Berghmans T, Paesmans M, Mascaux C, et al. Thyroid transcription factor 1—a new prognostic factor in lung cancer: a meta-analysis

Department of Intensive Care and Thoracic Oncology, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, Belgium.
Annals of Oncology (Impact Factor: 7.04). 12/2006; 17(11):1673-6. DOI: 10.1093/annonc/mdl287
Source: PubMed


The aim of this study was to determine the prognostic role for survival of thyroid transcription factor 1 (TTF-1) in lung cancer.
Studies evaluating survival and TTF-1 in lung cancer patients, published until August 2005, were assessed with a methodological scoring system. The required data for estimation of individual hazard ratios (HRs) for survival were extracted from the publications and a combined HR was calculated.
We identified 10 eligible papers, all dealing with non-small-cell lung cancer (NSCLC). Eight were meta-analysed (evaluable studies). Seven studies included patients with local and/or locoregional diseases and three dealt only with adenocarcinoma. Median methodological quality score was 65.9% (range = 31.8%-70.5%). TTF-1 positivity was associated with statistically significant reduced or improved survival in one and four studies, respectively. Combined HR for the eight evaluable studies was 0.64 [95% confidence interval (CI) = 0.41-1.00]. In the subgroup of adenocarcinoma, the combined HR was 0.53 (95% CI = 0.29-0.95).
TTF-1 is a good prognostic factor for survival in NSCLC. Its effect appears also significant when the analysis is restricted to patients with adenocarcinoma. This study supports the fact that TTF-1 could be included in further prospective trials studying prognostic factors in NSCLC.

