Derivatized versus non-derivatized LC-MS/MS techniques for the analysis of estrogens and estrogen-like endocrine disruptors in human plasma.

Bisphenols, parabens, alkylphenols and triclosan are anthropogenic substances with a phenolic group that have been introduced to the environment in recent decades. As they possess hormone-like effects, they have been termed endocrine disruptors (EDs), and can interfere with steroid pathways in organisms. To evaluate the potential impact of EDs on steroid biosynthesis and metabolism, sensitive and robust methods enabling the concurrent measurement of EDs and steroids in plasma are needed. Of crucial importance is the analysis of unconjugated EDs, which possess biological activity. The aim of the study was to develop and validate LC-MS/MS methods with and without a derivatization step for the analysis of unconjugated steroids (estrone-E1, estradiol-E2, estriol-E3, aldosterone-ALDO) and different groups of EDs (bisphenols, parabens, nonylphenol-NP and triclosan-TCS), and compare these methods on a set of 24 human plasma samples using Passing-Bablok regression analysis. Both methods were validated according to FDA and EMA guidelines. The method with dansyl chloride derivatization allowed 17 compounds to be measured: estrogens (E1, E2, E3), bisphenols (bisphenol A-BPA, BPS, BPF, BPAF, BPAP, BPZ, BPP), parabens (methylparaben-MP, ethylparaben-EP, propylparaben-PP, butylparaben-BP, benzylparaben-BenzylP), TCS and NP, with lower limits of quantification (LLOQs) between 4 and 125 pg/mL. The method without derivatization enabled 15 compounds to be analyzed: estrogens (E1, E2, E3), ALDO, bisphenols (BPA, BPS, BPF, BPAF, BPAP, BPZ), parabens (MP, EP, PP, BP, BenzylP) with LLOQs between 2 and 63 pg/mL, and NP and BPP in semiquantitative mode. Adding 6 mM ammonium fluoride post column into mobile phases in the method without derivatization achieved similar or even better LLOQs than the method with the derivatization step. The uniqueness of the methods lies in the simultaneous determination of different classes of unconjugated (bioactive) fraction of EDs together with selected steroids (estrogens + ALDO in the method without derivatization), which provides a useful tool for evaluating the relationships between EDs and steroid metabolism.

THE NASOLABIAL FLAP: THE MOST VERSATILE METHOD IN FACIAL RECONSTRUCTION.

The nasolabial flap was described 170 years ago and still remains one of the most frequently used methods in facial reconstruction. This technically easy and maximally effective procedure has become a real workhorse and an integral instrument for every plastic surgeon. Over time multiple modifications of this technique have been described. In this article, authors present an overview of nasolabial flap modalities and discuss advantages and disadvantages of these techniques.

POSTOPERATIVE FIXATION AFTER REPOSITIONING OF PREMAXILLA IN A PATIENT WITH BILATERAL CLEFT LIP AND PALATE - CASE REPORT.

This article presents orthodontic-surgical treatment in an eight-year-old patient with bilateral cleft lip and palate where premaxilla was surgically repositioned in the mixed dentition stage. By cranial and dorsal insertion of the premaxilla were created satisfactory occlusal relationship for ongoing eruption of permanent teeth, together with functional lip closure, improved pronunciation and a positive change in appearance of the centrofacial area. Reposition of premaxilla was associated with bilateral alveolar bone grafting of the cleft defect with cancellous bone from the iliac crest. Based on the model surgery were prepared rigid orthodontic wires, which ensured postoperative fixation of the segments of the upper jaw. The patient was wearing band fixed appliance for another 6 months after surgery. Healing was uncomplicated, the new position of the premaxilla was stable and more physiological. This procedure was friendly for a child patient and did not require fixation of the jaw segments by Sauer splint.

The Relationship of Kynurenine and Neopterin Levels and Their Association with a Selection of Other Immune Markers in Chronic Myeloid Leukaemia Patients.

