Expression of ER, PR and Ki-67 in tumor with different genetic variants of ESR and levels of antiidiotypic antibodies to steroid hormones in breast cancer patients

Aim. To study the possible associations of tumor ER, PR and Ki-67 expression with ESR1 and ESR2 genes polymorphisms and blood serum levels of antiidiotypic antibodies IgG2-E2 and IgG2-Pg in breast cancer patients (BCP).

Materials and Methods. Blood serum levels of IgG2-E2 and IgG2-Pg were studied in 1025 BCP (478 with stage I and 547 with stages II-IV) by means of enzyme-linked immunosorbent assay. Real-time PCR was performed for ESR1

(rs2234693) and ESR2 (rs4986938) genes polymorphisms detection. ER, PR and Ki-67 positive tumor cells was determined using immunohistochemistry.

Results. IgG2-E2 and IgG2-Pg blood serum levels were not depended on ESR1 and ESR2 gene polymorphisms in BCP. ER+/PR+ tumors were revealed more frequently and ER-/PR- tumors less frequently in BCP at the I stage with high serum levels of both IgG2-E2 and IgG2-Pg than in BCP with their low levels: in patients with genotype TC ESR1 (91.8 % and 3.3 % vs 73.9 % and 11.1%, p = 0.015). Such differences were not revealed in patients with genotypes TT and CC ESR1. There were not discovered the desired association of ER/ PR tumor phenotype with studied antibodies and ESR2 genes polymorphisms. High levels of tumors Ki-67 positive cells (>20%) were determined less frequently in BCP at the II-IV stages with high levels of both IgG2-E2 and IgG2-Pg than in BCP with their low levels: in patients with genotypes TC ESR1 (48.4 % vs 69.7 %, p = 0.004) and GA ESR2 (46.8 % vs 66.3 %, p = 0.009). There were not revealed such differences in patients with other variants of ESR1 and ESR2 genotypes.

Conclusion. Synergistic effects of IgG2-E2 and IgG2-Pg were discovered in BCP: the maintenance of ER and PR in tumors at the I stage and inhibition of tumor proliferation at the II-IV stages.

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