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    • "The prognostic value of TTF1 expression in lung cancer patients has been evaluated in several studies, incorporating mainly local or loco-regional stages; however, results were conflicting and no consensus has been reached (Zhan et al., 2013). Data from these studies was limited by small sample size, patient heterogeneity and different immune-histochemical techniques used to detect TTF1 (Saad et al., 2004; Berghmans et al., 2006). For example, in stage I NSCLC patients, no survival difference was associated with TTF1 expression in one study while longer median overall survival (OS) was demonstrated in another one (Pelosi et al., 2001; Anagnostou et al., 2009). "
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    ABSTRACT: The prognostic role of thyroid transcription factor-1 (TTF-1) expression in lung cancer has been assessed but with inconsistent results. The present study aimed to evaluate the prognostic value of TTF1 expression in advanced non-squamous non-small cell lung cancer (NSCLC). In this retrospective study, patients with stage IIIB-IV non-squamous NSCLC were enrolled. Progression free survival (PFS) and overall survival (OS) were assessed according to TTF1 expression status, age categories (≤60 vs >60 years), gender, performance status (PS) (0-2 vs 3-4), type of 1st line chemotherapy (pemetrexed containing vs others) and EGFR status. A total of 120 patients were included. In univariate analysis, PFS was improved in patients with PS 0-2 (7.0 vs 2.0 months, p=0.002) and those who received pemetrexed-containing chemotherapy (9.2 vs 5.8 months, p=0.004). OS was improved in female patients (23.0 vs 8.7 months, p<0.0001), PS 0-2 (14.4 vs 2.0 months, p<0.0001), those with pemetrexed-containing chemotherapy (17.0 vs 11.0 months, p=0.019), TTF1-positive (12.8 vs 5.8 months, p=0.011) and EGFR- mutant patients (23.0 vs 11.7 months, p=0.006). In multivariate analysis, male gender (HR=2.34, p=0.025) and non-pemetrexed containing therapy (HR=2.24, p=0.022) were independent predictors of worse PFS. Wild EGFR status (HR=2.49, p=0.015) and male gender (HR=2.78, p=0.008) were predictors of worse OS. Pemetrexed-containing therapy significantly improved PFS while OS was improved in EGFR mutant patients. Female patients had better PFS and OS. TTF1 expression was not a prognostic marker in advanced non-squamous NSCLC.
    Full-text · Article · Apr 2015 · Asian Pacific journal of cancer prevention: APJCP
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    • "Another relevant histological marker is the thyroid transcription factor-1 (TTF-1). The meta-analysis by Berghmans et al. showed that TTF-1 positivity was associated with a statistically significant longer survival in NSCLC: combined HR of eight studies was 0,64 and 0.53 in the adenocarcinoma subgroup [22]. We also found this impact of TTF-1 positivity both in univariate and multivariate analysis, with a MS of 15.4 months versus 6.45 months for negative TTF-1 patients (HR = 0.54), and believe that TTF-1 status is a reliable marker for survival. "
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    ABSTRACT: Background: In non-small cell lung cancer patients (NSCLC), median survival from the time patients develop bone metastasis is classically described being inferior to 6 months. We investigated the subcategory of patients having an inaugural skeletal-related-event revealing NSCLC. The purpose of this study was to assess the impact of bone involvement on overall survival and to determine biological and tumoral prognosis factors on OS and PFS. An analysis of the subgroup of solitary bone metastasis patients was also performed. Methods: In a population of 1208 lung cancer patients, 55 consecutive NSCLC patients revealed by inaugural bone metastasis and treated between 2003 and 2010, were retrospectively analysed. Survival was measured with a Kaplan-Meyer curve. Univariate and multivariate analysis were performed using the Stepwise Cox proportional hazard regression model. A p value of less than 0,05 was considered statistically significant. Results: Estimated incidence of revealing bone metastasis is 4,5% among newly diagnosed lung cancer patients. Median duration of skeletal symptoms before diagnosis was 3 months and revealing bone site was located on axial skeleton in 70% of the cases. Histology was adenocarcinoma (78%), with small primary tumors Tx-T1-2 accounting for 71% of patients. Rate of second SRE is 37%.Median overall survival was 8.15 months, IQR [5-16 months], mean survival 13.4 months, and PFS was 3.5 months. In multivariate analysis, variables significantly associated with shortened survival were advanced T stage (HR=2.8; p=0.004), weight loss>10% (HR=3.1; p=0.02), inaugural spinal epidural metastasis (HR 2.5; p=0.0036), elevated C-reactive protein (HR=4.3; p=0.002) and TTF-1 status (HR=2.42; p=0.004). Inaugural spinal epidural metastasis is a very strong adverse pronostic factor in these cases, with a 3 months median survival. Single bone metastasis patients showed prolonged survival of 14.2 months versus 7.6 months, only in univariate analysis (HR=0.42; p=0.0059). Conclusion: Prognosis of lung cancer patients with inaugural SRE remains pejorative. Accurately estimating the survival of this population is helpful for bone surgical decision-making at diagnosis. The trend for a higher proportion of adenocarcinoma in NSCLC patients should result with an increasing number of patients with inaugural SRE at diagnosis.
    Full-text · Article · Jun 2014 · BMC Cancer
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    • "Thyroid Transcription Factor-1(TTF-1), also known as Nkx2.1 or thyroid-specific enhancer-binding protein, regulates genes in the thyroid, lungs, and diencephalon during embryogenesis [1,2]. Thus, TTF-1 has been regarded as a reliable marker for tumors originating in lung or thyroid tissues. "
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    ABSTRACT: Background The differential diagnosis between primary and secondary breast cancers might be difficult, especially in poorly differentiated tumors. Thyroid Transcription Factor-1 (TTF-1) has been regarded as a reliable marker for lung or thyroid origin, with only occasional positive staining in other tumors. However, positive cases have recently been reported among primary breast carcinomas. Methods and results Here, we analyzed expression of TTF-1 protein (clone SPT24) by immunohistochemical staining of sections from paraffin embedded tumor samples in 247 primary breast cancers from the population-based Norwegian Breast Cancer Screening Program. Positive staining (weak or strong) was observed in 7 cases (2,8%). As novel observations, positivity was demonstrated more frequently in estrogen receptor negative cases (14,0% vs. 1,4%; p = 0,004), highly proliferative tumors (8,8% vs. 1,1%; p = 0,008), tumors with a basal-like phenotype by showing expression of CK5/6 and/or P-cadherin (11,1% vs. 1,4%; p = 0,01), and tumors with blood vessel invasion (9,7% vs. 1,9%; p = 0,04). Also, TTF-1 was associated with histological grade 3 tumors compared with grade 1 or 2 tumors (7,7% vs. 1,5%; p = 0,04) as well as lymph node positive cases (5,2% vs. 1,8%; p = 0,03). Conclusions Our population-based findings indicate that TTF-1 may be positive in approximately 3% of primary breast cancers, and positivity indicates an association with adverse prognostic factors. Virtual slides The virtual slide(s) for this article can be found here:
    Full-text · Article · May 2013 · Diagnostic Pathology
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