Among malignant diseases, chronic myeloid leukaemia (CML) is one of the best suited candidates for immunotherapy. For this purpose it is necessary to broaden the present knowledge on the immunology of this disease. As a part of such a project, the levels of kynurenine (KYN) and neopterin (NPT) were studied in 28 CML patients and in the same number of healthy subjects. At diagnosis, both KYN and NPT levels were found to be elevated in a significant portion of the patients and dependent on their leukocyte count. As in the case of KYN, increased NPT levels dropped after achieving remission. When correlating KYN and NPT levels with a selection of other markers tested, significant association was revealed only in the case of CRP and IL-6. However, there were several patients with increased KYN levels in whom NPT was not detected, and vice versa. The relapse of the disease observed in two patients was accompanied by an increased level of NPT in both cases, but by an increased level of KYN in only one of them. No significant correlation was found between KYN and NPT levels in sera taken at diagnosis. However, when the whole set of sera was taken into consideration, the association became statistically significant. Although the data obtained revealed a number of similarities between KYN and NPT production in CML patients, it also suggested a difference in the kinetics of these two biomarkers' production.

OVARIAN GOITER AS A RARE CAUSE OF HYPERTHYROIDISM.

INTRODUCTION: Thyroid tissue ectopically located in the ovary can be reported accidentally after adnexectomy, but as a primary cause of hyperthyroidism this diagnosis is rare. The clinical search for a functional ectopic thyroid tissue requires intense clinical focus and a multidisciplinary approach. CASE DESCRIPTION: This case report demonstrates a patient with a history of Graves' disease who had undergone thyroidectomy combined with postoperative 131I radioablation. Despite the previous treatment, she developed an outburst of hyperthyroidism ten years later. Only very close follow-up enabled us to disclose the right condition. The ovarian source of thyroid hormone production was removed by laparoscopic adnexectomy and a right sided benign ovarian struma was confirmed. CONCLUSION: Most patients treated by thyroidectomy and radioiodine do not require extended periods of follow-up or postoperative investigations, but when the clinical or laboratory signs change, clinicians should be prepared to perform the necessary re-evaluation in order to provide the best care.

[Smoking in pregnancy - negative impacton mother and child Opinions on nicotine substitution]. / Kourení v tehotenství - dusledky pro matku a díte Soucasné názory na nikotinovou substituci.

Cigarette smoking (tobacco abuse) is legal in the Czech Republic and use of this drug is more or less tolerated there. Argumentation about economic benefits of the production and sale of tobacco products in this country is not responsibly given in context with the level of damage to health. The state does not consistently take into action restrictive measures to prevent this negative phenomenon. Even the medical community adopts an indifferent attitude. Although there have been found countless hard evidence about the harmful effects of smoking on the mother and fetus/baby. Even very small amounts of cigarettes has a negative impact on mother, placental perfusion and ultimately the child. The aim of the article is to describe the pathophysiology of tobacco abuse on mother and baby and to simultaneously open a space for discussion about the treatment of smokers during their pregnancy.

The effect of helper epitopes and cellular localization of an antigen on the outcome of gene gun DNA immunization.

In DNA vaccination, CD4(+) T-cell help can be enhanced by fusion of a gene encoding an immunization protein with a foreign gene or its part providing T(h) epitopes. To study the effect of helper epitope localization in a protein molecule, the influence of the vicinity of the helper epitope, and the impact of chimeric protein cellular localization, we fused the helper epitope p30 from tetanus toxin (TT, aa 947-967) with the N- or C-terminus of the mutated E7 oncoprotein (E7GGG) of human papillomavirus type 16, enlarged the p30 epitope with the flanking residues containing potential protease-sensitive sites and altered the cellular localization of the fusion constructs by signal sequences. The p30 epitope enhanced the E7-specific response, but only in constructs without added signal sequences. After localization of the fusion proteins into the endoplasmic reticulum and endo/lysosomal compartment, the TT-specific T(h)2 response was increased. The synthetic Pan DR epitope (PADRE) induced a stronger E7-specific response than the p30 epitope and its stimulatory effect was not limited to nuclear/cytoplasmic localization of the E7 antigen. These results suggest that in the optimization of immune responses by adding helper epitopes to DNA vaccines delivered by the gene gun, the cellular localization of the antigen needs to be taken into account.

