IMMUNOLOGICAL IMBALANCE IN BREAST CANCER AND LUNG CANCER IN POSTMENOPAUSAL WOMEN

Previous studies reported some associations between class A antibodies specific for benzo[a]pyrene (IgA-Bp), estradiol (IgA-Es) and progesterone (IgA-Pg) and breast cancer (BC) in women like as with lung cancer (LC) in men. It was suggested that IgA-Bp and IgA-Es may stimulate tumor initiation and promotion, whereas IgA-Pg may inhibit the in vivo human carcinogenesis.The purpose of this study was to identify the suggested associations of such immunological imbalance with BC and LC in postmenopausal women.The serum A-class antibodies specific to benzo[a]pyrene, estradiol and progesterone (IgA-Bp, IgA-Es, IgA- Pg) were studied in 335 healthy women, 824 breast cancer (BC) patients and 127 cases of lung cancer (LC) by means of non-competitive solid phase immunoassay. The following results were obtained: Increased ratio of IgA-Bp and IgA-Es amounts exceeding the IgA-Pg levels was associated with a higher risk of breast cancer (OR = 2.8 and 2.4 respectively, p < 0.0001), and higher risk of LC (OR = 2.9 and 2.8, respectively, p < 0.0001). Conversely, the OR values decreased to 0.3-0.4 for BC and LC if IgA-Pg levels were higher than IgA-Bp and IgA-Es levels (p < 0.0001). These findings confirm the hypothesis that IgA-Bp and IgA-Es are capable to stimulate, and IgA-Pg, to inhibit the BC and LC occurrence n postmenopausal women. The balance between IgA-Bp and IgA-Es, on the one hand, and IgA-Pg, on the other hand, is much more important than individual contents of these antibodies.In conclusion, the phenomenon of “immunological interference” is revealed, i.e., the mutual enhancement of IgA-Bp and IgA-Es effects, thus, probably, stimulating the initial and subsequent events of carcinogenesis initiation and promotion, with a weak anticancer effect of IgA-Pg, and by weakening the mutual procarcinogenic effects of IgA-Bp and IgA-Es by the marked effect of IgA-Pg

IMMUNOREGULATION OF BLOOD SERUM ESTRADIOL AND PROGESTERONE LEVELS IN POSTMENOPAUSAL WOMEN

Specific antibodies against estradiol (Es) and progesterone (Pg) are known to modulate blood serum concentrations of these hormones and their biological effects after immunization of animals. It was suggested that specific IgA-Es and IgA-Pg could influence on Es and Pg levels in human blood serum. The purpose of this study was to identify the suggested correlations between serum Es and Pg and specific IgA-Es and IgA-Pg in postmenopausal healthy women (HW) and breast cancer patients (BCP). The serum levels of Es, Pg, IgA-Es and IgA-Pg were studied in 226 HW and 633 BCP by means of solid-phase immunoassay. The following results were obtained. The levels of Es in BCP (0.25 nmol/l) were higher than in HW (0.16; р < 0.0001). The levels of Pg were lower (0.79 vs 0.87; р < 0.0001), and individual Pg/Es ratios were lower (3.19 vs 6.64; р < 0.0001). Individual IgA-Pg/IgA-Es ratios correlated with decrease of Es (rs = -0.15; p = 0.029), with increase in Pg (rs = 0.38; р < 0.0001), and with increased Pg/Es ratio (rs = 0.29; р < 0.0001) in healthy women. Similar correlations were determined in BCP (correspondingly: rs = -0.14, р < 0.001; rs = 0.1, р = 0.009; rs = 0.15, р < 0.0001). The decrease of Es and increase of Pg and Pg/Es in BCP were less significant than in HW: the a quotients in regression у = ах+b (y = hormones levels and x = antibodies levels) in BCP were 3 to 4-fold lower than in HW. These peciliarities of interrelations between hormones and specific antibody levels were revealed only in ER+/PR+ BCP but not in ER+/PR- and ER-/PR- BCP. In conclusion, we have confirmed a suggestion about participation of specific antibodies in regulation of steroids levels in human blood serum. The immune regulation of hormonal status was weakened in BCP

Immunological imbalance, gene polymorphism of biotransformation enzymes, and steroid hormone receptors in tumors in breast cancer patients

