Thyroid transcription factor-1 is highly sensitive and specific in differentiating metastatic pulmonary from extrapulmonary adenocarcinoma in effusion fluid cytology specimens

Ng, Wai-Kuen; Chow, Janson C. Y.; Ng, Peter K. H.

doi:10.1002/cncr.10310

Cited by 58 publications

(51 citation statements)

References 31 publications

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“…1,2 As the lung is one of the most common sites of metastasis, TTF-1 is considered as a reliable marker to distinguish between primary lung carcinoma and lung metastasis, especially when dealing with an adenocarcinoma or a large-cell carcinoma. [3][4][5][6] It is also considered as a reliable marker in the differential diagnosis between pleural localization of lung origin carcinoma and malignant mesothelioma. 7 Two main commercial available clones of monoclonal antibodies have been raised against TTF-1 for immunohistochemical use, 8G7G1/1 and SPT24, their diagnostic value in determining the lung or thyroid origin of adenocarcinoma has not yet been compared.…”

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confidence: 99%

Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin

et al. 2005

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Thyroid transcription factor-1 (TTF-1) is considered as a reliable marker for differential diagnosis in distinguishing primary adenocarcinomas of the lung from extrathoracic origins. We previously reported the first case of lung metastasis of colorectal origin, with nuclear expression of TTF-1. As most previous studies were performed on series of extrathoracic primary tumors, we raised the question of a possible role of lung microenviroment in TTF-1 expression. We investigated the rate of TTF-1 expression in lung metastases of extrathoracic adenocarcinomas and compared results of immunohistochemistry performed with different primary antibodies. Two different clones of antibodies (8G7G1/1 from Dako, SPT24 from Novocastra) raised against TTF-1 were used on 56 lung-metastatic malignant tumors, 41 from colorectal origin. A series of primary colorectal (90 cases) and primary pulmonary adenocarcinomas (86 cases) were also investigated. Four of 41 (10%) lung metastases of colorectal adenocarcinomas displayed a nuclear staining for TTF-1 with SPT24 clone. Three of the four positive cases displayed similar nuclear staining in primary and/or other extrathoracic metastatic sites as well as four of 90 (5%) primary colorectal adenocarcinomas, ruling out the role of lung microenvironment. None of them was positive with 8G7G1/1 clone. Sensitivity between two sets of antibodies was compared in 86 primary pulmonary adenocarcinomas. Nuclear staining was detected in 72 cases (84%) with Novocastra's antibody and 56 cases (65%) with Dako's. Significant discordance was observed (Po 0.01). These results suggest that the diagnostic virtue of TTF-1 detection depends on the used antibody's clone. The SPT24 clone seems to have a stronger affinity for TTF-1 protein but may lead to a few positive colorectal adenocarcinomas. Keywords: TTF-1; lung; carcinoma; metastasis; colorectal Thyroid transcription factor-1 (TTF-1) is a tissuespecific transcription factor expressed in the epithelial cells of thyroid and lung (type II pneumocytes and Clara cells). Carcinomas arising from lung and thyroid also show frequent TTF-1 expression. 1,2 As the lung is one of the most common sites of metastasis, TTF-1 is considered as a reliable marker to distinguish between primary lung carcinoma and lung metastasis, especially when dealing with an adenocarcinoma or a large-cell carcinoma. [3][4][5][6] It is also considered as a reliable marker in the differential diagnosis between pleural localization of lung origin carcinoma and malignant mesothelioma. 7 Two main commercial available clones of monoclonal antibodies have been raised against TTF-1 for immunohistochemical use, 8G7G1/1 and SPT24, their diagnostic value in determining the lung or thyroid origin of adenocarcinoma has not yet been compared. Most of the studies show the high specificity of TTF-1 detection and have been published used the 8G7G1/1 clone. We previously reported one case of lung metastasis of colorectal origin, which showed a focal nuclear staining with the anti-TTF-1 antibody (clone SPT24)...