[Intrahepatic cholestasis of pregnancy]. / Intrahepatální cholestáza v tehotenství

The review of intrahepatic cholestasis of pregnancy attempts to summarize the current knowledge of this disease by analysing available literary sources. Intrahepatic cholestasis of pregnancy is a disease that typically appears in the third trimester of pregnancy, sometimes already at the end of the second trimester of pregnancy. The main symptom of the disease is pruritus. In addition, the disease is characterized by increased levels of liver enzymes and bile acids. The symptoms of the disease disappear spontaneously after delivery. The disease is associated with high incidence of fetal distress, as well as with a high risk of premature labour. The most serious obstetric complication is antenatal sudden fetal death. Fetal complications are probably caused by elevated levels of bile acids. Therefore the aim of treatment should be to minimize negative effects of bile acids on the fetus, to prolong pregnancy and reduce maternal symptoms at the same time.

The interpolation nasolabial flap: the advantageous solution for nasal tip reconstruction in elderly and polymorbid patients.

BACKGROUND: Nasal tip is one of the most frequent areas affected by basocellular carcinoma. The treatment must avoid any postsurgical deformity, as the nasal tip is the main part of the facial triangle. Most of these patients are elderly and polymorbid. The surgeon must find a compromise between the cosmetic effect and an acceptable stress for the patient. METHODS: There were five methods of nasal tip reconstruction used on a group of fifty elderly patients with various medical comorbidities: skin graft, bilobed flap, dorsal nasal flap, forehead flap and interpolation nasolabial flap. The resulting cosmetic effect was objectivized by a standardized questionnaire and the advantages and disadvantages of each method were discussed. RESULTS: According to the characteristics that were considered (good vascular supply, matching skin color and texture, sufficient amount of material, possibility to cover exposed cartilage or to combine it with cartilaginous graft; scars of minimal visibility, perfect aesthetic outcome, use of local anesthesia, short surgical time, and technical simplicity) was the interpolation nasolabial flap found as the most appropriate. CONCLUSION: Interpolation nasolabial flap is an easy and effective method for treatment of smaller and middle-sized defects of the nasal tip with minimal stress for the patient. LEVEL OF EVIDENCE: Level III.

The role of taste in cephalic phase of insulin secretion.

The effect of a short gustatory signal of a sweet solution was tested on 15 young male volunteers. The experiment consisted of mouth rinsing with either a sucrose or aspartate solution or pure water as a placebo. Blood was then taken in short intervals of 0, 5, 10, 15 and 20 min. Blood glucose, C-peptide, insulin and cortisol were determined. While C-peptide and glucose were unaffected, a short-term increase in insulin was observed after the sucrose, but not after the aspartate or placebo. The increase in insulin was significant, though it amounted to only 0.5 mIU/l and lasted approx. 15 min reaching then the starting value. The decline of cortisol level within 20 min of the experiment was approx. 40 nmol/l, although it was also observed after aspartate or placebo mouth rinsing and was probably caused by stress factors or anticipation. In conclusion, the contribution of taste to the cephalic phase of insulin secretion is small yet significant, and mouth rinsing with 5% sucrose causes an insulin increase of just under 1 IU/l, which returns to starting level within 15 min.

The Effects of Different Types of Diets on Steroid Hormone Concentrations.

