Differential expression of thyroid transcription factor 1 in small cell lung carcinoma and merkel cell tumor

Byrd-Gloster, Angela L.; Khoór, András; Glass, L. Frank; Messina, Jane L.; Whitsett, Jeffrey A.; Livingston, Sandra; Cagle, Philip T.

doi:10.1016/s0046-8177(00)80199-9

Cited by 129 publications

(74 citation statements)

References 15 publications

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“…36,37 A significant proportion of both entities, particularly small cell carcinoma of the lung, however, express neither CK7 nor CK20, ie, 57-82% of small cell carcinoma of the lung, and 12% of Merkel cell carcinoma, 36,37 and exceptions can occur such as Merkel cell carcinomas that are CK7( þ )/ CK20(À) 31,32 or CK7( þ )/CK20( þ ) 31 and such as small cell carcinomas of the lung that are CK7(À)/ CK20( þ ) or CK7( þ )/CK20( þ ). 33,37,38 TTF-1 is a sensitive and specific marker for small cell carcinoma of the lung, and it is expressed in approximately 80-90% of tumors. 7,[39][40][41][42][43][44][45] Currently a combination of CK20 and TTF-1 immunostains are used for the diagnosis of Merkel cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…[33][34][35] There are a few studies reporting TTF-1 expression in extrapulmonary small cell carcinoma by using monoclonal antibody of clone 8G7G3/1, 34,46-49 but no case of TTF-1-positive Merkel cell carcinoma has been reported to our knowledge. [33][34][35]38 One of our cases of Merkel cell carcinoma unequivocally expressed TTF-1. This case, along with other extrapulmonary small cell carcinomas reported in the literature, illustrates that TTF-1 can be aberrantly expressed by small cell carcinomas of a variety of locations for yet an unknown reason.…”

Section: Discussionmentioning

confidence: 99%

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MASH1: a useful marker in differentiating pulmonary small cell carcinoma from Merkel cell carcinoma

2008

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Merkel cell carcinoma is the cutaneous counterpart of small cell carcinoma, and the most important differential diagnosis is cutaneous metastasis of small cell carcinoma of the lung. There have been a handful of studies reporting on the utility of a variety of immunohistochemical markers that distinguish between the two entities. Achaete-scute complex-like 1 (MASH1, ASCL1) is important in the development of the brain and the diffuse neuroendocrine system including pulmonary neuroendocrine cells. A recent study, using a cDNA array, identified Mash1 as one of the best classifier genes to differentiate pulmonary small cell carcinoma from Merkel cell carcinoma. We immunohistochemically applied this finding to the diagnostic setting. A total of 30 cases of Merkel cell carcinoma and 59 cases of small cell carcinoma of the lung were immunostained with anti-MASH1 and TTF-1 antibodies. Of 59 small cell carcinomas, 49 (83%) expressed MASH1 in nuclear staining whereas out of 59 small cell carcinomas, 43 (73%) expressed TTF-1 in nuclear staining. MASH1 was completely negative in all 30 Merkel cell carcinomas whereas TTF-1 expression was seen in 1 of the 30 Merkel cell carcinomas (3%). MASH1 is a useful adjunct marker for differentiating small cell carcinoma of the lung from Merkel cell carcinoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MASH1: a useful marker in differentiating pulmonary small cell carcinoma from Merkel cell carcinoma

2008

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“…TTF-1 is expressed in 90-100% of small-cell lung carcinomas and is essentially not detected in poorly differentiated pulmonary squamous cell carcinomas. 2,3,16,17 In contrast, 90-100% of poorly differentiated pulmonary squamous cell carcinomas are immunoreactive with p63 antibody, while small-cell lung carcinomas do not express p63. 5,6 The combined use of TTF-1 and p63 antibodies on tissue and cell block sections showed that the TTF-1 þ /p63À phenotype is present in 87-94% of small-cell lung carcinomas, and the p63 þ /TTF-1À phenotype in 96-100% of poorly differentiated pulmonary squamous cell carcinomas.…”

Section: Discussionmentioning

confidence: 99%

TTF-1 and p63 for distinguishing pulmonary small-cell carcinoma from poorly differentiated squamous cell carcinoma in previously pap-stained cytologic material

2006

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In histology and cell block sections, antibodies to thyroid transcription factor-1 (TTF-1) and p63 have been demonstrated to be useful markers for distinguishing between small-cell lung carcinoma and poorly differentiated pulmonary squamous cell carcinoma. In this study, we assessed the utility of TTF-1 and p63, as an antibody panel, for differentiating between these two neoplasms in previously Papanicolaou (Pap)-stained cytologic smears and cytospin slides. Twenty-six lung carcinomas (13 small-cell lung carcinomas, 13 poorly differentiated pulmonary squamous cell carcinomas) were evaluated. One or two previously 95% ethanol-fixed, Pap-stained smears or cytospin slides were selected from each case. The cytologic material from these slides was transferred to positively charged slides. Unstained recuts were obtained from the corresponding histologic specimens or cell blocks. Immunohistochemical staining for TTF-1 and p63 was performed on the paired samples from each tumor. All (13/13) small-cell lung carcinomas were negative for p63 and 92% (12/13) were positive for TTF-1. Conversely, all (13/13) poorly differentiated pulmonary squamous cell carcinomas expressed p63 and did not express TTF-1. Immunoreactivity for p63 was also noted in bronchial reserve cells and metaplastic squamous cells. The immunostaining results obtained from the cytology slides were concordant with those of the histology or cell block sections in all cases. The results of this study show that TTF-1 and p63 immunostaining can be successfully applied to previously Pap-stained cytologic material, as an antibody panel, to facilitate pathologic differentiation between small-cell lung carcinomas and poorly differentiated pulmonary squamous cell carcinomas. p63 immunostaining, however, must be interpreted in conjunction with cytomorphology to distinguish between poorly differentiated pulmonary squamous cell carcinomas and benign cellular constituents of the lung.

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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%

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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Differential expression of thyroid transcription factor 1 in small cell lung carcinoma and merkel cell tumor

Cited by 129 publications

References 15 publications

MASH1: a useful marker in differentiating pulmonary small cell carcinoma from Merkel cell carcinoma

MASH1: a useful marker in differentiating pulmonary small cell carcinoma from Merkel cell carcinoma

TTF-1 and p63 for distinguishing pulmonary small-cell carcinoma from poorly differentiated squamous cell carcinoma in previously pap-stained cytologic material

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

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