Boggio in 1975. Case reports then followed describing similar tumors with some reporting a metastatic tumor at presentation, and others reporting late metastases occurring as late as 21 years after initial diagnosis. We report a case of a 65 year old male patient who presented with pulmonary metastases from a scalp adenoid cystic carcinoma diagnosed 5 years previously. A brief literature review is included which focuses on discussion of the behavior and prognosis of these lesions and their potential to metastasize. Metastasis of this tumor is more ominous than originally suggested; as the metastatic rate is close to 10% and can appear after a long time span which mandates a long term follow up. We also challenge the reliance on thyroid transcription factor (TTF1) immuno-histochemical stain to differentiate primary pulmonary from metastatic adenoid cystic carcinoma. Our case and the experience of other researchers reveal that TTF1 can be positive in pulmonary metastases but negative in the primary lesion. [ABSTRACT FROM AUTHOR]

The replacement of regenerated thyroid follicular cells (TFCs) is a promising therapeutic strategy for patients with hypothyroidism. Here, we have succeeded in inducing functional TFCs from human-induced pluripotent stem cells (iPSCs) in scalable suspension culture. Differentiation of iPSCs with Activin A treatment produced Sox17- and FoxA2-expressing definitive endodermal cells that also expressed thyroid transcription factors Pax8 and Nkx2-1. Further treatment with thyroid-stimulating hormone (TSH) induced TFCs expressing various types of thyroid proteins including TSH receptor, sodium–iodide symporter, thyroglobulin, and thyroid peroxidase. Interestingly, differentiated cells secreted free thyroxine in vitro. These results indicate successful differentiation of human iPSCs to functional TFCs that may enable us to fabricate thyroid tissues for regenerative medicine and disease models.

Aims: Lung cancer is the most common malignancy throughout the world. Nonsmall cell lung cancer (NSCLC) is the most common type, and squamous cell type is most common in India. Mostly, patients present with chest-related symptoms and signs. Isolated skeletal muscle metastasis (ISMM) is rarely seen. The aim was to see muscle metastasis and its prognosis. Materials and Methods: We are presenting our data of 8 years about this common malignancy with relation to muscle metastasis, either alone or with other system metastasis. Results: Muscle metastasis is seen 1.5% of patients, with male: female of 8:1. Overall median survival was 15 months and progression-free survival was 12 months. Conclusion: One peculiarity seen was ISMM with no pulmonary system and severe paraneoplastic hypercalcemia. Local therapy may be having an impact on overall survival in metachronous muscle involvement. [ABSTRACT FROM AUTHOR]

Metastatic extra-adrenal paragangliomas are very rare and can represent diagnostic challenges. We report a case of 69-year-old man with a tumor of the right shoulder. Histologic and immunohistochemical examinations confirmed the diagnosis of paraganglioma. Surprisingly, tumor cells were diffusely thyroid transcription factor 1 (TTF-1) positive. Succinate dehydrogenase complex subunit B (SDHB) deficiency has not been detected. Inherited syndromes associated with paragangliomas were ruled out. The primary tumor was identified in the mediastinum. This is the first report of TTF-1 expression in paraganglioma. To avoid misdiagnosis, careful clinical and pathological examination of any tumor with organoid growths pattern is necessary. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) of the skin is a rare, aggressive, malignant neuroendocrine neoplasm. The tumor classically demonstrates positive immunohistochemistry (IHC) staining for chromogranin A(ChrA), cytokeratin 20 (CK20), neuron specific enolase (NSE) and/or achaete-acute complex-like 1 (MASH1). The newly identified Merkel cell polyomavirus (MCPyV) has been found to be associated with most MCC cases. The primary histologic differential diagnoses of cutaneous MCC is small cell primary bronchogenic carcinoma (SCLC); moreover, both are of neuroendocrine origin. SCLC accounts for approximately 10-15% of all primary lung cancer cases; this histologic subtype is a distinct entity with biological and oncological features distinct from non-small cell lung cancer (NSCLC). In contradistinction to MCC, SCLC is classically IHC positive for cytokeratin 7 (CK7) and transcription factor (TTF-1). Similar to SCLC, MCC cell lines may be classified into two different biochemical subgroups designated as Classic and Variant. In our review and case report, we aim to emphasize the importance of a multidisciplinary approach to the approach to this difficult differential diagnosis. We also aim to comment about features of the cells of origin of MCC and SCLC; to summarize the microscopic features of both tumors; and to review their respective epidemiologic, clinical, prognostic and treatment features. We want to emphasize the initial workup study of the differential diagnosis patient, including evaluating clinical lymph nodes, a clinical history of any respiratory abnormality, and chest radiogram. If a diagnosis of primary cutaneous MCC is confirmed, classic treatment includes excision of the primary tumor with wide margins, excision of a sentinel lymph node, and computed tomography, positron emission tomography and/or Fluorine-18-fluorodeoxyglucose positron emission tomography scan studies

