Analysis of the expression of antiangiogenic FKBPL protein, vascular endothelial growth factor and estrogen receptor in uterine endometrioid carcinoma and benign endometrial hyperplasia

ANALIZA EKSPRESIJE ANTIANGIOGENOG FKBPL PROTEINA, VASKULARNOG ENDOTELNOG FAKTORA RASTA I ESTROGENOG RECEPTORA U ENDOMETRIOIDNOM KARCINOMU UTERUSA I BENIGNOJ HIPERPLAZIJI ENDOMETRIJUMA Sažetak Uvod: FKBPL (FK506-binding protein-like), pripada familiji imunofilina, FK506 vezujućih proteina, i predstavlja aktuelno široko ispitivani negativni regulator rasta tumora, angiogeneze i metastaza, sa perspektivom u razvoju ciljane onkološke terapije. Viši nivo ekspresije FKBPL kod pacijenata sa karcinomom dojke je dokazan kao nezavisni prognostički faktor dužeg preživljavanja, kao i dužeg intervala bez relapsa u grupi sa visokom ekspresijom estrogenskog receptora, dok je niži nivo ekspresije FKBPL povezan sa lošijom prognozom preživljavanja. Pokazano je da je povećana ekspresija FKBPL kod pacijenata sa karcinomom dojke praćena nižom ekspresijom estrogenog receptora (ER), većom zavisnošću rasta tumora od estrogene stimulacije i većom senzitivnošću tumora na endokrinu terapiju Tamoksifenom. U okviru predkliničkih studija dokazano je inhibitorno dejstvo FKBPL i njegovih derivata na rast kancerskih stem ćelija karcinoma dojke. Ekspresija FKBPL takođe je ispitivana na kulturama kancerskih stem ćelija karcinoma ovarijuma i ciljana terapija bazirana na FKBPL je pokazala antiangiogeno dejstvo kojim dovodi do usporavanja rasta kolonija stem ćelija karcinoma ovarijuma posredstvom inhibicije migracije endotelnih ćelija. Dokazana je genska ekspresija FKBPL u stromi karcinoma endometrijuma, dok su trenutno jedini izvor o imunohistohemijskoj ekspresiji FKBPL u endometrijumu i karcinomu endometrijuma enciklopedijske baze podataka. Prema dostupnim i relevantnim izvorima, do sada nije izvedena analiza značaja nivoa ekspresije antiangiogenog FKBPL proteina u karcinomima endometrijuma, sa detaljnim sagledavanjem ključnih prognostičkih parametara. Ciljevi: Ciljevi ovog istraživanja su bili da se ispita nivo ekspresije FKBPL, VEGF-A i ER , kao i pojedinačna povezanost nivoa ekspresije VEGF-A i ER sa nivoom eks presije FKBPL, u endometrioidnom karcinomu i benignoj hiperplaziji endometrijuma; da se ispita povezanost nivoa ekspresije FKBPL sa prosečnom gustinom krvnih sudova u endometrioidnom karcinomu i benignoj hiperplaziji endometrijuma; i da se ispita povezanost nivoa ekspresije FKBPL u endometrioidnom karcinomu endometrijuma sa dubinom invazije miometrijuma, prisustvom limfovaskularne invazije, histološkim gradusom tumora i kliničkim stadijumom bolesti. Metode: Studijsku populaciju je činilo 90 slučajeva endometrioidnog karcinoma i 40 slučajeva benigne hiperplazije endometrijuma. Kalupi su izdvojeni iz arhive službe za patologiju a klinički i histološki podaci su dobijeni uvidom u dokumentaciju pacijenata u Kliničko - bolničkom centru Zemun. Imunohistohemijska bojenja na FKBPL, VEGF-A, ERα i CD34 su urađena, prema uputstvima proizvođača, u laboratoriji Instituta za patologiju, Medicinskog fakulteta u Beogradu. Intenziteti ekspresije FKBPL i VEGF-A su izvedena dvostruko slepom analizom od strane dva patologa, kao i morfometrijskom metodom određivanja procenta površine žlezdanog tkiva sa pozitivnom reakcijom antitela. Nivo ERα je određen u okviru dvostruko slepe analize određivanjem intenziteta skalom 0 - 3, procentualne zastupljenosti ERα pozitivnih epitelnih ćelija skalom 0 - 5 i Allered-ovim skorom koji je suma vrednosti prethodne dve skale i u rasponu je 0 - 8. Krvni sudovi obeleženi antitelom CD34 su analizirani određivanjem vaskularne gustine morfometrijskom metodom, na delu uzorka. Morfometrijska merenja su rađena softverom za analizu slike Fiji: an open-source platform for biological-image analysis. Rezultati: Intenzitet ekspresije FKBPL je pokazao statisticki značajno (p<0.001) niže vrednosti u endometrioidnom karcinomu nego u benignoj hiperplaziji endometrijuma, umerenu pozitivnu korelaciju (p<0.05) sa sva tri parametra ekspresije ERα, i umerenu negativnu korelaciju (p<0.05) sa nivoom ekspresije VEGF-A na nivou celog uzorka...ANALYSIS OF THE EXPRESSION OF ANTIANGIOGENIC FKBPL PROTEIN, VASCULAR ENDOTHELIAL GROWTH FACTOR AND