The great popularity of various diets in recent years has led us to reflect on their suitability for our health. The aim of this communication is to review current knowledge on the influence of the most well-known diets on the concentrations of the main steroids and to consider possible mechanisms. The influence of diet on hormone concentrations is expected, but the literature data on this topic are inconsistent and yield conflicting results. The main problem in evaluating these influences is the change in weight that a change in diet induces. This effect needs to be filtered out in order to discover interesting associations between diet and steroid hormones. This is illustrated by the example of the effects of ketogenic diets on testosterone levels in men, where the direct effect of the diet is to reduce testosterone levels, but a number of papers have described increases that are due to diet-related weight loss and the modification of obesity-induced changes. A second major driver is the change in circadian rhythm, and it is necessary to assess hormonal changes induced by changing the time of day of the diet. Such shifts within the circadian rhythm rather than due to a particular type of diet itself are documented by changes in the circadian rhythm of cortisol.

The Endocannabinoid System and Its Relationship to Human Reproduction.

The endocannabinoid system is among the most important regulators of human reproduction. It already applies at the level of the sperm and the egg, plays an important role in the fertilization of the egg, its implantation, regulates the function of the placenta and participates in childbirth. The aim of this work is to summarize the knowledge accumulated so far and to show that the endocannabinoid system must be perfectly regulated in order to maintain a physiological pregnancy from implantation to delivery. Only an exceptional interplay of enzymes such as NAPE-PDL or FAAH, endogenous cannabinoids and cannabinoid receptors CB1 and CB2 can ensure the proper functioning of the reproductive organs and thus lead to delivery on time. Changes in the endocannabinoid system can lead to a number of pathological conditions, e.g., during blastocyst implantation, retardation of embryo development, impaired placental function or miscarriage. Soon, we can expect not only an understanding of all the regulatory events associated with the endocannabinoid system and other regulatory systems that participate in reproduction, but also several possibilities for pharmacotherapeutic interventions that can modify the formation, degradation and effect of endocannabinoids. It cannot be ruled out that some components of the endocannabinoid system could become a marker for monitoring pregnancy and childbirth.

The Endocannabinoid System - The Prediction of Spontaneous Preterm Birth in High-Risk Women: Protocol of a Study.

Spontaneous preterm birth (sPTB) is a major cause of perinatal morbidity and mortality, even in developed countries. Prediction of sPTB is therefore a valuable tool to reduce the associated risks. The current standard for the prediction of sPTB consists, in addition to anamnestic data, of previous sPTB and previous second trimester miscarriage, measurement of cervical length by transvaginal ultrasound (TVU CL) together with assessment of fetal fibronectin levels in cervicovaginal fluid. Other evaluation parameters, such as the level of endocannabinoids in the pregnant woman's blood, could increase the sensitivity of this management. Endocannabinoids (eCBs) are a part of the endocannabinoid system (ECS); out of them anandamide (arachidonoyl-ethanolamide, AEA), in particular, plays an important role in the regulation of pregnancy and childbirth. We present the protocol for an open, non-randomized study to evaluate concentrations of AEA and other endocannabinoids: 2 linoleoylglycerol (2-AG), 2 linoleoylglycerol (2-LG), 2 oleoylglycerol (2-OG), and 2 arachidonoyldopamine (2-ADOPA or also NADA) in the blood of pregnant women as potential predictors of sPTB. In a total of 230 women with a history of sPTB or miscarriage, eCBs levels between 22 and 28 weeks of gestation will be assessed from maternal blood, in addition to the standard procedure. The aim of the study is to determine the relationship between blood concentrations of the endocannabinoids tested and the risk of sPTB. The results of this study will describe the prognostic significance of maternal blood eCBs levels for sPTB, and could subsequently enable improved screening programs for early identification of sPTB.

Androgens in SARS-CoV-2 coronavirus infections.