Thyroid transcription factor 1 (TTF-1) is considered a highly sensitive and specific marker for primary lung adenocarcinoma. However, in recent years retrospective studies of tumor samples have confirmed that, although rare, TTF-1 can also be expressed in colorectal adenocarcinoma. There are a few case reports of patients with TTF-1-positive colon adenocarcinoma in the medical literature but none of TTF- 1-positive rectal adenocarcinoma. Here, we present a case of rectal adenocarcinoma with lung metastasis found to be TTF-1 positive on immunohistochemistry. A review and discussion of the available literature is also included. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to analyze the frequency of Thyroid Transcription Factor (TTF)-1 expression in small cell lung cancer (SCLC) and its value for the diagnosis of SCLC, the response to first line treatment as well as the prognostic impact on overall survival (OS). Methods: We analyzed a total of 294 patients (m, n = 184; f, n = 110) with SCLC (stage IIIA, n = 32; IIIB, n = 87; IV, n = 175) diagnosed in our institution between January 2005 and December 2008. Patient's characteristics comprising age, gender, histology and first line treatment were included into the analyses. For the follow-up of patients the governmental death registrar was used. The TTF-1 immunostaining was prospectively performed. CT scans of all patients were reviewed and response to treatment was evaluated using the Response Evaluation Criteria In Solid Tumors 1.0 (RECIST) criteria. Results: A total of 221 of the 294 patients were eligible for analysis. Patients with TTF-1-positive SCLC had a median OS of 374 (95% CI 306-442) days. The OS of patients with TTF1-negative SCLC was 290 (95% CI 191-389) days, which was not significantly shorter (p = 0.254). Also stratification for tumor stage did not reveal significant difference in OS. Analyzing the disease control rate (DCR) in patients with metastatic disease (stage IV), we observed a significantly (p = 0.006) improved response to treatment in the group of patients with TTF-1-expression (DCR 86% vs. 56%). Regarding the overall response rates (ORR) in the entire population, there was no difference observed between both subgroups. (TTF-1-pos. 75.3% vs. TTF-1-neg. 71.4%; p = 0.642). Conclusions: The diagnostic information of TTF-1 in SCLC seems to be limited. TTF-1 had no prognostic value concerning OS, but may serve as a predictor for response to first line chemotherapy. [ABSTRACT FROM AUTHOR]

Nkx2 homeodomain transcription factors are involved in various developmental processes and cell specification: e.g . in mammals, NKX2-1 is essential for thyroid-specific gene expression and thyroid morphogenesis. Among Nkx2 proteins, information is still very limited for Nkx2-4. In the present study, we have identified three distinct cDNAs encoding Nkx2-4 isoforms (Nkx2-4a, -b, and -c) from the rainbow trout thyroid tissue, and characterized their transcriptional properties. The trout Nkx2-4 proteins were all predicted to conserve three characteristic domains: the tinman-like amino terminal decapeptide, the NK2 homeodomain, and the NK2-specific domain, and also share 75–89% amino acid similarity. It was shown by dual luciferase assay that Nkx2-4a and Nkx2-4b, but not Nkx2-4c, significantly activated transcription from a cotransfected rat thyroglobulin (TG) promoter. An electrophoretic mobility shift assay indicated that all the Nkx2-4 isoforms could bind to the TG promoter, implying that the faint transcriptional activity of Nkx2-4c might result from some critical amino acid substitution(s) outside the homeodomain. RT-PCR analysis revealed similar tissue distribution patterns for Nkx2-4a and Nkx2-4b mRNAs. Both mRNAs were expressed abundantly in the thyroid, and weakly in the testis. On the other hand, Nkx2-4c mRNA was detected in the ovary as well as in the thyroid. The expression sites of Nkx2-4c mRNA were localized, by in situ hybridization histochemistry, to the ovarian granulosa cells and to the thyroid follicular cells. The results suggest that in the rainbow trout, Nkx2-4a and Nkx2-4b might play a major role in TG gene transcription whereas Nkx2-4c might have some functions in the ovary as well as the thyroid. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aim was to determine if combined pemetrexed, cisplatin, and cetuximab was efficacious and safe as first-line treatment in advanced nonsquamous non-small cell lung cancer (NSCLC). Patients and methods: In this single-arm, multicenter clinical trial, patients with Stage IIIB/IV nonsquamous NSCLC received first-line therapy consisting of pemetrexed (500mg/m2) and cisplatin (75mg/m2) on Day 1 (21-day cycles) plus weekly cetuximab (400mg/m2 loading dose, then 250mg/m2) for 4–6 cycles. Non-progressing patients received maintenance therapy consisting of pemetrexed and cetuximab as above until disease progression. All patients received vitamin supplementation, dexamethasone, and antihistamine prophylaxis. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), 1-year survival rate, translational research (TR) and safety. Results: Of the 113 patients receiving study drug, 109 were protocol-qualified. All patients completed ≥1 cycle of induction, and 51 (45%) and 49 (43%) patients completed ≥1 cycle of maintenance with pemetrexed and cetuximab, respectively. The ORR (n =109) was 38.5% (80% confidence interval [CI], 32.3–45.1%), all partial responses. Median PFS was 5.8 (80% CI, 4.4–6.7) months. One-year survival rate was 45% (80% CI, 39–51%). In exploratory analyses, there was some preliminary evidence of potential prognostic relationships with efficacy outcomes for epidermal growth factor receptor and thyroid transcription factor-1 protein expression, but not for KRAS mutation or for thymidylate synthase or folate receptor-alpha protein expression. Seventy-three (64.6%) patients had study drug-related Grade 3/4 adverse events (AEs). Drug-related serious AEs were reported in 31 (27.4%) patients. There were 3 (2.7%) potentially drug-related deaths on-study or within 30 days of follow up. Conclusion: Pemetrexed, cisplatin, and cetuximab appeared efficacious and tolerable in advanced nonsquamous NSCLC patients. The TR outcomes are hypothesis-generating given the study's size and nonrandomized nature. [Copyright &y& Elsevier]

