Analysis of the Immunoexpression of Opioid Receptors and their Correlation with Markers of Angiogenesis, Cell Proliferation and Apoptosis in Breast Cancer

Asian Pac J Cancer Prev. 2021 Feb 1;22(2):633-640. doi: 10.31557/APJCP.2021.22.2.633.

Abstract

Objective: Breast cancer is a disease of great concern. The prognosis of this tumor is related to its staging. Opioids are widely used to minimize pain in oncology clinics; however, the relationship between the administration of opioids and their effects on tumor cells has yet to be elucidated. Therefore, this study aimed to evaluate the immunoexpression of mu- (μ) and kappa- (κ) opioid receptors and their correlation with markers of angiogenesis, cell proliferation, and apoptosis in biopsies of breast tumors.

Methods: Demographic data, tumor characteristics, opioid use, and prognostic factors were collected from medical records. After the selection of the excisional biopsies, immunohistochemistry was performed for μ- and κ-opioid receptors, vascular endothelial growth factor (VEGF), Ki-67, and TUNEL.

Results: A significant predominance of Ki-67 and μ-opioid receptor immunoexpression in the lymph nodes was observed in patients administered opioid medications. The luminal A subtype showed higher apoptosis levels (TUNEL) compared to the luminal B subtype. Patients with T4 tumor who had recurrence demonstrated a reduced expression of κ-opioid receptors at the lymph node location. Correlation analyses between the μ and κ opioid markers, VEGF, Ki-67, and TUNEL showed that these findings are likely involved in the same mechanisms the cancer of T4 stage breast cancer.

Conclusion: The κ-opioid receptor has a lower immunoexpression in nodal tumor metastasis with recurrence, whereas the μ-opioid receptor is directly related to expression of TUNEL-positive cells in tumors and indirectly to Ki-67 in nodal metastasis. Neither of the two receptors was expressed in the primary tumor or nodal metastasis in relation to VEGF.

Keywords: Luminal A; Prognosis; kappa-opioide receptor; luminal B; mu-opioide receptor.

Publication types

  • Observational Study

MeSH terms

  • Apoptosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Cross-Sectional Studies
  • Female
  • Humans
  • Ki-67 Antigen / metabolism
  • Lymph Nodes / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Receptors, Opioid, kappa / metabolism*
  • Receptors, Opioid, mu / metabolism*
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Ki-67 Antigen
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu
  • Vascular Endothelial Growth Factor A