It is well known that results of breast cancer (BC) hormonal therapy depend on expression of tumor estradiol and progesterone receptors (ER and PR) in tumor tissue. Mechanisms of ER+/PR+ tumors conversion to ER+/PR- and ER-/PR- tumors remain scarcely studied. The decrease of steroid receptors expression seems to depend on action of genotoxic metabolites of environmental carcinogens (particularly, benzo[a]pyrene, BP) and endogenous steroids (in particular, estradiol, E2). The formation of these metabolites is regulated by the biotransformation enzymes. On the other hand, the formation of DNA-adducts with genotoxic metabolites may induce the synthesis of specific antibodies. Previously, it was shown that increase of the serum IgA-antibodies levels against Bp and E2 over the levels of IgA-antibodies against progesterone (IgA-Bp/IgA-Pg > 1 and IgA-E2/IgA-Pg), could be interpreted as immunological imbalance associated with high BC risk in healthy women. The purpose of this study was to detect the suggested associations between ER+/PR+ tumors conversion to ER+/PR+ and ER-/PR- tumors and immunological imbalance in the BC patients with distinct gene variants of biotransformation enzymes: CYP1A1*2A (rs 4646903), CYP1B1 (rs1056836), CYP19A1 (rs2470152), GSTT1 (del), GSTP1 (rs1695). The IgA-Bp, IgA-E2 and IgA-Pg were studied in 1321 non-smoking BC patients by non-competitive solid phase immunoassay. The conjugates of Bp, E2 and Pg with bovine serum albumin were adsorbed as target antibodies. The goat antibodies against human IgA conjugated with horseradish peroxidase were used for detection of the studied specific antibodies. Gene polymorphisms of biotransformation enzymes were analyzed by the real-time PCR. Tumor ER and PR were detected by the standard immunohistochemical methods.ER+/PR+ tumors in BC patients at the stage I (N = 534) were found in 68.7%, ER+/PR- in 15.6%, ER-/ PR- in 15.7%. In BC patients at the II-IV stage (N = 787), frequency of ER+/PR+ tumors decreased to 60.2%, ER+/PR- was similar (15.8%), and ER-/PR- increased to 24.0% (p < 0.0001). These alterations were revealed in BC patients at the IgA-Bp/IgA-Pg ratios > 1, and IgA-E2/IgA-Pg > 1 only. There were no differences found between BC patients at stage I and II-IV at the ER+/PR+, ER+/PR-, ER-/PR- frequencies when these ratios were low.The frequency of ER+/PR+ tumors in homozygotes TT of CYP19A1 was 77.1% at the I stage and 60.1% at the II-IV stages. Respectively the frequencies of ER-/PR- tumors were 11.8% and 26.1% (p < 0.001). ER+/ PR+ tumors were revealed in GSTT1 “+” BC patients at the I stage in 68.7% and at the II-IV stages in 58.0%. Respectively ER-/PR- tumors were found in 16.6% and 24.5% (p < 0.0004). The frequency of ER+/PR+ tumors was 57.1% in homozygotes GG of GSTP1 at the I stage and 60.7% at the II-IV stages. Respectively the frequencies of ER+/PR- were 14.3% and 22.2% and ER-/PR- were 28.6% and 19.0% (p < 0.001). Proportions of low and high IgA-Bp/IgA-Pg and IgA-E2/IgA-Pg ratios were the same at the any enzyme genotype of studied CYP or GST variants. In conclusion, we have revealed a sufficient contribution of immunological imbalance to the conversion of steroid receptors in breast cancer growth, being independent of several CYP and GST gene polymorphisms

ANTIBODIES AND ANTI-ANTIBODIES TO STEROID HORMONES, AND BREAST CANCER RISK

Antibodies against sex steroid hormones are known to modulate their serum concentration and  inhibit experimental breast cancer (BC). Hence, these effects could be changed by according anti-idiotypic  antibodies. However, relationships between antibodies and anti-idiotypic antibodies and BC in women are still  poorly studied. The aim of this study was to identify possible associations between occurrence of antibodies  against estradiol and progesterone (IgG-Es1and IgG-Pg1) and according antiidiotypic antibodies (IgG-Es2  and IgG-Pg2), and postmenopausal BC.  Eighty-nine  healthy  women  and  273  BC  patients  were  examined.  A  non-competitive  solid  phase  immunoassay for IgG-Es1 and IgG-Pg1 was performed using estradiol and progesterone conjugates with bovin  serum albumin as antigens. Monoclonal antibodies against Es and Pg as antigens have been used for noncompetitive solid phase immunoassay of IgG-Es2 and IgG-Pg2.  Results: absence of both IgG-Es1 and IgG-Pg1 was revealed in 53.9% of healthy donors and 41.0% of  BC patients (p = 0.04; OR = 0.6). Presence of IgG-Es1 without IgG-Pg1, or IgG-Pg1 without IgG-Es1was  detected for, respectively, 15.7% and 20.2% of healthy women, and in 10.3% and 7.7% of BC patients (p > 0.05).  Simultaneous increase of both IgG-Es1 and IgG-Pg1 was revealed in 10.1% of healthy donors and in 41.0%  of BC patients (p < 0.0001; OR = 5.3). Absence of a single antibogy (IgG-Es2 or IgG-Pg2) showed similar  frequency in the groups under study. Simultaneous increase of both IgG-Es2 and IgG-Pg2 was detected in  52.8% of healthy women and 34.8% of BC patients (p = 0.03; OR = 0.4). Conclusion: We have first revealed  an immunostimulating synergistic effect of antibodies against sex steroid hormones and immunoinhibitory  synergistic effect of appropriate anti-idiotypic antibodies upon the postmenopausal breast cancer risk