Introduction: Merkel cell carcinoma (MCC) of the skin is a rare, aggressive, malignant neuroendocrine neoplasm. The tumor classically demonstrates positive immunohistochemistry (IHC) staining for chromogranin A(ChrA), cytokeratin 20 (CK20), neuron specific enolase (NSE) and/or achaete-acute complex-like 1 (MASH1). The newly identified Merkel cell polyomavirus (MCPyV) has been found to be associated with most MCC cases. The primary histologic differential diagnoses of cutaneous MCC is small cell primary bronchogenic carcinoma (SCLC); moreover, both are of neuroendocrine origin. SCLC accounts for approximately 10-15% of all primary lung cancer cases; this histologic subtype is a distinct entity with biological and oncological features distinct from non-small cell lung cancer (NSCLC). In contradistinction to MCC, SCLC is classically IHC positive for cytokeratin 7 (CK7) and transcription factor (TTF-1). Similar to SCLC, MCC cell lines may be classified into two different biochemical subgroups designated as Classic and Variant. In our review and case report, we aim to emphasize the importance of a multidisciplinary approach to the approach to this difficult differential diagnosis. We also aim to comment about features of the cells of origin of MCC and SCLC; to summarize the microscopic features of both tumors; and to review their respective epidemiologic, clinical, prognostic and treatment features. We want to emphasize the initial workup study of the differential diagnosis patient, including evaluating clinical lymph nodes, a clinical history of any respiratory abnormality, and chest radiogram. If a diagnosis of primary cutaneous MCC is confirmed, classic treatment includes excision of the primary tumor with wide margins, excision of a sentinel lymph node, and computed tomography, positron emission tomography and/or Fluorine-18- fluorodeoxyglucose positron emission tomography scan studies. [ABSTRACT FROM AUTHOR]

Abstract: Benign hereditary chorea (BHC, MIM 118700) is a rare autosomal dominant disorder manifesting with chorea in conjunction with hypothyroidism and respiratory problems, a triad also named “brain-lung-thyroid syndrome”. BHC is characterized by childhood onset with minimal or no progression into adult life and normal cognitive function. The genetic basis of BHC has been partially resolved, when mutations in the TTF1 gene on chromosome 14q13 encoding the thyroid transcription factor-1 have been identified in a number of BHC patients, suggesting that aberration of TTF1 transcriptional function or haploinsufficiency is associated with this disorder. TTF1 (also known as TITF1, TEBP or NKX2–1), belonging to the NKX2 homeodomain transcription factor family, has been implicated in several important molecular pathways essential for brain, thyroid and lung morphogenesis. Clinical evaluation of TTF1 gene mutations carrier patients exposed the involvement of each of the triad’s components characterized by heterogeneity between index cases and even within families. This review highlights the current updates on expanded clinical aspects of BHC, imaging and treatment experience, its genetic markers, proposed molecular mechanisms, animal models and link to cancer. [Copyright &y& Elsevier]

