The Value of Thyroid Transcription Factor-1 in Cytologic Preparations as a Marker for Metastatic Adenocarcinoma of Lung Origin

Hecht, Jonathan L.; Pinkus, Jack L.; Weinstein, Lisa J.; Pinkus, Geraldine S.

doi:10.1309/nl4y-fhg8-2xbc-f9xh

Cited by 99 publications

(68 citation statements)

References 11 publications

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“…Previously, to conduct studies related to biomarker positivity, researchers would first establish a hypothesis and verify it through clinical experiments, or conduct a long process of directly searching for, extracting, and collecting data through the hospital EMR and parsing the data before analysis [22][23][24][25]. Researchers often experience difficulties in securing such large volumes of data.…”

Section: Discussionmentioning

confidence: 99%

Development of biomarker positivity analysis system for cancer diagnosis based on clinical data

Yun

Hwang

Anh

et al. 2015

BME

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Abstract. In Korea, there were 224,000 new cases of cancer and 75,334 deaths caused by cancer in 2013, which was three times more than the number of death caused by heart disease, the second leading cause of death. This study proposes a biomarker positivity analysis system based on clinical data, for personalized diagnosis and therapy of cancer. Data of 78,912 cases were obtained from immunopathology and surgical pathology reports. Data on sex, age, organ, diagnosis, and biomarkers were entered into a database. To verify the reliability of the clinical data, an additional 50,450 cases from positivity-related research papers were added. The proposed biomarker positivity analysis system makes it possible to extract and combine information for searching. The positivity values are in graphical and tabular format for ease of use. With a link to the internal network of the hospital, real-time pathology reports are available. Twenty-five pathology specialists are chosen as subjects to further confirm the reliability of this system; primary assessment results demonstrate a satisfaction level of 4.7 out of 5 and a concordance rate of 79% with positive data under the same conditions as reported in the literature. In the present study, analysis methods and platforms using large volumes of clinical and literature data are developed for cancer prognoses. It is expected that these tools will benefit both healthcare professionals and non-professionals involved in cancer diagnosis and treatment.

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Section: Discussionmentioning

confidence: 99%

Development of biomarker positivity analysis system for cancer diagnosis based on clinical data

Yun

Hwang

Anh

et al. 2015

BME

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“…The immunohistochemical detection for the nuclear expression of TTF-1 is considered as a useful marker in favor of lung or thyroid origin because of its high specificity (95-100%). [9][10][11][12] In the literature, TTF-1 expression in nuclei has been shown in rare cases of adenocarcinomas arising outside from lung or thyroid: one weakly positive case of metastatic ovarian carcinoma 13 and one focal positive case of endometrial carcinoma. 14 Recently, our group has shown one positive adenocarcinoma of colorectal origins, 8 whereas no such positivity was reported in literature ( Table 2).…”

Section: Discussionmentioning

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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“…6,[19][20][21][22][23] TTF-1 positivity has also been reported in 2 of 27 ependymomas arising in the third ventricle, 24 4 of 5 invasive ductal carcinomas of the breast, 25 1 of 66 gastric cancers, 12 4 of 41 colorectal adenocarcinomas, 26 and 4 of 7 colonic adenocarcinomas. 27 In the gynecologic tract, TTF-1 expression has been noted in 2 of 166 ovarian carcinomas (1 mixed serous and endometrioid adenocarcinoma and 1 serous carcinoma) in a tissue microarray study, 10 1 of 16 ovarian cancers (cell block of cytology fluid), 11 1 of 8 endometrial cancers, 12 and 1 of 14 primary peritoneal serous carcinomas. 13 In a previous study, we identified TTF-1 immunoreactivity in 1 of 28 (4%) endocervical adenocarcinomas, 6 of 32 (19%) endometrial endometrioid adenocarcinomas, and 3 of 13 (23%) endometrial serous carcinomas.…”

Section: Ttf-1 In Ovarian Neoplasmsmentioning

confidence: 99%

“…Expression of TTF-1 has also been reported in tumors other than those originating in the lung or thyroid; however, this marker has only been studied in a few gynecologic neoplasms. [10][11][12][13] We have previously reported TTF-1 immunoreactivity in 4% (1/28) of endocervical adenocarcinomas, 16% (6/32) of endometrial endometrioid adenocarcinomas, and 23% (3/13) of endometrial serous carcinomas.…”

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confidence: 99%

Thyroid transcription factor-1 expression in ovarian epithelial neoplasms

et al. 2008

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Thyroid transcription factor-1 (TTF-1) protein expression is widely used in the diagnosis of lung and thyroid carcinomas. Although there have been reports of TTF-1 immunoreactivity in tumors other than those originating in the lung or the thyroid, the expression of this marker has been studied in only a limited number of ovarian neoplasms. Our study examines the incidence of TTF-1 expression in a variety of ovarian epithelial neoplasms. Tissue microarrays of 138 ovarian serous carcinomas, 65 endometrioid adenocarcinomas, 35 mucinous adenocarcinomas, 30 mucinous neoplasms of low malignant potential, and 10 clear cell carcinomas were stained with anti-TTF1-antibody. In addition, whole tissue sections of 19 serous carcinomas, 5 endometrioid adenocarcinomas, 7 mucinous adenocarcinomas, and 3 clear cell carcinomas were stained. In the tissue microarrays, TTF-1 nuclear expression was demonstrated in 2 of 65 (3%) of the endometrioid adenocarcinomas; no nuclear immunoreactivity was identified in the remaining ovarian neoplasms. In the whole tissue sections, TTF-1 nuclear staining was present in 7 of 19 (37%) serous carcinomas, 1 of 5 (20%) endometrioid adenocarcinomas, and 1 of 3 (33%) clear cell carcinomas. In most of the positive cases, staining was focal, but in one endometrioid adenocarcinoma in the tissue microarray and in one serous and one clear cell carcinoma in the whole tissue sections, there was diffuse positivity. Overall, there was nuclear staining in 0.7% of tumors in the tissue microarray and 26% in the whole tissue sections. Although TTF-1 nuclear expression is generally considered to be a relatively specific marker for lung and thyroid neoplasms, the occasional immunoreactivity of ovarian carcinomas should be considered in the evaluation of neoplasms of unknown primary origin. It should also be taken into consideration when evaluating adenocarcinomas involving the lung in patients with a history of a gynecologic malignancy.

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The Value of Thyroid Transcription Factor-1 in Cytologic Preparations as a Marker for Metastatic Adenocarcinoma of Lung Origin

Cited by 99 publications

References 11 publications

Development of biomarker positivity analysis system for cancer diagnosis based on clinical data

Development of biomarker positivity analysis system for cancer diagnosis based on clinical data

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

Thyroid transcription factor-1 expression in ovarian epithelial neoplasms

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