TTF-1 gene expression in human lung tumours

Fabbro, Dora; Loreto, Carla Di; Stamerra, O.; Beltrami, Carlo Alberto; Lonigro, Renata; Damante, Giuseppe

doi:10.1016/0959-8049(95)00560-9

Cited by 141 publications

(95 citation statements)

References 20 publications

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“…19 Although the current literature data indicate that TTF-1 is highly expressed in most types of lung adenocarcinomas, it has also been reported in a fraction of squamous carcinomas. [8][9][10] In our control cases, only two squamous carcinomas (10%) were positive for TTF-1, which was conversely expressed in a percentage of LCCs, as expected from the literature. Concerning markers usually associated with squamous-cell carcinoma differentiation, we did not find p63 to be specific enough of the squamous-cell population, and indeed several adenocarcinomas were also positive, as also recently reported.…”

Section: Discussionsupporting

confidence: 88%

“…7 Indeed, these markers are relatively sensitive, but not completely specific. A minor fraction of squamous carcinoma is reported to react with TTF-1, [8][9][10] although it is not clear whether these cases are pure squamous or rather combined adenosquamous cancers. On the other side, p63 is considered a marker of squamous epithelia, although recent reports indicate that this protein is also expressed in basal cells of glandular tumors.…”

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confidence: 99%

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Desmocollin-3: a new marker of squamous differentiation in undifferentiated large-cell carcinoma of the lung

et al. 2009

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Lung cancer classification in small-cell and non-small-cell types was recently challenged by data on the differential efficacy of new cytotoxic agents in specific histotypes. An accurate histotype definition has therefore gained interest in both preoperative and surgical materials, but is a hard task especially in undifferentiated large-cell tumors lacking morphological signs of squamous or glandular differentiation. The responsiveness of these latter subtypes to new drugs apparently more selective for adenocarcinomas or squamous carcinomas is not fully understood, also due to the heterogeneity of diagnostic criteria for this tumor entity. Current immunohistochemical markers are not fully specific and new molecules are to be explored. On the basis of gene expression profiling data, reporting a remarkable differential expression of desmocollin-3 (a protein localized in desmosomal junctions of stratified epithelial) between adeno-and squamous cancers, we immunostained 62 cases of resected undifferentiated large-cell lung carcinomas for desmocollin-3 (and for TTF-1, p63 and mucin stain), to test its ability to identify a (residual) squamous phenotype, if present. Desmocollin-3 was expressed in almost half of the undifferentiated large-cell cancers and was mutually exclusive with TTF-1 (positive in 39%; the remaining 18 % of cases was double negative). Special large-cell carcinoma variants expressed desmocollin-3 in 6 of 6 basaloid, 7 of 12 clear-cell types, again mutually exclusive with TTF-1 expression. None of seven sarcomatoid carcinomas reacted for either marker. In 31 cytological samples diagnosed as 'non-small-cell lung carcinoma', desmocollin-3 was again mutually exclusive with TTF-1 and stained all squamous carcinomas, 1 of 19 adenocarcinoma only, and 50% of large-cell carcinoma (all histologically confirmed). This combined morphophenotypic approach may represent a valid adjunct (for both surgical and cytological samples) in the selection of patients with lung cancer to medical treatments tailored according to different efficacy in different lung carcinomas of the squamous, adeno-and large-cell types. Modern Pathology ( Keywords: large-cell carcinoma; squamous differentiation; desmocollin-3; diagnosis Lung cancer is subdivided into four histotypes, including small-cell carcinoma (SCLC) on the one side, and carcinomas of squamous-, adeno-and large-cell types on the other. These latter tumor groups have different pathological features, but have generally been treated so far according to similar strategies, so that a clear-cut distinction among these types (except for SCLC) was not considered clinically relevant. 1 Indeed, the WHO classifications of lung carcinoma have always kept the different histological types separate and proposed individual categories for squamous carcinoma, adenocarcinoma and large-cell (anaplastic) carcinoma (LCC). 2 The latter category underwent major changes in the last classification scheme, 3 having undifferentiated pleomorphic and/or sarcomatoid variants been moved to a new group o...

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Section: Discussionsupporting

confidence: 88%

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confidence: 99%

Desmocollin-3: a new marker of squamous differentiation in undifferentiated large-cell carcinoma of the lung

et al. 2009

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“…In the present study, TTF-1 positivity was observed in 63% of BACs. Previous investigators have shown the frequency of TTF-1 staining in such tumors to range anywhere from 25-100%, though the number of cases in each particular series has been relatively small (3,6,7,9,10).…”

Section: Discussionmentioning

confidence: 92%

“…Previous immunohistochemical studies using antibodies against TTF-1 have demonstrated immunoreactivity in a variety of tumors of pulmonary origin (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Immunohistochemical positivity of bronchioloalveolar carcinomas (BACs) for TTF-1 has been well established, with such tumors addressed in most studies primarily as a subset of the general category of pulmonary adenocarcinomas (3,6,7,9,10). Expression of TTF-1 in the context of the mucinous and nonmucinous subtypes of BACs, however, has not been well described, though it has been suggested that mucinous pulmonary adenocarcinomas, including those of bronchioloalveolar type, tend to be TTF-1 negative (10).…”

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Expression of Thyroid Transcription Factor-1, Cytokeratin 7, and Cytokeratin 20 in Bronchioloalveolar Carcinomas: an Immunohistochemical Evaluation of 67 Cases

2002

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“…In some of the earlier studies, which used a polyclonal antibody against TTF-1, positivity for this protein was reported in 11-23% of the squamous carcinomas of the lung. [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.…”

Section: Discussionmentioning

confidence: 99%

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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TTF-1 gene expression in human lung tumours

Cited by 141 publications

References 20 publications

Desmocollin-3: a new marker of squamous differentiation in undifferentiated large-cell carcinoma of the lung

Desmocollin-3: a new marker of squamous differentiation in undifferentiated large-cell carcinoma of the lung

Expression of Thyroid Transcription Factor-1, Cytokeratin 7, and Cytokeratin 20 in Bronchioloalveolar Carcinomas: an Immunohistochemical Evaluation of 67 Cases

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

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