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

Document Type: Research Articles

Authors

1 Department of Morphology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.

2 Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Fortaleza, Ceará, Brazil.

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.

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