Associations of antibodies to benzo[a]pyrene, estradiol and progesterone with estrogen receptor phenotype in breast cancer tissue

Author:

Polenok E. G.1ORCID,Mun S. A.1ORCID,Gordeeva L. A.1ORCID,Kostyanko M. V.2ORCID,Antonov A. V.3ORCID,Verzhbitskaya N. E.3ORCID,Kolpinskiy G. I.4ORCID,Glushkov A. N.1ORCID

Affiliation:

1. Institute of Human Ecology, Federal Research Center of Coal and Coal Chemistry within the Siberian Branch of the Russian Academy of Sciences

2. Kemerovo State University

3. Kuzbass Clinical Oncological Dispensary

4. Kemerovo State Medical University; Clinical Diagnostic Center

Abstract

Aim. To reveal the associations of IgA antibodies to benzo[a]pyrene, estradiol and progesterone (IgA-Bp, IgA-Es, IgA-Pg) with the conversion of estrogen-receptor positive (ER+) into estrogen-receptor negative (ER-) tumors during breast cancer progression.Materials and Methods. Having collected serum samples from 338 healthy volunteers and 1407 breast cancer patients, we have profiled them for IgA-Bp, IgA-Es, IgA-Pg by means of enzyme-linked immunosorbent assay. Conjugates of bovine serum albumin with Bp, Es and Pg were used as adsorbed antigens and anti-human IgA horseradish peroxidase-conjugated antibodies were used for the detection of specific antigen-bound antibodies. Individual IgA-Bp/IgA-Pg and IgA-Es/IgA-Pg ratios were calculated. Estrogen receptor phenotype was determined using immunohistochemistry.Results. Low IgA-Bp/IgA-Pg ratios (≤ 1) in combination with low IgA-Es/IgA-Pg ratios (≤ 1) indicative of protective immunophenotype were more frequently revealed in healthy women (43.8%) in comparison with stage 1 breast cancer patients with ER+ (12.9%) and ER- (23.9%) tumors. High IgA-Bp/IgA-Pg ratios (>1) with high IgA-Es/IgA-Pg ratios (>1) suggestive of pro-carcinogenic immunological phenotype were less often detected in healthy women (27.5%) as compared with stage 1 breast cancer patients with ER+ (65.5%) and ER- (58.7%) tumors. Prevalence of protective and pro-carcinogenic phenotypes significantly differed in stage 1breast cancer patients with ER+ and ER- tumor phenotypes (p = 0.017). ER- tumor phenotype was more prevalent at II-IV tumor stages (25.6%) than at the stage 1 (16.3%). Conversion of ER+ to ER- tumors reflecting the breast cancer progression was characteristic for the patients with pro-carcinogenic immunological phenotype (p<0.0001).Conclusion. Detection of antibodies against Bp, Es and Pg may be applied as a risk marker of breast cancer development and progression.

Publisher

Kemerovo State Medical University

Subject

General Medicine

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