Mark Jakob1,2, Kariem Sharaf3, Markus Schirmer4, Martin Leu4, Stefan Küffer5, Mattis Bertlich6, Friedrich Ihler6,7, Frank Haubner6, Martin Canis6, Julia Kitz5. 1. Department of Otolaryngology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany. Mark.Jakob@med.uni-muenchen.de. 2. Department of Otolaryngology, University Medical Center Göttingen, Göttingen, Germany. Mark.Jakob@med.uni-muenchen.de. 3. Department of Otolaryngology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany. Kariem.Sharaf@med.uni-muenchen.de. 4. Department of Radiation Oncology, University Medical Center Göttingen, Göttingen, Germany. 5. Department of Pathology, University Medical Center Göttingen, Göttingen, Germany. 6. Department of Otolaryngology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany. 7. German Center of Vertigo and Dizziness, University Hospital, LMU Munich, Munich, Germany.
Abstract
PURPOSE: Cancer stem cells (CSCs) are held accountable for the progress of head and neck squamous cell carcinoma (HNSCC). In the presented study, the authors evaluated the prognostic value of CSC markers in two particular HNSCC cohorts. METHODS: This two cohort study consisted of 85 patients with advanced stage HNSCC, treated with primary radio(chemo)therapy (pRCT), and 95 patients with HNSCC, treated with surgery and partially adjuvant radio(chemo)therapy. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were assessed. Samples were assessed for the expression of different molecular stem cell markers (ALDH1, BCL11B, BMI‑1, and CD44). RESULTS: In the pRCT cohort, none of the baseline patient and tumor features exhibited a statistically significant relation with survival in either the cohort or the human papillomavirus (HPV)-stratified subcohorts. High expression of BMI‑1 significantly decreased OS and DFS, while high expression of CD44 decreased all modes of survival. Multivariate analysis showed significant prognostic influence for all tested CSC markers, with high BMI‑1 and CD44 decreasing survival (BMI-1: OS, DFS, DSS; CD44: OS, DFS) and high ALDH1 and BCL11B showing a beneficial effect on survival (ALDH1: OS, DFS; BCL11B: OS, DSS). In the surgical cohort, classical prognosticators such as HPV status, R1 resection, and nodal status in HPV-negative HNSCC played a significant role, but the tested CSC markers showed no significant effect on prognosis. CONCLUSION: Although validation in independent cohorts is still needed, testing for CSC markers in patients with advanced or late stage HNSCC might be beneficial, especially if many comorbidities exist or disease is irresectable. The findings might guide the development and earlier use of targeted therapies in the future.
PURPOSE:Cancer stem cells (CSCs) are held accountable for the progress of head and neck squamous cell carcinoma (HNSCC). In the presented study, the authors evaluated the prognostic value of CSC markers in two particular HNSCC cohorts. METHODS: This two cohort study consisted of 85 patients with advanced stage HNSCC, treated with primary radio(chemo)therapy (pRCT), and 95 patients with HNSCC, treated with surgery and partially adjuvant radio(chemo)therapy. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were assessed. Samples were assessed for the expression of different molecular stem cell markers (ALDH1, BCL11B, BMI‑1, and CD44). RESULTS: In the pRCT cohort, none of the baseline patient and tumor features exhibited a statistically significant relation with survival in either the cohort or the human papillomavirus (HPV)-stratified subcohorts. High expression of BMI‑1 significantly decreased OS and DFS, while high expression of CD44 decreased all modes of survival. Multivariate analysis showed significant prognostic influence for all tested CSC markers, with high BMI‑1 and CD44 decreasing survival (BMI-1: OS, DFS, DSS; CD44: OS, DFS) and high ALDH1 and BCL11B showing a beneficial effect on survival (ALDH1: OS, DFS; BCL11B: OS, DSS). In the surgical cohort, classical prognosticators such as HPV status, R1 resection, and nodal status in HPV-negative HNSCC played a significant role, but the tested CSC markers showed no significant effect on prognosis. CONCLUSION: Although validation in independent cohorts is still needed, testing for CSC markers in patients with advanced or late stage HNSCC might be beneficial, especially if many comorbidities exist or disease is irresectable. The findings might guide the development and earlier use of targeted therapies in the future.
Entities:
Keywords:
Head and neck cancer; Molecular markers; Primary radiochemotherapy; Surgical treatment; Survival
Authors: Juan P Rodrigo; Carlos Suárez; Alfio Ferlito; Kenneth O Devaney; Guy J Petruzzelli; Alessandra Rinaldo Journal: Acta Otolaryngol Date: 2003-01 Impact factor: 1.494
Authors: Marie Lundberg; Suvi Renkonen; Caj Haglund; Petri S Mattila; Ilmo Leivo; Jaana Hagström; Antti A Mäkitie Journal: Acta Otolaryngol Date: 2016-01-12 Impact factor: 1.494
Authors: Paul Reid; Loredana G Marcu; Ian Olver; Leyla Moghaddasi; Alexander H Staudacher; Eva Bezak Journal: Radiother Oncol Date: 2019-03-06 Impact factor: 6.280
Authors: Laura C Hildebrand; Ana L Carvalho; Isabel S Lauxen; Jacques E Nör; Carlos T S Cerski; Manoel Sant'Ana Filho Journal: J Oral Pathol Med Date: 2014-02-17 Impact factor: 4.253
Authors: Carolina Nör; Zhaocheng Zhang; Kristy A Warner; Lisiane Bernardi; Fernanda Visioli; Joseph I Helman; Rafael Roesler; Jacques E Nör Journal: Neoplasia Date: 2014-02 Impact factor: 5.715
Authors: Jan Budczies; Frederick Klauschen; Bruno V Sinn; Balázs Győrffy; Wolfgang D Schmitt; Silvia Darb-Esfahani; Carsten Denkert Journal: PLoS One Date: 2012-12-14 Impact factor: 3.240
Authors: Kariem Sharaf; Axel Lechner; Stefan P Haider; Robert Wiebringhaus; Christoph Walz; Gisela Kranz; Martin Canis; Frank Haubner; Olivier Gires; Philipp Baumeister Journal: Curr Oncol Date: 2021-07-19 Impact factor: 3.677