Immunological heterogeneity of stage I breast cancer:biological, population-based and prognostic value (international cooperation experience)

Aim is to examine the biological, population-based and prognostic value of immunological heterogeneity of stage I breast cancer (BC) in two independent populations (Russian and Dutch).materials and methods: we studied the clinical, morphological characteristics and disease course in 518 patients with stage I BC, who received treatment in N.N.Blokhin Russian Cancer Research Center, in the Hospital of Russian Medical Academy for Postgraduate Education of the Ministry of Health of the Russian Federation (n=315) and in Leiden University Medical Center - LUMC (n=203) between 1985 and 2010 years. Tumor tissue paraffin blocks had been examined at the LUMC; morphological characteristics were included the de-gree of anaplasia, histological type (solid tumor slide) and tumor markers (ER, PR, HER2, Ki67, HC10, HCA2, HLA-E, HLA-G, Foxp3), whose expression was validated by immunohistochemistry on tumor tissue microarrays. The expression of immune markers, the immunological heterogeneity of stage I BC were studied in Russian and Dutch women, and we also indicated 3 types of tumor immunogenicity (high, moderate, low). We studied population and prognostic role of immunogenicity as a further prediction in patients with stage I BC (in the general group, subgroups of patients treating with/without adjuvant systemic therapy). Statistical analysis was performed using international statistical program SPSS 20.0; differences were considered statistically significant when p <0,05.results: tumor immune characteristics in patients with stage I BC have important population-based differences: BC highly express molecules of HLA class I (HC10+ in 91%, HCA2+ in 48%, combined expression of the HC10+ nsa2+ in 48% of cases), and also highly express non-classical markers HLA class I (HLA-E+ in 99%, HLA-G+ in 26%) in russian women. The Russian women breast cancer is highly tumor-infiltrating Foxp3(+) regulatory T-cell (in 73% of cases), associated with the suppression of antitumor response. As a result, Russian women breast cancer is highly immunological only in 14% of the cases. Breast cancer in women in the Netherlands moderately presents the molecules of HLA class I (HC10+ in 74% of cases, HCA2+ in 41%, the combined expression of the HC10+HCA2+ in 38% of cases), moderately expresses non-classical markers (HLA-E+ in 48%, HLA-G+ in 47%) and the tumor-infiltrating Foxp3(+) regulatory T-cell is observed only in 43%; the high immunogenicity of the tumor is indicated in 31% of cases, which can explain the high survival rate in Dutch women suffering from stage I BC without using adjuvant systemic therapy. Immunogenicity of the tumor is the important prognostic factor for both populations; we have noted the higher risk of recurrence, disease progression and death in patients with low tumor immunogenicity in general group and subgroup of women with BC without using adjuvant systemic therapy. The use of adjuvant systemic therapy can help to neutralize the negative impact of low tumor immunogenicity and to significantly improve the prognosis in case of stage I BC.

stage I breast cancer, breast cancer immunobiology, HLA class I histocompatibility genes, tumor-infiltrating Foxp3(+) regula- tory T-cell, immunogenicity of breast cancer