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Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin

et al. 2005

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“…In such cases, positivity for thyroid transcription factor 1 (TTF1; a protein normally expressed in thyroid and lung parenchyma) is thought to indicate the primary lung origin of the tumour. [4][5][6] Our report deals with the technical feasibility and preliminary results of assessment of TTF-1 on peroperative frozen sections.…”

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Peroperative frozen section analysis of TTF-1 antigen expression

Camilleri-Broët

Alifano²,

Morcos³

et al. 2004

Journal of Clinical Pathology

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“…2,3,6,8,[10][11][12][19][20][21]26,27,37,38,42,43 Metastatic pulmonary carcinomas also express TTF-1. 14,17,25,[33][34][35] We recently reported the detection of TTF-1 in most canine thyroid follicular neoplasms and in approximately half of canine C-cell tumors. 32 During that study, we observed TTF-1 reactivity in some pulmonary neoplasms.…”

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Usefulness of Thyroid Transcription Factor-1 Immunohistochemical Staining in the Differential Diagnosis of Primary Pulmonary Tumors of Dogs

2005

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Abstract. In a previous study, we characterized the reactivity of monoclonal antibody (MoAb) 8G7G3/1 to thyroid transcription factor-1 (TTF-1) in canine thyroid tumors. In this study, we have examined the reactivity of this antibody in 120 canine pulmonary tumors, including 78 primary epithelial tumors. Tissues had been fixed in formalin and routinely processed for histopathology. Nuclear staining for TTF-1 was detected in 64.2% of primary pulmonary epithelial tumors. The most common TTF-1-reactive tumor types were bronchioloalveolar carcinomas and bronchogenic carcinomas. Staining was diffuse, heterogeneous, or patchy. Nonpulmonary, metastatic epithelial tumors, except two of two thyroid carcinomas, did not react with antibody 8G7G3/1. Mesotheliomas and other mesenchymal tumors were also negative for this marker. A reduction or loss of reactivity was apparent in pulmonary epithelial tumors archived in paraffin blocks for 7-8 years. There was slight reduction in the number of positive cells or the intensity of the reaction in control tissues fixed longer than 1 week. On the basis of our limited studies and the human literature, it appears that MoAb 8G7G3/1 to TTF-1 is a highly specific (with the exception of thyroid tumors) and moderately sensitive marker for canine pulmonary epithelial tumors.Key words: Dogs; immunohistochemistry; lungs; neoplasia; thyroid transcription factor-1.Pulmonary neoplasms are uncommon in dogs, with a prevalence of 0.1-0.9% in the overall canine population; however, when only aging dogs are considered, the percentage of animals with pulmonary tumors may reach 25%. 41 The lung is a common place for metastases of nonpulmonary neoplasms. Metastatic tumors can resemble primary pulmonary tumors microscopically, 9 making it challenging to determine the origin of the tumor on the basis of routine histopathology. Thyroid transcription factor-1 (TTF-1) is a 38-kDa homeodomain containing nuclear protein that is a member of the Nkx2 gene family. It plays a role in transcriptional activation during embryogenesis in the thyroid, diencephalon, and respiratory epithelium. 5,13,22 Thyroglobulin-producing cells, C cells, and parathyroid cells from different species express TTF-1. 15,18,39 In the lung, TTF-1 activates surfactant proteins and Clara cell secretory protein gene promoters. 5 TTF-1 is necessary for lung epithelial morphogenesis. 23 In the human fetal lung, TTF-1 is detected in nonciliated cells in airways and in type-I and type-II pneumocytes; 36 in neonates and adults, TTF-1 is primarily expressed in type-II alveolar cells and nonciliated bronchiolar epithelial cells. 16,21,36 Thyroid and pulmonary tumors of humans express TTF-1. 2,3,6,8,[10][11][12][19][20][21]26,27,37,38,42,43 Metastatic pulmonary carcinomas also express TTF-1. 14,17,25,[33][34][35] We recently reported the detection of TTF-1 in most canine thyroid follicular neoplasms and in approximately half of canine C-cell tumors. 32 During that study, we observed TTF-1 reactivity in some pulmonary neoplasms. In this study, we examin...

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Thyroid transcription factor-1 is highly sensitive and specific in differentiating metastatic pulmonary from extrapulmonary adenocarcinoma in effusion fluid cytology specimens

Cited by 58 publications

References 31 publications

Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin

Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin

Peroperative frozen section analysis of TTF-1 antigen expression

Usefulness of Thyroid Transcription Factor-1 Immunohistochemical Staining in the Differential Diagnosis of Primary Pulmonary Tumors of Dogs

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