Recent molecular biology findings have shown that for the penetration of the SARS-CoV-2 coronavirus into host cells, a key role is played by protease serine 2, the activity of which is dependent on androgens. The important role of androgens is also evidenced by clinical observations that men in some age categories are infected by this novel coronavirus up to two times more frequently than women. In addition, men with androgenic alopecia tend to have more serious clinical courses, while men with androgen deprivation as a result of prostate cancer treatments tend to have milder courses. This is in line with the fact that preadolescent children are only rarely sickened with serious forms of SARS-CoV-2 infections. Even though these observations may be explained by other factors, many authors have hypothesized that lowered androgen levels and blocking their activity using anti-androgen medication may moderate the course of the viral infection in intermediately- to critically-affected cases. Clearly, it would be important for androgen deprivation to block not just gonadal androgens, but also adrenal androgens. On the other hand, low androgen levels are considered to be a risk factor for the course of SARS-CoV-2 infections, either because low androgen levels have a general effect on anabolic-catabolic equilibrium and energy metabolism, or because of the ability of testosterone to modify the immune system. It is not yet clear if infection with this novel coronavirus might induce hypogonadism, leading to undesirable side effects on male fertility.

In vitro and in vivo effects of reovirus on HPV16-transformed mice cells.

UNLABELLED: Oncolytic viruses are examined to serve as anticancer therapeutics. It is expected that in addition to direct oncolytic effect their action will also help eliciting a solid antitumor immunity. In presented series of experiments we have employed two HPV16-transformed mouse (strain C57/B6) cell lines, TC-1 and MK16/III/ABC (MK16), and reovirus type 3, strain Dearing (RV). Both cell lines are highly susceptible to RV and produce large amounts of infectious virus in vitro while normal human are not susceptible to RV. Still, some differences were encountered. TC-1 cells produced moderately lesser amounts of infectious virus, but, paradoxically, were more efficient producers of delta1 antigen of RV and as a consequence of virus infection died more rapidly than simultaneously infected MK16 cells. Minor differences between the cell lines were observed in the percentage of cells arrested in theG2/M phase of the cell cycle and in some markers of apoptosis. When inoculating high doses (5x106) of infected cells (MOI 10 PFU/cell) into syngeneic animals their oncogenic activity was strongly suppressed, nearly completely in the case of MK16 cells and somewhat less efficiently in the case of more oncogenic TC-1 cells. Immunizing experiments in which non-oncogenic doses (106) of RV infected TC-1 cells were tested in parallel with the same doses of irradiated cells brought surprising results. When immunized animals were challenged with TC-1 cells, the irradiated cells proved to be a much better immunogen that the infected cells. However, when challenged with MK16 cells the opposite was true. It is believed that this difference was associated with the different biological properties of the cell lines tested. KEYWORDS: reovirus type 3, HPV16-transformed mouse cell lines, apoptosis, cell cycle, immunization/challenge experiments.

Higher levels of salivary alpha-amylase predict failure of cessation efforts in male smokers.

The ability to predict the success or failure of smoking cessation efforts will be useful for clinical practice. Stress response is regulated by two primary neuroendocrine systems. Salivary cortisol has been used as a marker for the hypothalamus-pituitary-adrenocortical axis and salivary alpha-amylase as a marker for the sympathetic adrenomedullary system. We studied 62 chronic smokers (34 women and 28 men with an average age of 45.2+/-12.9 years). The levels of salivary cortisol and salivary alpha-amylase were measured during the period of active smoking, and 6 weeks and 24 weeks after quitting. We analyzed the men separately from the women. The men who were unsuccessful in cessation showed significantly higher levels of salivary alpha-amylase over the entire course of the cessation attempt. Before stopping smoking, salivary cortisol levels were higher among the men who were unsuccessful in smoking cessation. After quitting, there were no differences between this group and the men who were successful in cessation. In women we found no differences between groups of successful and unsuccessful ex-smokers during cessation. In conclusions, increased levels of salivary alpha-amylase before and during smoking cessation may predict failure to quit in men. On the other hand, no advantage was found in predicting the failure to quit in women. The results of our study support previously described gender differences in smoking cessation.

Is maternal progesterone actually independent of the fetal steroids?

