Expression of Thyroid Transcription Factor-1 in Normal and Neoplastic Lung Tissues

Nakamura, Nobuki; Miyagi, Eri; Murata, Shin‐ichi; Kawaoi, Akira; Katoh, Ryohei

doi:10.1097/01.mp.0000028572.44247.cf

Cited by 124 publications

(74 citation statements)

References 29 publications

(38 reference statements)

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“…[68][69][70] Subsequent investigations using the 8G7G3/1 monoclonal antibody, however, have shown that TTF-1 expression is usually absent in these tumors. 47,[71][72][73][74][75] In the present investigation, none of the squamous carcinomas of the lung or the mesotheliomas exhibited TTF-1 positivity. While these findings indicate that TTF-1 immunostaining is not useful in discriminating between these malignancies, it may have some utility in distinguishing squamous carcinomas from lung adenocarcinomas since this marker is often expressed in the latter tumors.…”

Section: Discussionmentioning

confidence: 81%

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

2006

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As both mesotheliomas and squamous carcinomas can present a wide variety of morphological patterns, they can on occasion be confused. Recently, some groups of investigators have called attention to the difficulties that sometimes exist in distinguishing between these malignancies and the need to define a panel of markers that can assist in reaching the correct diagnosis. The aim of the present study is to compare the value of the various immunohistochemical markers currently available for the diagnosis of mesothelioma and squamous carcinoma of the lung. A total of 30 epithelioid pleural mesotheliomas exhibiting a solid or predominantly solid pattern, and 30 nonkeratinizing squamous carcinomas of the lung were investigated for the expression of the following markers: podoplanin, calretinin, mesothelin, WT1, keratin 5/6, keratin 7, p63, carcinoembryonic antigen (CEA), MOC-31, Ber-EP4, B72.3, BG-8 (Lewis y ), leu-M1 (CD15), and thyroid transcription factor-1 (TTF-1). All 30 (100%) of the mesotheliomas reacted for calretinin, mesothelin and keratin 7, 93% each for podoplanin, WT1 and keratin 5/6, 13% for Ber-EP4, 7% each for p63, MOC-31 and BG-8, and 0% for B72.3, CEA, leu-M1 and TTF-1. All 30 (100%) of the squamous carcinomas were positive for p63 and keratin 5/6, 97% for MOC-31, 87% for Ber-EP4, 80% for BG-8, 77% for CEA, 57% for keratin 7, 40% for calretinin and B72.3, 30% for leu-M1, 27% for mesothelin, 15% for podoplanin, and 0% for WT 1 and TTF-1. After analyzing the results, it is concluded that from a practical point-of-view, a combination of two positive mesothelioma markers (WT1 and calretinin or mesothelin) with two negative mesothelioma markers (p63 and MOC-31) would allow the differential diagnosis to be established between epithelioid mesotheliomas and squamous carcinomas of the lung in nearly all instances.

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Section: Discussionmentioning

confidence: 81%

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

2006

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“…8 Others have also reported high frequencies (generally 485% of cases) of TTF-1 expression by pulmonary small cell carcinomas as well as many pulmonary adenocarcinomas. 9,[12][13][14][15][16][17][18][19] Interestingly, in two of our original cohort of cases, observation of TTF-1 staining, in combination with a lack of p63 and high molecular weight keratin staining, led to reconsideration of the diagnosis, additional mucicarmine and surfactant precursor protein B staining, and reclassification. TTF-1 is a transcription factor that is normally expressed in alveolar pneumocytes, Clara cells, ciliated respiratory epithelial cells, and basal cells of the lung, 9 and is also expressed in the thyroid and brain.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4][5][6] Recent studies suggest the potential utility of several newer antibodies including thyroid transcription factor-1 (TTF-1), p63, p16(INK4A) (p16), and high molecular weight keratin, to help differentiate between small cell carcinomas and non-small cell carcinomas. [7][8][9][10] In this study, we evaluated the utility of a panel of these antibodies for distinguishing between small cell carcinoma and poorly differentiated squamous cell carcinoma.…”

