Utility of surfactant protein B precursor and thyroid transcription factor 1 in differentiating adenocarcinoma of the lung from malignant mesothelioma

Khoór, András; Whitsett, Jeffrey A.; Stahlman, Mildred T.; Olson, Sandra J.; Cagle, Philip T.

doi:10.1016/s0046-8177(99)90096-5

Cited by 143 publications

(98 citation statements)

References 25 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: 89%

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: 89%

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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“…[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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“…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).…”

mentioning

confidence: 99%

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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Utility of surfactant protein B precursor and thyroid transcription factor 1 in differentiating adenocarcinoma of the lung from malignant mesothelioma

Cited by 143 publications

References 25 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

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

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

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