Franz Rödel1, Kerstin Steinhäuser2, Nina-Naomi Kreis2, Alexandra Friemel2, Daniel Martin3, Ulrike Wieland4, Margret Rave-Fränk5, Panagiotis Balermpas6, Emmanouil Fokas6, Frank Louwen2, Claus Rödel6, Juping Yuan7. 1. Department of Radiotherapy and Oncology, Goethe-University, Frankfurt, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK) partner site: Frankfurt/Mainz, Heidelberg, Germany. Electronic address: franz.roedel@kgu.de. 2. Department of Gynecology and Obstetrics, Goethe-University, Frankfurt, Germany. 3. Department of Radiotherapy and Oncology, Goethe-University, Frankfurt, Germany. 4. Institute of Virology, National Reference Centre for Papilloma- and Polyomaviruses, University of Cologne, Germany. 5. Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Germany. 6. Department of Radiotherapy and Oncology, Goethe-University, Frankfurt, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK) partner site: Frankfurt/Mainz, Heidelberg, Germany. 7. Department of Gynecology and Obstetrics, Goethe-University, Frankfurt, Germany. Electronic address: yuan@em.uni-frankfurt.de.
Abstract
BACKGROUND: RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signalling pathway and its deregulation is involved in the pathogenesis of several tumour entities. RITA's impact on the response of anal squamous cell carcinoma (SCC) to anticancer treatment, however, remains elusive. MATERIALS AND METHODS: In our retrospective study immunohistochemical evaluation of RITA was performed on 140 pre-treatment specimens and was correlated with clinical and histopathologic characteristics and clinical endpoints cumulative incidence of local control (LC), distant recurrence (DC), disease-free survival (DFS) and overall survival (OS). RESULTS: We observed significant inverse correlations between RITA expression and tumour grading, the levels of HPV-16 virus DNA load, CD8 (+) tumour infiltrating lymphocytes and programmed death protein (PD-1) immunostaining. In univariate analyses, elevated levels of RITA expression were predictive for decreased local control (p = 0.001), decreased distant control (p = 0.040), decreased disease free survival (p = 0.001) and overall survival (p < 0.0001), whereas in multivariate analyses RITA expression remained significant for decreased local control (p = 0.009), disease free survival (p = 0.032) and overall survival (p = 0.012). CONCLUSION: These data indicate that elevated levels of pretreatment RITA expression are correlated with unfavourable clinical outcome in anal carcinoma treated with concomitant chemoradiotherapy.
BACKGROUND:RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signalling pathway and its deregulation is involved in the pathogenesis of several tumour entities. RITA's impact on the response of anal squamous cell carcinoma (SCC) to anticancer treatment, however, remains elusive. MATERIALS AND METHODS: In our retrospective study immunohistochemical evaluation of RITA was performed on 140 pre-treatment specimens and was correlated with clinical and histopathologic characteristics and clinical endpoints cumulative incidence of local control (LC), distant recurrence (DC), disease-free survival (DFS) and overall survival (OS). RESULTS: We observed significant inverse correlations between RITA expression and tumour grading, the levels of HPV-16 virus DNA load, CD8 (+) tumour infiltrating lymphocytes and programmed death protein (PD-1) immunostaining. In univariate analyses, elevated levels of RITA expression were predictive for decreased local control (p = 0.001), decreased distant control (p = 0.040), decreased disease free survival (p = 0.001) and overall survival (p < 0.0001), whereas in multivariate analyses RITA expression remained significant for decreased local control (p = 0.009), disease free survival (p = 0.032) and overall survival (p = 0.012). CONCLUSION: These data indicate that elevated levels of pretreatment RITA expression are correlated with unfavourable clinical outcome in anal carcinoma treated with concomitant chemoradiotherapy.
Authors: Alexandra Gilbert; Ane L Appelt; Stelios Theophanous; Robert Samuel; John Lilley; Ann Henry; David Sebag-Montefiore Journal: BMC Cancer Date: 2022-06-03 Impact factor: 4.638
Authors: Julia Maria Wildner; Alexandra Friemel; Lukas Jennewein; Susanne Roth; Andreas Ritter; Cornelia Schüttler; Qi Chen; Frank Louwen; Juping Yuan; Nina-Naomi Kreis Journal: Cells Date: 2019-11-21 Impact factor: 6.600
Authors: Bahir H Chamseddin; Eunice E Lee; Jiwoong Kim; Xiaowei Zhan; Rong Yang; Kathleen M Murphy; Cheryl Lewis; Gregory A Hosler; Suntrea T Hammer; Richard C Wang Journal: Oncotarget Date: 2019-10-15