Prognostic significance of <scp>WNT</scp> and hedgehog pathway activation markers in cancer of unknown primary

Fotopoulos, George; Gousia, Anna; Bareta, Eleni; Koumpis, Epameinondas; Chrisafi, Sofia; Bobos, Mattheos; Malamou‐Mitsi, Vassiliki; Fountzilas, George; Pavlidis, Nicholas; Pentheroudakis, George

doi:10.1111/eci.12518

Cited by 4 publications

(3 citation statements)

References 32 publications

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“…A cut off of 10% was taken. In particular, if >10% of all tumor cells were positive the sample was counted as positive for protein expression [19]. The mean immunoreactive score was generated from the 3 separate samples per patient.…”

Section: Methodsmentioning

confidence: 99%

Impact of Sonic Hedgehog Pathway Expression on Outcome in HPV Negative Head and Neck Carcinoma Patients after Surgery and Adjuvant Radiotherapy

et al. 2016

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IntroductionHPV positive patients suffering from head and neck cancer benefit from intensified radiotherapy when applied as a primary as well as an adjuvant treatment strategy. However, HPV negative patients treated with surgery and adjuvant radiotherapy lack validated prognostic biomarkers. It is therefore important to define prognostic biomarkers in this particular patient population. Especially, ´high-risk groups´ need to be defined in order to adapt treatment protocols. Since dysregulation of the sonic hedgehog pathway plays an important role in carcinogenesis, we aimed to assess whether members of the sonic hedgehog-signaling pathway may act as prognostic factors in patients with HPV negative head and neck squamous cell carcinoma.Materials and MethodsIn this prospective study, pretreatment tumor biopsies of patients with head and neck squamous cell carcinoma were taken during panendoscopy (2005 to 2008). All patients were treated with surgery and postoperative radiotherapy. After assessment of HPV and p16 status, protein expression profiles of the Sonic hedgehog-signaling pathway were determined by immunohistochemistry and tissue microarray analyses in 36 HPV negative tumor biopsies. Expression profiles of Sonic hedgehog, Indian hedgehog, Patched, Smoothened, Gli-1, Gli-2 and Gli-3 were correlated with patients´ clinical data, local-control rate, disease-free as well as overall survival. Data from The Cancer Genome Atlas databank were used for external validation of our results.ResultsGli-1 (p = 0.04) and Gli-2 (p = 0.02) overexpression was significantly linked to improved overall survival of HPV negative patients. Gli-2 (p = 0.04) overexpression correlated significantly with prolonged disease-free survival. Cox-multivariate analysis showed that overexpression of Gli-2 correlated independently (HR 0.40, 95% CI 0.16–0.95, p = 0.03) with increased overall survival.DiscussionGli-1 and Gli-2 overexpression represents a substantial prognostic factor for overall and disease-free survival in patients with locally advanced HPV negative head and neck cancer undergoing surgery and postoperative radiotherapy.

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Section: Methodsmentioning

confidence: 99%

Impact of Sonic Hedgehog Pathway Expression on Outcome in HPV Negative Head and Neck Carcinoma Patients after Surgery and Adjuvant Radiotherapy

et al. 2016

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The 2017 ESCI Award for the Best Clinical Research Article goes to the study by Christopher Adlbrecht and co-workers, entitled 'Outcome of conservative management vs. assist device implantation in patients with advanced refractory heart failure' [1]. This article was selected among seven finalist articles of outstanding quality and scientific impact [2][3][4][5][6][7].Although cardiac transplantation is recommended in terms of lasting clinical outcomes in patients with advanced refractory heart failure (HF) [8], the lack of organ donors and the ineligibility of some patients imply the need for improving alternative medical and surgical therapeutic strategies.In this retrospective study, the authors assessed clinical outcomes at 24-month follow-up of conservatively vs. surgically treated patients with refractory heart failure (HF) at the Medical University of Vienna. Of the 118 patients enrolled, 50 (42%) were conservatively managed using optimized medical therapy (OMT), while 69 (58%) were treated with the implantation of a ventricular assist device (VAD).

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confidence: 99%

“…The 2017 ESCI Award for the Best Clinical Research Article goes to the study by Christopher Adlbrecht and co-workers, entitled 'Outcome of conservative management vs. assist device implantation in patients with advanced refractory heart failure' [1]. This article was selected among seven finalist articles of outstanding quality and scientific impact [2][3][4][5][6][7].…”

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confidence: 99%

Advanced refractory heart failure: conservative or interventional approach?

Rigamonti

Montecucco

Liberale

2016

Eur J Clin Investigation

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The 2017 ESCI Award for the Best Clinical Research Article goes to the study by Christopher Adlbrecht and co-workers, entitled "Outcome of conservative management vs. assist device implantation in patients with advanced refractory heart failure" [1]. This article was selected among seven finalist articles of outstanding quality and scientific impact [2-7]. This article is protected by copyright. All rights reserved

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Exploring the biological hallmarks of cancer of unknown primary: where do we stand today?

2020

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Cancer of unknown primary (CUP) affects a small percentage of the general population. Nonetheless, a substantial number of these patients have a poor prognosis and consequently succumb to their illness within a year of diagnosis. The natural history of CUP is characterised by early metastasis from the unknown primary site, aggressive course and resistance to conventional chemotherapy. Unfortunately, the processes by which this orphan disease originates and progresses have not been fully elucidated and its biology remain unclear. Despite the conceptual progress in genetic and molecular profiling made over the past decade, recognition of the genetic and molecular abnormalities involved in CUP, as well as the identification of the tissue of origin remain unresolved issues. This review will outline the biology of CUP by exploring the hallmarks of cancer in order to rationalise the complexities of this enigmatic syndrome. This approach will help the reader to understand where research efforts currently stand and the pitfalls of this quest.

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Prognostic significance of WNT and hedgehog pathway activation markers in cancer of unknown primary

Abstract: Activation of the Wnt pathway was a positive prognostic factor in a small CUP series, possibly via enhanced chemosensitivity. Independent validation is warranted.

Cited by 4 publications

References 32 publications

Impact of Sonic Hedgehog Pathway Expression on Outcome in HPV Negative Head and Neck Carcinoma Patients after Surgery and Adjuvant Radiotherapy

Impact of Sonic Hedgehog Pathway Expression on Outcome in HPV Negative Head and Neck Carcinoma Patients after Surgery and Adjuvant Radiotherapy

Advanced refractory heart failure: conservative or interventional approach?

Exploring the biological hallmarks of cancer of unknown primary: where do we stand today?

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