ANTIIDIOTYPIC AUTO-ANTIBODIES SPECIFIC TO STEROID HORMONES AND TUMOR PROLIFERATION IN BREAST CANCER PATIENTS

Abstract

Nongenomic effects of antibodies specific to membrane steroid receptors are well known. Auto-antibodies against estrogen-receptor (ER) were revealed in the blood serum of breast cancer patients (BCP). Their serum levels were correlated with tumor proliferation, detected with protein Ki-67. Purified antibodies stimulated the proliferation of cultivated tumor cells MCF-7 in vitro. Antiidiotypic antibodies against monoclonal antibodies, specific to estradiol, had the same agonist activity. However, the function of auto-antibodies against progesterone receptor (PR) remained unknown. The purpose of this study was to search association of serum antiidiotypic, specific to estradiol and progesterone (IgG2-E2 and IgG2-Pg) with tumor protein Ki-67 in BCP. The IgG2-E2 and IgG2-Pg were studied in 204 healthy women and 663 BCP with ER+/PR+ tumors by ELISA using adsorbed monoclonal antibodies against E2 and Pg. Ki-67, ER and Pg were detected by immunohistochemical methods. High levels of IgG2-E2 in BCP I stage were detected frequently than in healthy women (63.9% vs 40.2%, р<0.001), and frequently with tumor Ki-67>14, than with tumor Ki-67≤14 (63.9% vs 56.9%, р = 0.03). The same association of IgG2-Pg with Ki-67 were not revealed. The cooperative individual low IgG2-E2 and IgG2-Pg levels in BCP I stage with Ki-67≤14 tumors were found in 55.2%, but with Ki-67>30 in 22.4%. The cooperative high IgG2-E2 and IgG2-Pg levels were detected in 35.7% BCP I stage with Ki-67≤14 tumors and in 28.6% with Ki-67>30 (p = 0.03). On the contrary, high IgG2-E2 levels in BCP II–IV stages with tumor Ki-67>30 were revealed rarely, than with Ki-67≤14 (49.1% vs 64.2%, р = 0.03). The same association were found with IgG2-Pg (47.2% vs 62.2%, р = 0.03). The cooperative high individual IgG2- E2 and IgG2-Pg levels were detected in BCP II–IV stages with Ki-67≤14 and Ki-67>30 in 38.0% and 37.0 correspondingly. These indicators were 21.5% and 53.9% when the levels of studied antibodies were low (p = 0.003). In conclusion, the cooperative high levels of both IgG2-E2 and IgG2-Pg were associated with high proliferative activity of ER+/PR+ breast cancer in the tumor growth beginning (at the I stage) and with low proliferation of the growing tumors (at II–IV stages).

Keywords

• breast cancer
• antiidiotypic antibodies to progesterone
• antiidiotypic antibodies to estradiol
• ki-67
• progesterone-receptor
• estradiol-receptor