53BP1 expression and immunoscore are associated with the efficacy of neoadjuvant chemoradiotherapy for rectal cancer

Strahlenther Onkol. 2020 May;196(5):465-473. doi: 10.1007/s00066-019-01559-x. Epub 2019 Dec 11.

Abstract

Purpose: Considering the effects of P53 binding protein 1 (53BP1) expression and T lymphocyte infiltration density on tumor radiosensitivity, we investigated the relation of 53BP1 expression and immunoscore based on T lymphocyte infiltration density with the efficacy of neoadjuvant chemoradiotherapy (CRT) for rectal cancer.

Methods: Fifty-five patients with rectal cancer receiving neoadjuvant CRT followed by surgery were enrolled. The 53BP1 expression level and the density of CD3+, CD8+, and CD45RO+ T lymphocytes in the tumor tissues were examined by immunohistochemistry, and the relation of these findings to the rates of tumor regression, disease-free survival (DFS), and overall survival (OS) was analyzed.

Results: The levels of 53BP1 and the CD3/CD8 immunoscore were closely correlated with the response to CRT (p < 0.05), with an area under the receiver operating characteristic curve for CRT efficacy prediction of 0.626 and 0.717, respectively. Further survival analysis revealed that high 53BP1 expression effectively prolonged 2‑year DFS compared with low 53BP1 expression (87.5% [95%CI 77.3-97.7] vs. 53.3% [95%CI 28.1-78.6]; p < 0.05), while the effect of immunoscore on survival was restricted by the expression status of 53BP1. Cox multivariate analysis confirmed 53BP1 as an independent prognostic factor in DFS.

Conclusion: The pretreatment levels of 53BP1 and the immunoscore based on CD3+/CD8+ T cell infiltration density in tumor tissues are effective predictors for the CRT response, and 53BP1 has a more pronounced impact on prognosis.

Keywords: Immune scores; P53 binding protein 1; Radiation sensitivity; Rectal cancer; Tumor inflitrating T cells.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Chemoradiotherapy, Adjuvant*
  • Combined Modality Therapy
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Immunohistochemistry
  • Leukocyte Count
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Lymphocytes, Tumor-Infiltrating / radiation effects
  • Male
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Staging
  • Proctectomy
  • Radiation Tolerance
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / mortality
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / therapy*
  • Retrospective Studies
  • Survival Rate
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / pathology
  • T-Lymphocytes / radiation effects
  • Treatment Outcome
  • Tumor Suppressor p53-Binding Protein 1 / analysis
  • Tumor Suppressor p53-Binding Protein 1 / genetics*
  • Young Adult

Substances

  • TP53BP1 protein, human
  • Tumor Suppressor p53-Binding Protein 1