The Prognostic Value of the Immunohistochemical Expression of Phosphorylated RB and p16 Proteins in Association with Cyclin D1 and the p53 Pathway in a Large Cohort of Patients with Breast Cancer Treated with Taxane-based Adjuvant Chemotherapy

Anticancer Res. 2017 Jun;37(6):2947-2957. doi: 10.21873/anticanres.11648.

Abstract

Background: The retinoblastoma (RB) gene is a tumor-suppressor gene that plays a central role in regulating the cell cycle. Inactivation of this gene is involved in breast cancer.

Patients and methods: A total of 827 patients with breast cancer treated with taxane-based adjuvant chemotherapy were included in the study. Protein expression of RB, phosphorylated RB (pRB), p16, cyclin D1 and p53 was evaluated by immunohistochemistry.

Results: Neither of the retinoblastoma markers (RB and pRB) reached statistical significance in terms of their association with disease-free or overall survival. Nevertheless, when clustering analysis was performed, patients with tumors featuring low levels of p16, cyclin D1 and p53 with concomitantly high levels of pRB had reduced risk for relapse (Wald's p=0.015).

Conclusion: The p53-mediated sensitivity of breast cancer cells to chemotherapeutic agents appears to be driven mostly by pRB. Using agents that enhance RB phosphorylation might possibly increase the chemosensitivity of breast cancer cells.

Keywords: breast cancer; chemotherapeutic agents; immunohistochemistry; p16; pRB.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Chemotherapy, Adjuvant
  • Cyclin D1 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Paclitaxel / therapeutic use
  • Phosphorylation
  • Prognosis
  • Retinoblastoma Protein / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*
  • Young Adult

Substances

  • Antineoplastic Agents, Phytogenic
  • CCND1 protein, human
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Retinoblastoma Protein
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cyclin D1
  • Paclitaxel