Prognostic impact of TTF-1 expression in patients with stage IV lung adenocarcinomas

Schilsky, Juliana; Ni, Andy; Ahn, Linda S.; Datta, Sutirtha; Travis, William D.; Kris, Mark G.; Chaft, Jamie E.; Rekhtman, Natasha; Hellmann, Matthew D.

doi:10.1016/j.lungcan.2017.03.015

Cited by 55 publications

(59 citation statements)

References 34 publications

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“…Unlike a previous report conducted on a cohort of Asian patients that suggested that ROR1 overexpression is induced by TTF-1, [13] we did not nd any correlation between ROR1 mRNA levels and TTF-1 expression. Furthermore, in contrast to previously reports, [31][32][33] in our patient cohort TTF-1 expression was not prognostic for survival, although we acknowledge that this result could be biased by the low number of patients that we analyzed.…”

Section: Discussioncontrasting

confidence: 99%

Functional and Clinical Significance of ROR1 in Lung Adenocarcinoma

Schiavone

Epistolio

Vittoria

et al. 2020

Preprint

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BACKGROUND: Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is normally detectable in embryonic tissues and absent in adult tissues. ROR1 was shown to inhibit apoptosis, potentiate EGFR signaling and reported to be overexpressed and associated with poor prognosis in several tumor models. This study aimed to assess the expression of ROR1 and verify its prognostic significance in lung adenocarcinoma (AC) patients.METHODS: We analyzed ROR1 expression by quantitative real-time PCR (qRT-PCR) in 56 histologically confirmed lung AC, stage I to IV, in addition we evaluated its association with TTF-1 (thyroid transcription factor-1) expression and the main molecular alterations involved in lung cancerogenesis.RESULTS: ROR1 overexpression was observed in 28.6% of the entire cohort, using a cut-off of 1, or in 51.8% of the cases using the median value as threshold. Among patients without any genetic alteration, ROR1 overexpression was observed in 34.8% considering a cut-off of 1 and 52.2% considering the median value. The distribution of ROR1 was homogeneous among the different molecular categories: we found no association of ROR1 expression and the presence of gene mutations/rearrangements or the expression of TTF-1. Furthermore, ROR1 expression was not correlated with overall survival (OS).CONCLUSIONS: ROR1 overexpression could constitute a potential therapeutic target because altered in a consistent number of lung AC, especially in cases without druggable genetic alterations. ROR1 expression is independent of classical lung cancer molecular alterations and not correlated, in a Caucasian cohort, to TTF-1 expression. Finally, ROR1 expression does not play a prognostic significance.

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Section: Discussioncontrasting

confidence: 99%

Functional and Clinical Significance of ROR1 in Lung Adenocarcinoma

Schiavone

Epistolio

Vittoria

et al. 2020

Preprint

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“…Consistent with previous studies, cases with pulmonary NMC mainly expressed keratin, P63, and/or P40 in IHC, which suggests that NMC cells are derived from squamous cell carcinoma 9,25,26 . Two patients (Cases 2 and 7) were positive for TTF-1 expression, which favoured the diagnosis of lung adenocarcinoma 27 . The signi cance of TTF-1 expression in this entity is unclear.…”

Section: Discussionmentioning

confidence: 93%

Clinical features, treatment, and survival outcome of primary pulmonary NUT midline carcinoma