Immunophenotypic investigation of infant acute lymphoblastic leukemia

Aim of the study – immunophenotype description of infant acute lymphoblastic leukemia (ALL). 64 patients (29 boys and 35 girls) with acute leukemia (AL) aged from 0 to 11 months were included in the current study. ALL was found less frequently in infants than in older children (67.19 % and 87.69 %, respectively). BI-ALL was the most common immunological ALL type (60.46 %) in infant ALL, while BII-ALL was notably less frequent compared with other age groups (30.23 %). Significant immunophenotypic differences were observed in patients with and without MLL gene rearrangements. Number of cases in those tumor cells expressed CD10, CD20, CD45, CD133, CD15, NG2 varied between MLL-positive and MLL-negative groups. CD10- and CD20-negativity, high CD45, CD15, CD65 and NG2 expression were immunophenotypic signatures of MLL-rearranged infant ALL, although NG2 had the highest diagnostic efficacy. High CD34 and CD65 expression was frequently associated with presence of MLL-AF4 fusion gene. Thus infants’ B-cell precursor ALL immunophenotype differs significantly due to the presence of MLL gene rearrangements. Diagnostic immunophenotyping of infants’ ALL allows predicting presence of MLL rearrangements and NG2 is the most applicable single marker.</p

Immunophenotypic investigation of infant acute myeloid leukemia

Aim of the study – characterization of immunophenotype in infant acute myeloid leukemia (AML). 90 patients (40 boys and 50 girls) with acute leukemia (AL) aged up to 365 days were included in the current study. AML was found more frequently in infants than in older children (26.67 % and 10.83 % respectively; p = 0.0002). Significant immunophenotypic differences were observed in patients with and without MLL gene rearrangements. Number of cases in those tumor cells expressed CD99, CD61, CD133, CD15, NG2 varied between MLL-positive and MLL-negative groups. CD61-negativity, high CD99, CD15, CD133 and NG2 expression were immunophenotypic signatures of MLLrearranged infant AML, although CD99 and NG2 had the highest diagnostic efficacy. Thus infants’ AML immunophenotype differs significantly due to the presence of MLL gene rearrangements. Diagnostic immunophenotyping of infants’ AML allows predicting presence of MLL rearrangements by either CD99 or NG2 expression.</p

Immunoassayofantibodies to benzo[a]pyrene, estradiol and progesterone fordeterminationofpersonal lung cancer riskinmen

A personalized lung cancer risk assessment is important for disease prevention.The aim of the studywas to estimate a significance of immunoanalysis of antibodies to benzo[a]pyrene, estradiol and progesterone for lung cancer risk prediction in men with respect to age and smoking.Material and methods. Serum antibodies to benzo[a]pyrene, estradiol and progesterone in the blood serum of 620 healthy men (279 smokers) and 827 lung cancer patients (627 smokers) were studied using semi-quantitative enzyme immunoassay.Results. The high lung cancer risk was observed in smokers aged over 55 years: oR=15.4 (11.5–20.8 95 % ci). the lung cancer risk in this group of patients was significantly lower when their levels of antibodies to benzo[a]pyrene and to estradiol were lower than those to progesterone: oR=3.2 (2.0–5.0). the lung cancer risk was higher when the personal levels of antibodies to benzo[a]pyrene and to estradiol were higher than the levels of antibodies to progesterone: oR=20.0 (10.5–38.1).Conclusion. The immunoassay of the blood serum antibodies specific to benzo[a]pyrene, estradiol and progesterone could be useful for determination of the lung cancer risk in men

Immunophenotypic features of bone marrow tumor cell in Burkitt lymphoma/leukemia: B-lineage acute lymphoblastic leukemia diagnostics opportunities

Bone marrow tumor blasts immunophenotyping is an essential part of Burkitt lymphoma/leukemia (BL) and B-cell precursor acute lymphoblastic leukemia (BCP-ALL) differential diagnostics. Nevertheless immunoglobulin heavy and light chains detection on the cell surface could meet several biological and methodological pitfals. Thus the aim of the present study was development of additional BL immunophenotypic criteria. Leukemic blasts antigen profile in 21 BL cases and 84 children with BCP-ALL was compared in a retrospective way. Antigen expression patterns in BL and BCP-ALL were significantly different. It was shown that even in cases with weak immunoglobulin M expression these two tumor types could be distinguished well by complex immunophenotype analysis. In present study all cases of CD34-negative B-lineage ALL without myeloid coexpression and with high CD20-positive cells proportion belonged to BL