Prognostic value of circulating Bcl-2 and anti-p53 antibodies in patients with breast cancer: A long term follow-up (17.5 years)

Article type: Research Article

Authors: Sirotković-Skerlev, Maja^{a; e; *} | Plavetić, Natalija Dedić^{b; e} | Sedlić, Filip^{a; e} | Kuna, Sanja Kusačić^{c; e} | Vrbanec, Damir^d | Belev, Borislav^{b; e} | Pleština, Stjepko^{b; e} | Kovač, Zdenko^{a; e} | Kulić, Ana^a

Affiliations: [a] Department of Oncology, Division of Pathophysiology and Experimental Oncology, University Hospital Center Zagreb, Zagreb, Croatia | [b] Department of Oncology, Division of Medical Oncology, University Hospital Center Zagreb, Zagreb, Croatia | [c] Department of Nuclear Medicine and Radiation Protection, University Hospital Center Zagreb, Zagreb, Croatia | [d] Juraj Dobrila University of Pula, Pula, Croatia | [e] School of Medicine, University of Zagreb, Zagreb, Croatia

Correspondence: [*] Corresponding author: Maja Sirotković-Skerlev, Department of Oncology, Division of Pathophysiology and Experimental Oncology, University Hospital Center Zagreb, Kišpatićeva 12, HR-10 000 Zagreb, Croatia. Tel.: +385 91 466 7704; E-mail: majasirotkovic@gmail.com.

Abstract: BACKGROUND: Apoptosis inhibition is a major tumorigenic factor. Bcl-2 dysregulation and TP53 mutation status, which may correlate with autoantibody generation, contribute to impaired apoptosis. OBJECTIVE: This study aimed to investigate the prognostic value of circulating Bcl-2 and anti-p53 antibodies (p53Abs) in a 17.5-year follow-up of breast cancer patients. We also analyzed the correlations of Bcl-2 and p53Abs with various clinicopathological parameters in order to assess their impact on tumor aggressiveness. METHODS: Serum Bcl-2 and p53Abs levels were analyzed by the enzyme-linked immunosorbent assay (ELISA) in 82 patients with invasive breast cancer and twenty individuals without malignancy. RESULTS: Serum Bcl-2 and p53Abs levels in breast cancer patients were significantly higher than those in controls. Patients with high levels of Bcl-2 (cut-off 200 U/ml) had a poorer prognosis (17.5-year survival) than those with lower Bcl-2 values. In combined analysis the subgroup of patients with elevated p53Abs (cut-off 15 U/ml) and elevated Bcl-2 (cut-offs 124 U/ml and 200 U/ml) had the worse prognosis in 17.5-year survival. In correlation analysis p53Abs and Bcl-2 were associated with unfavorable clinicopathological parameters. CONCLUSIONS: Our results suggest that breast cancer patients with high serum levels of p53Abs and Bcl-2 present an especially unfavorable group in a long follow-up.

Keywords: Breast cancer, Bcl-2, anti-p53 antibodies, ELISA, survival

DOI: 10.3233/CBM-201497

Journal: Cancer Biomarkers, vol. 30, no. 1, pp. 95-104, 2021