Immunocytochemical expression of tissue specific transcription factor-1 in lung carcinoma.

Loreto, Carla Di; Lauro, Vincenzo Di; Puglisi, Fabio; Damante, Giuseppe; Fabbro, Dora; Beltrami, Carlo Alberto

doi:10.1136/jcp.50.1.30

Cited by 142 publications

(94 citation statements)

References 7 publications

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“…Interestingly, PAX9, TTF-1, and NKX2-8 activation status correlates with the tissue subtype of non-small-cell lung cancer; the majority of the adenocarcinoma samples exhibit a high probability of PAX9 and TTF-1 activation (Fig. 2B) relative to the squamous cell carcinoma samples, in line with published reports that TTF-1 protein expression is higher in adenocarcinoma than in squamous cell carcinoma (18)(19)(20)(21). In contrast to TTF-1 and PAX9, NKX2-8 deregulation is more prominent in squamous cell carcinomas.…”

Section: Ttf-1 Nkx2-8 and Pax9 Activation Correlates With Molecularsupporting

confidence: 77%

Characterizing the developmental pathways TTF-1 , NKX2–8 , and PAX9 in lung cancer

Hsu

Acharya²,

Balakumaran³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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We investigated the clinical implications of lung developmental transcription factors ( TTF-1 , NKX2–8 , and PAX9 ) that we recently discovered as cooperating oncogenes activated by way of gene amplification at chromosome 14q13 in lung cancer. Using stable transfectants of human bronchial epithelial cells, RNA expression profiles (signatures) representing activation of the biological pathways defined by each of the 3 genes were determined and used to risk stratify a non-small-cell lung cancer (NSCLC) clinical data set consisting of 91 early stage tumors. Coactivation of the TTF-1 and NKX2–8 pathways identified a cluster of patients with poor survival, representing ≈20% of patients with early stage NSCLC, whereas activation of individual pathways did not reveal significant prognostic power. Importantly, the poor prognosis associated with coactivation of TTF-1 and NKX2–8 was validated in 2 other independent clinical data sets. Furthermore, lung cancer cell lines showing coactivation of the TTF-1 and NKX2–8 pathways were shown to exhibit resistance to cisplatin, the standard of care for the treatment of NSCLC. This suggests that the cohort of patients with coactivation of TTF-1 and NKX2–8 pathways appears to be resistant to standard cisplatin therapy, suggesting the need for alternative therapies in this cohort of high-risk patients.

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Section: Ttf-1 Nkx2-8 and Pax9 Activation Correlates With Molecularsupporting

confidence: 77%

Characterizing the developmental pathways TTF-1 , NKX2–8 , and PAX9 in lung cancer

Hsu

Acharya²,

Balakumaran³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…The 14q13.3 amplicon does not appear to be limited to a specific subtype of lung cancer. This is particularly intriguing in that Ttf1 protein is rarely detected in the SCC type of lung cancer based on multiple studies in the literature (21)(22)(23)(24). Consistent with the literature, in multiple squamous lung cancer cell lines (including the amplified H2170 cells), we have not been able to detect the protein expression of TTF1 by using a highly specific monoclonal antibody [clone 8G7G3/1 (25)] (Fig.…”

Section: The 14q133 Amplicon Contains Three Transcription Factor Genessupporting

confidence: 60%

Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer

Kendall

Liu

Bakleh

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

205

213

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We used high-resolution array analysis to discover a recurrent lung cancer amplicon located at 14q13.3. Low-level gain of this region was detected in 15% of lung cancer samples, and high-level amplification was detected in an additional 4% of samples. Highlevel focal amplification appears to be specific to lung cancers, because it was not detected in >500 samples of other tumor types. Mapping of the commonly amplified region revealed there are three genes in the core region, all of which encode transcription factors with either established lung developmental function (TTF1/ NKX2-1, NKX2-8) or potential lung developmental function (PAX9). All three genes were overexpressed to varying degrees in amplified samples, although TTF1/NKX2-1 was not expressed in the squamous cancer subtype, consistent with previous reports. Remarkably, overexpression of any pairwise combination of these genes showed pronounced synergy in promoting the proliferation of immortalized human lung epithelial cells. Analysis of human lung cancer cell lines by both RNAi and ectopic overexpression further substantiates an oncogenic role for these transcription factors. These results, taken together with previous reports of oncogenic alterations of transcription factors involved in lung development (p63, CEBPA), suggest genetic alterations that directly interfere with transcriptional networks normally regulating lung development may be a more common feature of lung cancer than previously realized.gene amplification ͉ lung development ͉ lung oncogene ͉ TTF1 NKX2-8 PAX9 ͉ lineage addiction

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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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Immunocytochemical expression of tissue specific transcription factor-1 in lung carcinoma.

Cited by 142 publications

References 7 publications

Characterizing the developmental pathways TTF-1 , NKX2–8 , and PAX9 in lung cancer

Characterizing the developmental pathways TTF-1 , NKX2–8 , and PAX9 in lung cancer

Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer

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

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