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confidence: 99%

Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach

et al. 2005

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Accurate morphologic distinction between small cell carcinoma and poorly differentiated squamous cell carcinoma has critical therapeutic significance, but can be limited by crush artifact, tumor necrosis, limited tumor representation, and overlapping morphologic features. We evaluated a panel of antibodies for their efficacy in distinguishing between these neoplasms. Formalin-fixed paraffin-embedded tissue sections of small cell carcinomas and poorly differentiated squamous cell carcinomas underwent immunohistochemical staining with antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A). Of 28 small cell carcinomas, 26 (93%) small cell carcinomas showed diffuse moderate or strong staining for thyroid transcription factor-1 with no staining for high molecular weight keratin and p63. In contrast, 27/28 (96%) poorly differentiated squamous cell carcinomas manifested opposite immunoreactivities, with diffuse moderate or strong staining for high molecular weight keratin and p63, and no or minimal staining for thyroid transcription factor-1. In two additional cases originally interpreted as small cell carcinoma, high molecular weight keratin highlighted small numbers of neoplastic large cells, leading to reclassification as combined small cell and nonsmall cell carcinomas. p16(INK4A) expression varied widely in poorly differentiated squamous cell carcinomas, but was consistently moderate or strong and diffuse in small cell carcinomas, and proved helpful in the two thyroid transcription factor-1-negative small cell carcinomas. This study demonstrates that a panel consisting of antibodies to thyroid transcription factor-1, p63, high molecular weight keratin, and p16(INK4A) is highly effective for distinguishing between small cell carcinoma and poorly differentiated squamous cell carcinoma. This panel also facilitates diagnosis of combined small cell and non-small cell carcinomas.

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“…10 It has been primarily used for distinguishing lung carcinomas, both primary and metastatic, from other carcinomas. MOC-31 is a membrane glycoprotein isolated from a lung small cell carcinoma cell line, which has been shown to stain most normal epithelium and the vast majority of carcinomas.…”

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confidence: 99%

Alternative epithelial markers in sarcomatoid carcinomas of the head and neck, lung, and bladder—p63, MOC-31, and TTF-1

2005

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Sarcomatoid carcinomas are rare malignancies which represent poorly differentiated epithelial tumors that may be difficult to recognize as such. While some cases may have obvious epithelial areas, the sarcomatoid areas are poorly distinguishable from true sarcoma at the light microscopic level and, by immunohistochemistry, often show only limited staining for traditional epithelial markers such as cytokeratin or epithelial membrane antigen. This can be particularly problematic for diagnosis on small biopsy specimens. We sought to assess the diagnostic utility of several immunohistochemical markers of epithelial differentiation including p63, MOC-31, and thyroid transcription factor-1 on sarcomatoid carcinomas of the head and neck (19 cases; 'spindle cell carcinomas'), lung (19 cases), and urinary bladder (11 cases). These results were compared to immunohistochemistry for the traditional epithelial markers pan-cytokeratin and epithelial membrane antigen. Staining for p63 showed the greatest diagnostic utility, positive in 63, 50, and 36% of head and neck, lung, and urinary bladder sarcomatoid carcinomas, respectively. p63 stains were positive in many cases where immunohistochemistry was negative for both pan-cytokeratin and epithelial membrane antigen. All three alternative markers were quite specific for epithelial differentiation, each staining less than 10% of the control group of 73 various primary and metastatic sarcomas, melanomas, and benign spindle cell lesions. In conclusion, immunostaining beyond traditional pan-cytokeratin and epithelial membrane antigen may have diagnostic utility in this context.

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Expression of Thyroid Transcription Factor-1 in Normal and Neoplastic Lung Tissues

Cited by 124 publications

References 29 publications

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

The diagnostic utility of immunohistochemistry in distinguishing between epithelioid mesotheliomas and squamous carcinomas of the lung: a comparative study

Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach

Alternative epithelial markers in sarcomatoid carcinomas of the head and neck, lung, and bladder—p63, MOC-31, and TTF-1

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