Human respiratory syncytial virus (hRSV) is a pneumovirus that causes significant respiratory disease in premature and full-term infants. It was our hypothesis that a common strain of RSV, strain A2, would infect, cause pulmonary pathology, and alter respiratory epithelial innate immune responses in neonatal lambs similarly to RSV infection in human neonates. Newborn lambs between 2 and 3 days of age were inoculated intrabronchially with RSV strain A2. The lambs were sacrificed at days 3, 6, and 14 days postinoculation. Pulmonary lesions in the 6 -day postinoculation group were typical of RSV infection including bronchiolitis with neutrophils and mild peribronchiolar interstitial pneumonia. RSV mRNA and antigen were detected by qPCR and immunohistochemistry, respectively with peak mRNA levels and antigen at day 6. Expression of surfactant proteins A and D, sheep beta-defensin-1 and thyroid transcription factor-1 mRNA were also assessed by real-time qPCR. There was a significant increase in surfactant A and D mRNA expression in RSV -infected animals at day 6 postinoculation. There were no significant changes in sheep beta -defensin-1 and thyroid transcription factor-1 mRNA expression. This study shows that neonatal lambs can be infected with RSV strain A2 and the pulmonary pathology mimics that of RSV infection in human infants thereby making the neonatal lamb a useful animal model to study disease pathogenesis and therapeutics. RSV infection induces increased expression of surfactant proteins A and D in lambs, which may also be an important feature of infection in newborn infants. [ABSTRACT FROM AUTHOR]

Abstract: Thyroglobulin (Tg) is a large molecule containing 2750 amino acids with a molecular weight of 330 kD and twenty putative N-linked glycosylation sites. Tg gene expression is regulated by thyroid transcription factor 1 (TTF-1) and human paired box 8 (Pax-8). Iodinated Tg is stored in the lumen of the thyroid follicles and is released in response to specific hormonal stimulation by thyroid stimulating hormone (TSH). Following Tg reabsorption by thyrocytes and subsequent degradation, thyroid hormones triiodothryronine (T3) and thyroxine (T4) are secreted in the bloodstream. Mutations within the Tg gene cause defective thyroid hormone synthesis, resulting in congenital hypothyroidism. Thyroid carcinoma may develop from dyshormonogenic goiters due to Tg mutation. Post-thyroidectomy Tg levels are apparently associated with prognosis of papillary and follicular thyroid carcinomas and may predict tumor recurrence and metastastic potential. The detection of Tg by biochemical and molecular means has important diagnostic significance due to its pleiotropic roles in identification of tissue of thyroid origin, differentiation, and post-operative follow-up. [Copyright &y& Elsevier]

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. We hypothesized that TTF-1 is expressed in human lung cancer cell lines and its expression might be related to the expression of surfactant protein. To test this, expressions of TTF-1 and surfactant protein A (SP-A) were immunohistochemically evaluated in 16 human lung cancer cell lines. In addition, expressions of mRNAs for TTF-1 and SP-A were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing. As a result, nuclear staining of TTF-1 was observed in two of six adenocarcinoma cell lines, none of seven small cell lung cancer cell lines, and none of three squamous lung cancer cell lines. Among the 16 cell lines, six cell lines (PC3, LC2/Ad, A549, RERF-LC-OK, HI1017, and PC9) expressed significant amounts of mRNA for TTF-1. 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. One of the two adenocarcinoma cell lines those showed positive nuclear staining and cytoplasmic SP-A staining released a significant amount of SP-A in culture supernatant. Our present study demonstrates that the frequency of TTF-1 expression in the nucleus was very low in human lung cancer cell lines; however, their cytoplasmic positivities should be further investigated. [Copyright &y& Elsevier]

The replacement of regenerated thyroid follicular cells (TFCs) is a promising therapeutic strategy for patients with hypothyroidism. Here, we have succeeded in inducing functional TFCs from human-induced pluripotent stem cells (iPSCs) in scalable suspension culture. Differentiation of iPSCs with Activin A treatment produced Sox17- and FoxA2-expressing definitive endodermal cells that also expressed thyroid transcription factors Pax8 and Nkx2-1. Further treatment with thyroid-stimulating hormone (TSH) induced TFCs expressing various types of thyroid proteins including TSH receptor, sodium-iodide symporter, thyroglobulin, and thyroid peroxidase. Interestingly, differentiated cells secreted free thyroxine in vitro . These results indicate successful differentiation of human iPSCs to functional TFCs that may enable us to fabricate thyroid tissues for regenerative medicine and disease models.