Progesterone and estradiol are the foremost steroid hormones in human pregnancy. However, the origin of maternal progesterone has still not been satisfactorily explained, despite the generally accepted opinion that maternal LDL-cholesterol is a single substrate for placental synthesis of maternal progesterone. The question remains why the levels of progesterone are substantially higher in fetal as opposed to maternal blood. Hence, the role of the fetal zone of fetal adrenal (FZFA) in the synthesis of progesterone precursors was addressed. The FZFA may be directly regulated by placental CRH inducing an excessive production of sulfated 3beta-hydroxy-5-ene steroids such as sulfates of dehydroepiandrosterone (DHEAS) and pregnenolone (PregS). Due to their excellent solubility in plasma these conjugates are easily transported in excessive amounts to the placenta for further conversion to the sex hormones. While the significance of C19 3beta-hydroxy-5-ene steroid sulfates originating in FZFA for placental estrogen formation is mostly recognized, the question "Which maternal and/or fetal functions may be served by excessive production of PregS in the FZFA?" - still remains open. Our hypothesis is that, besides the necessity to synthesize de novo all the maternal progesterone from cholesterol, it may be more convenient to utilize the fetal PregS. The activities of sulfatase and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) are substantially higher than the activity of cytochrome P450scc, which is rate-limiting for the placental progesterone synthesis from LDL-cholesterol. However, as in the case of progesterone synthesis from maternal LDL-cholesterol, the relative independence of progesterone levels on FZFA activity may be a consequence of substrate saturation of enzymes converting PregS to progesterone. Some of the literature along with our current data (showing no correlation between fetal and maternal progesterone but significant partial correlations between fetal and maternal 20alpha-dihydroprogesterone (Prog20alpha) and between Prog20alpha and progesterone within the maternal blood) indicate that the localization of individual types of 17beta-hydroxysteroid dehydrogenase is responsible for a higher proportion of estrone and progesterone in the fetus, but also a higher proportion of estradiol and Prog20alpha in maternal blood. Type 2 17beta-hydroxysteroid dehydrogenase (17HSD2), which oxidizes estradiol to estrone and Prog20alpha to progesterone, is highly expressed in placental endothelial cells lining the fetal compartment. Alternatively, syncytium, which is directly in contact with maternal blood, produces high amounts of estradiol and Prog20alpha due to the effects of type 1, 5 and 7 17?-hydroxysteroid dehydrogenases (17HSD1, 17HSD5, and 17HSD7, respectively). The proposed mechanisms may serve the following functions: 1) providing substances which may influence the placental production of progesterone and synthesis of neuroprotective steroids in the fetus; and 2) creating hormonal milieu enabling control of the onset of labor.

Immunohistochemical evaluation and lymph node metastasis in surgically staged endometrial carcinoma.

OBJECTIVE: To assess the expression of immunohistochemical markers in surgically staged endometrial cancer patients. METHODS: We studied 107 cases of primary untreated endometrial carcinoma in which the p53, bcl-2, her-2/neu, Ki-67, estrogen receptor (ER) and progesterone receptor (PR) antigens were investigated by an immunohistochemical method. In the last 50 consecutive patients immunoreactivity for MMP-7 and MMP-26 was assessed as well. We evaluated the correlations among the immunohistochemical staining assessed by histoscore, and the age, grading, depth of invasion, stage of the neoplasia and extrauterine disease. RESULTS: Mean age was 65 years (range 34-88). All patients were submitted to total abdominal or modified radical vaginal hysterectomy plus bilateral salpingo-oophorectomy and systematic pelvic lymphadenectomy; p53, bcl-2, her-2/neu, Ki-67, MMP-7, MMP-26, estrogen and progesterone receptors were positive in 36 (43%), 71 (86%), 13 (16%), 80 (96%), 65 (78%), 80 (96%), 61 (73%) and 71 (86%) patients, respectively. p53 overexpression was found to be related to poor grade of differentiation and deep myometrial invasion. Immunostaining for ER was inversely related to the histopathological differentiation of the tumors. Decreased expression of PR was related to advanced stage, poor histopathologic differentiation and extrauterine spread of disease. CONCLUSION: The overexpression of p53 seems to indicate more malignant phenotype, while PR expression correlates with parameters of better clinical outcome.