Xie

Wang

Qin

et al. 2020

Preprint

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Objective: NUT midline carcinoma (NMC), a rare type of squamous cell carcinoma, is genetically characterised by NUT midline carcinoma family member 1 (NUTM1) gene rearrangement. NMC can arise from the lungs; however, there is no standard for the management of primary pulmonary NMC. This study aimed to confirm the clinical features and report the treatments, especially with immune checkpoint inhibitors (ICIs), and outcomes of patients with primary pulmonary NMC. Methods: A retrospective review of patients with primary pulmonary NMC was performed in the First Affiliated Hospital of Guangzhou Medical University between January 2015 and December 2018. Clinical manifestations as well as radiographic and pathological findings were recorded. Whole-exome sequencing (WES), a predictor for ICI response, was used to determine the tumour mutational burden (TMB). Treatments, especially by immune checkpoint blockade, and patient survival were analysed.Results: Seven patients with primary pulmonary mass (four men and three women) with a mean age of 42 years (range, 23–74) who were diagnosed with NMC according to NUT immunohistochemistry staining were included for analysis. One patient had a rare fusion of CHRM5-NUTM1 by tumour sequencing. A wide range of TMB (1.75–73.81 mutations/Mbp) was observed. The initial treatments included chemotherapy (5/7, 71.4%), surgery (1/7, 14.3%), and radiotherapy (1/7, 14.3%). Five patients (5/7, 71.4%) received ICIs (programmed cell death protein 1 [PD1]/programmed cell death ligand 1 [PDL1] monoclonal antibody) as second- or higher-line treatments. The median overall survival (OS) was 4.1 months (range, 1.5–26.7 months). Conclusions: Patients with primary pulmonary NMC have a poor prognosis and chemotherapy is often preferred. Checkpoint immunotherapy is a good option as the second- or higher-line treatment. TMB seems to be not associated with OS.

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“…While Puglisi et al observed a detrimental effect of TTF-1 expression in resected NSCLC 11 , the relationship between TTF-1 and survival was not found in other observational studies 12 , 14 , 16 - 19 , 23 , 27 , 31 , 32 , 37 . However, others investigators reported that TTF-1 positivity was associated with a better prognosis 13 , 15 , 20 - 22 , 25 , 26 , 28 - 30 , 33 - 36 , 38 . These discrepant results indicate that the prognostic significance of TTF-1 in NSCLC remains controversial.…”

Section: Introductionmentioning

confidence: 94%

“…Although the role of TTF-1 as a marker for ADC in the differential diagnosis of primary lung cancers has been well documented, its prognostic significance in patients with NSCLC has still been inconclusive 11 - 36 . While Puglisi et al observed a detrimental effect of TTF-1 expression in resected NSCLC 11 , the relationship between TTF-1 and survival was not found in other observational studies 12 , 14 , 16 - 19 , 23 , 27 , 31 , 32 , 37 .…”

Section: Introductionmentioning

confidence: 99%

Prognostic Impact of TTF-1 Expression in Non-Squamous Non-Small-Cell Lung Cancer: A Meta-Analysis

Kim¹,

Kim²,

Kim³

et al. 2018

J. Cancer

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Thyroid transcription factor-1 (TTF-1) is overexpressed in up to 95% of primary lung adenocarcinoma while negative for almost all squamous cell carcinomas. TTF-1 expression has been investigated as a prognostic factor in non-small-cell lung cancer (NSCLC) with conflicting results. We conducted this meta-analysis to gain a better insight into the prognostic role of TTF-1 in patients only with non-squamous (non-SQ) NSCLC. A systematic computerized search of the electronic databases including PubMed, PMC, EMBASE, Web of Science, and Cochrane Library was performed. From 21 studies, 6,451 patients were included in the combined analysis of hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival. Compared with patients with non-SQ NSCLC showing negative TTF-1 expression, those with tumors harboring TTF-1 overexpression had significantly better survival (HR = 0.49, 95% CI: 0.42-0.57, p < 0.00001). Subgroup analyses revealed that TTF-1 expression significantly correlated with a better prognosis in stage I (HR = 0.65, 95% CI: 0.50-0.84, p = 0.0008) as well as stage III-IV non-SQ NSCLC (HR = 0.38, 95% CI: 0.29-0.49, p < 0.00001). In conclusion, this meta-analysis demonstrates that TTF-1 overexpression is a favorable prognostic factor in patients with non-SQ NSCLC. The subgroup analyses indicate that TTF-1 is a good prognostic marker for survival not only in early-stage but also in advanced non-SQ NSCLC.

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Prognostic impact of TTF-1 expression in patients with stage IV lung adenocarcinomas

Cited by 55 publications

References 34 publications

Functional and Clinical Significance of ROR1 in Lung Adenocarcinoma

Functional and Clinical Significance of ROR1 in Lung Adenocarcinoma

Clinical features, treatment, and survival outcome of primary pulmonary NUT midline carcinoma

Prognostic Impact of TTF-1 Expression in Non-Squamous Non-Small-Cell Lung Cancer: A Meta-Analysis

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