ESTROGEN RECEPTOR IN UTERINE ENDOMETRIOID CARCINOMA AND BENIGN ENDOMETRIAL HYPERPLASIA Abstract Background: FKBPL (FK506 binding protein-like), is a divergent member of the immunophilin family, FK506 binding proteins, and is currently a widely studied negative regulator of tumor growth, angiogenesis, and metastasis, with a perspective in the development of targeted therapy in gynecological oncology. A higher level of FKBPL expression in breast cancer patients has been proven to be an independent prognostic factor of longer survival, as well as a longer relapse-free interval in the group with high estrogen receptor expression, while a lower level of FKBPL expression is associated with a worse survival prognosis. It has been shown that increased expression of FKBPL in patients with breast cancer is accompanied by lower expression of ER, greater dependence of tumor growth on estrogen stimulation, and greater sensitivity of tumors to endocrine therapy. In the framework of preclinical studies, the inhibitory effect of FKBPL and its derivatives on the growth of breast cancer stem cells has been proven. The expression of FKBPL was also examined on the cultures of ovarian cancer stem cells and the targeted therapy based on FKBPL showed an antiangiogenic effect, which leads to the slower growth of ovarian cancer stem cell colonies, by inhibiting the migration of endothelial cells. The gene expression of FKBPL in the stroma of endometrial carcinoma has been proven, while currently, the only available source on the immunohistochemical expression of FKBPL in the endometrium and endometrial carcinoma is the encyclopedic human protein database. According to available and relevant sources, there are no publications offering a comprehensive analysis on the subject of expression of the anti-angiogenic FKBPL protein in endometrial cancers has been performed, with a detailed review of the key prognostic parameters. Objectives: The objectives of this study were to examine the expression level of FKBPL, VEGF -A, and ER, as well as the individual association of the expression level of VEGF-A and ER with the expression level of FKBPL, in endometrioid carcinoma and benign endometrial hyperplasia; to examine the association of FKBPL expression levels with vascular density in endometrioid carcinoma and benign endometrial hyperplasia; and to explore the association of FKBPL expression levels in endometrioid endometrial carcinoma with the depth of myometrial invasion, presence of lymphovascular invasion, histological tumor grade and clinical stage of the disease. Methods: The study population consisted of 90 cases of endometrioid carcinoma and 40 cases of benign endometrial hyperplasia. Paraffin molds were obtained from the archives of the pathology service, and clinical and histological data were obtained from patient documentation at the Zemun Clinical Hospital Center. Immunohistochemical stainings for FKBPL, VEGF-A, ERα, and CD34 were performed, according to the manufacturer's instructions, in the laboratory of the Institute of Pathology, Faculty of Medicine in Belgrade. Expression intensities of FKBPL and VEGF-A were performed by double-blind analysis by two pathologists, as well as by the morphometric method of determining the percentage of the glandular tissue surface with a positive antibody reaction. The level of ERα was determined in a double-blind analysis by determining the intensity on a scale of 0- 3, the percentage of ERα-positive epithelial cells on a scale of 0-5, and Allered's score, which is the sum of the values of the previous two scales and is in the range of O-8. Blood vessels labeled with the CD34 antibody were analyzed by determining the vascular density using the morphometric method, on part of the sample. All morphometric measurements were made with Fiji image analysis software: an open-source platform for biological-image analysis. Results: FKBPL expression intensity showed statistically significantly (p<0.001) lower values in endometrioid carcinoma than in benign endometrial hyperplasia, moderate positive correlation (p<0.05) with all three parameters of ERα expression, and moderate negative correlation (p<0.05) with the level of VEGF-A expression observed analyzing the whole sample..

