Immunohistochemical Study of Thyroid Transcription Factor-1 and HER2/ neu in Non–Small Cell Lung Cancer: Strong Thyroid Transcription Factor-1 Expression Predicts Better Survival

Haque, Abida K.; Syed, Salahuddin; Lele, Subodh M.; Freeman, Daniel; Adegboyega, Patrick A.

doi:10.1097/00129039-200206000-00002

Cited by 46 publications

(53 citation statements)

References 29 publications

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“…Intriguingly, in this present study, simultaneous activation of TTF-1 and NKX2-8 pathways was associated with poor survival, in contrast to activation of individual genes that did not have prognostic significance. This finding not only echoes our thesis of multiple collaborating driver genes at the 14q13.3 amplicon, but also potentially sheds light on the prognostic value of TTF-1 protein expression, which has thus far been controversial (9,33,34). We believe that the prognostic relevance of TTF-1 is best evaluated with consideration of its oncogenic collaborator, NKX2-8.…”

Section: Discussionsupporting

confidence: 80%

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: Discussionsupporting

confidence: 80%

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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“…A positive TTF1 staining has been inversely related to the proliferative activity evaluated through Ki-67 expression, usually considered as a marker of poor prognosis in NSCLC (Pelosi et al, 2001;Myong, 2003). On the other hand, a correlation between positive TTF1 staining and various molecular markers expression such as p53 or HER2/neu involved in lung carcinogenesis has been suggested (Haque et al, 2002;Yatabe et al, 2002;Myong, 2003). Thus, further biological investigations are needed.…”

Section: Discussionmentioning

confidence: 99%

“…A study on 222 stage I NSCLC patients demonstrated no survival difference associated with TTF1 immunoreactivity (Pelosi et al, 2001), while another study correlated a positive TTF1 staining of resected NSCLC with a poor survival (Puglisi et al, 1999). On the other hand, four studies on early stages of NSCLC associated a positive TTF1 staining with a longer survival (Haque et al, 2002;Myong, 2003;Tan et al, 2003;Saad et al, 2004). However, all these studies were interested in surgical NSCLC patients and all but one (Saad et al, 2004) included both ADC and non-ADC histological types of NSCLC.…”

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confidence: 99%

Positive thyroid transcription factor 1 staining strongly correlates with survival of patients with adenocarcinoma of the lung

et al. 2005

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This study investigated the relation between positive thyroid transcription factor 1 (TTF1) staining and survival of patients affected by primary adenocarcinoma (ADC) of the lung. Pathological tissue from consecutive ADC patients was collected from 2002 to 2004. The anti-TTF1 antibody (8G7G3/1, dilution of 1/200) was used. Thyroid transcription factor 1 staining was assessed for each tumour as positive or negative. Probability of survival was estimated by Kaplan -Meier and difference tested by log-rank test. A Cox's regression multivariate analysis was carried out. In all, 106 patients were studied (66% male, 69% PS0 -1, 83% with stage III or IV). Tumours expressed positive TTF1 staining in 66% of cases. Multivariate analysis demonstrated an independent lower risk of death for patients whose tumour expresses positive TTF1 staining (HR ¼ 0.51, 95% CI 0.30 -0.85; P ¼ 0.01) and higher grade of differentiation (HR ¼ 0.40, 95% CI 0.24 -0.68; P ¼ 0.001). In conclusion, positive TTF1 staining strongly and independently correlates with survival of patients with primary ADC of the lung.

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“…Among those, 68% of ADCs (51 of 75) were positive but only 21% of squamous cell carcinomas (9 of 43) were positive. In a previous study, the positive expression of Nkx2-1 was found in 25%-76% of ADC subtypes (Bejarano et al, 1995;Fabbro et al, 1996;Holzinger et al, 1996;di Loreto et al, 1997;Bohinski et al, 1998;di Loreto et al, 1998;Harlamert et al, 1998;Kaufmann and Dietel, 2000) and 0%-38% of SCCs (Kaufmann and Dietel, 2000;Ordonez, 2000c;Pelosi et al, 2001;Haque et al, 2002). Several studies have evaluated the expression of Nkx2-1 in SCLCs; however, whether this can be used as a specific marker for SCLC remains unclear (Ordonez, 2000c).…”

Section: Lung Cancer Expressionmentioning

confidence: 99%

Nkx2-1: a novel tumor biomarker of lung cancer

Lin

Ruan

et al. 2012

J. Zhejiang Univ. Sci. B

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Nkx2-1 (Nkx homeobox-1 gene), also known as TTF-1 (thyroid transcription factor-1), is a tissue-specific transcription factor of the thyroid, lung, and ventral forebrain. While it has been shown to play a critical role in lung development and lung cancer differentiation and morphogenesis, molecular mechanisms mediating Nkx2-1 cell-and tissue-specific expression in normal and cancerous lungs have yet to be fully elucidated. The recent identification of prognostic biomarkers in lung cancer, particularly in lung adenocarcinoma (ADC), and the different reactivity of patients to chemotherapeutic drugs have opened new avenues for evaluating patient survival and the development of novel effective therapeutic strategies. The function of Nkx2-1 as a proto-oncogene was recently characterized and the gene is implicated as a contributory factor in lung cancer development. In this review, we summarize the role of this transcription factor in the development, diagnosis, and prognosis of lung cancer in the hope of providing insights into the utility of Nkx2-1 as a novel biomarker of lung cancer.

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Immunohistochemical Study of Thyroid Transcription Factor-1 and HER2/ neu in Non–Small Cell Lung Cancer: Strong Thyroid Transcription Factor-1 Expression Predicts Better Survival

Cited by 46 publications

References 29 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

Positive thyroid transcription factor 1 staining strongly correlates with survival of patients with adenocarcinoma of the lung

Nkx2-1: a novel tumor biomarker of lung cancer

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