[Prognostic significance of clinic pathological and selected immunohistochemical factors in endometrial cancer]. / Prognostický význam klinickopatologických a vybraných imunohistochemických faktoru u karcinomu endometria.

OBJECTIVE: To assess the immunohistochemical expression of p53, bcl-2, c-erbB-2, Ki-67, estrogen (ER) and progesterone (PR) receptors in endometrial cancer patients. To assess the relation between steroid receptors positivity and other markers. To evaluate the prognostic significance of clinicopathologic and immunohistochemical markers on patient disease free survival. DESIGN: Experimental prospective study. SETTING: Department of Obstetrics and Gynaecology, Institute of Human Genetics, Department of Pathology, Department of Biophysics, Palacky University Medical School and University Hospital, Olomouc. METHODS: We studied 144 cases of primary untreated endometrial carcinoma in which the p53, bcl-2, c-erbB-2, Ki-67, ER and PR antigens were investigated with the use of an immunohistochemical method. In a group of 122 patients we assessed disease free survival (DFS) in relation to clinicopathologic and immunohistochemical factors. RESULTS: From the total group of 144 patients, 122 were included for survival analysis. We found 15 (12.3%) patients with recurrence of the disease. Mean age was 64,5 (34-88) years. Immunohistologic expression was p53 positive in 29 (23.8%), bcl-2 positive in 87 (71.3%), c-erbB-2 positive in 34 (27.9%), Ki-67 positive in 56 (45.9%), ER positive in 97 (79.5%) and PR positive in 106 (86.9%) of cases. In the survival analysis significantly shorter DFS was present in tumours with poor differentiation (G3), deep myometrial invasion (M2) and positive lymphoinvasion (N). CONCLUSION: Only poor differentiation (G3) and deep myometrial invasion (M2) are significant independent factors for the length of DFS.

[Immunohistochemical markers expression in hysteroscopy and hysterectomy specimens from endometrial cancer patients: comparison]. / Porovnání exprese imunohistochemických markeru ve vzorcích z hysteroskopie a hysterektomie u pacientek s karcinomem endometria.

OBJECTIVE: To assess the immunohistochemical expression of p53, bcl-2, c-erbB-2, Ki-67, estrogen (ER) and progesterone receptors (PR), MMP-7, MMP-26 in samplex from diagnostic hysteroscopy and therapeutic hysterectomy in endometrial cancer patients. DESIGN: Experimental prospective study. SETTING: Department of Obstetrics and Gynecology, Institute of Human Genetics, Department of Pathology, Palacky University Medical School and University Hospital, Olomouc. METHODS: We studied 43 cases of primary untreated endometrial carcinoma in which the grade and immunomarkers assessed by histoscore were investigated in specimens obtained at hysteroscopy and hysterectomy. RESULTS: Based on hysterosopy, 31 (72.1%) patients were classified as G1, G2 7 (16.3%) and G3 5 (11.6%) respective. In grade 1 the concordance rate was 77.4% of cases, in grade 2 it was in 14.3% of cases and in grade 3 it was in 80.0% of cases. In hysterosocpy samples the p53 expression was found in 23 (53.5%), bcl-2 in 37 (86.0%), c-erbB-2 in 20 (46.5%), Ki-67 in 29 (67.4%), ER in 37 (86.0%), PR in 36 (83.7%), MMP-7 in 25 (58.1%) and MMP-26 in 23 (53.5%) cases. Expression in hysterectomy specimens was p53 positive in 13 (30.2%), bcl-2 positive in 33 (76.7%), c-erbB-2 positive in 24 (55.8%), Ki-67 positive in 25 (58.1%), ER positive in 36 (83.7%), PR positive in 40 (93.0%), MMP-7 positive in 27 (62.8%) and MMP-26 positive in 23 (53.5%) of total 43 cases. CONCLUSION: We found high concordance in expression of p53, bcl-2, PR and MMP-7 in hysteroscopy and hysterectomy samples which could be of importance for therapeutic algorithm in endometrial cancer patients.