Prognostic impact of RITA expression in patients with anal squamous cell carcinoma treated with chemoradiotherapy

Radiother Oncol. 2018 Feb;126(2):214-221. doi: 10.1016/j.radonc.2017.10.028. Epub 2017 Nov 6.

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.

Keywords: Anal cancer; HPV-16; Prognostic marker; RITA.

MeSH terms

  • Anus Neoplasms / drug therapy
  • Anus Neoplasms / metabolism*
  • Anus Neoplasms / radiotherapy
  • Anus Neoplasms / therapy*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / radiotherapy
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy
  • DNA, Viral / analysis
  • DNA-Binding Proteins / biosynthesis*
  • Disease-Free Survival
  • Female
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 16 / isolation & purification
  • Humans
  • Immunohistochemistry
  • Lymphocytes, Tumor-Infiltrating
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / radiotherapy
  • Prognosis
  • Retrospective Studies

Substances

  • DNA, Viral
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • ZNF331 protein, human