Nonlinear vibration of a nonlocal functionally graded beam on fractional visco-Pasternak foundation

This paper investigates the nonlinear dynamic behavior of a nonlocal functionally graded Euler-Bernoulli beam resting on a fractional visco-Pasternak foundation and subjected to harmonic loads. The proposed model captures both, nonlocal parameter considering the elastic stress gradient field and a material length scale parameter considering the strain gradient stress field. Additionally, the von Karman strain-displacement relation is used to describe the nonlinear geometrical beam behavior. The power-law model is utilized to represent the material variations across the thickness direction of the functionally graded beam. The following steps are conducted in this research study. At first, the governing equation of motion is derived using Hamilton's principle and then reduced to the nonlinear fractional-order differential equation through the single-mode Galerkin approximation. The methodology to determine steady-state amplitude-frequency responses via incremental harmonic balance method and continuation technique is presented. The obtained periodic solutions are verified against the perturbation multiple scales method for the weakly nonlinear case and numerical integration Newmark method in the case of strong nonlinearity. It has been shown that the application of the incremental harmonic balance method in the analysis of nonlocal strain gradient theory-based structures can lead to more reliable studies for strongly nonlinear systems. In the parametric study, it is shown that, on the one hand, parameters of the visco-Pasternak foundation and power-law index remarkable affect the amplitudes responses. On the contrary, the nonlocal and the length-scale parameters are having a small influence on the amplitude-frequency response. Finally, the effects of the fractional derivative order on the system's damping are displayed at time response diagrams and subsequently discussed.This is the peer reviewed version of the article: Nešić, N.; Cajić, M.; Karličić, D.; Obradović, A.; Simonović, J. Nonlinear Vibration of a Nonlocal Functionally Graded Beam on Fractional Visco-Pasternak Foundation. Nonlinear Dynamics 2022, 107 (3), 2003–2026. [https://doi.org/10.1007/s11071-021-07081-z

Analysis of etiological factors and pregnancy outcome in cases of fetal hyperechogenic bowel

Cilj. Prevalenca fetalnog hiperehogenog creva je 0,2 do 1,8%. Cilj ovog istraživanja je bio da se ispitaju etiološki faktori odgovorni za nastanak fetalnog hiperehogenog creva i njihov prognostički značaj na tok i ishod trudnoće, kao i da se preporuči optimalna dijagnostička strategija prilikom kliničkog tretmana ovog poremećaja. Metode. Podaci o prisutnim etiološkim faktorima i ishodu trudnoće prikupljani su telefonskim intervjuisanjem 40 trudnica kod kojih je prilikom rutinskih ultrazvučnih pregleda konstatovano prisustvo fetalnog hiperehogenog creva. Ukupno 12 žena je pristalo da obezbedi potrebne podatke. Njihovi odgovori bili su zasnovani na medicinskoj dokumentaciji, obezbeđenoj tokom njihovih trudnoća. Podaci su analizirani korišćenjem deskriptivne statistike. Rezultati. Najčešći etiološki faktor odgovoran za javljanje fetalnog hiperehogenog creva predstavlja citomegalovirusna infekcija tokom prva dva trimestra trudnoće, dok su prisustvo hromozomskih anomalija i cistična fibroza retko odgovorni za njegov nastanak. U jednom slučaju (8,3%) potvrđeno je prisustvo Daunovog sindroma, u četiri slučaja (33,3%) konstatovana je citomegalovirusna infekcija, dok mutacije u CFTR genu nisu otkrivene ni u jednom slučaju. Ishod trudnoće u svim slučajevima u kojima ultrazvuk pokazuje samo prisustvo fetalne hiperehogenih creva novorođenčeta je bilo živorođeno novorođenče, dok je u slučajevima sa drugim ultrazvučnih nalaza učešće živorođenosti bilo 55 procenata. Zaključak. Ultrazvučni nalaz fetalnog hiperehogenog creva tokom trudnoće predstavlja ozbiljan klinički nalaz koji opravdava primenu invazivnih dijagnostičkih procedura i agresivnu diferencijalno dijagnostičku pretragu.Objective. The prevalence of fetal hyperechogenic bowel is 0.2% to 1.8%. The aim of this study was to examine etiological factors responsible for pathogenesis of fetal hyperechogenic bowel, to investigate their prognostic importance for the progression and outcome of pregnancy and to assess optimal diagnostic strategy of this condition. Methods. The information on etiological factors and pregnancy outcome were collected through telephone interviews with 40 pregnant women with fetal hyperechogenic bowel found on routine ultrasound examination. The total of 12 (30%) women agreed to provide the required information. Their answers were based on medical documentation, provided during their respective pregnancies. Data were analyzed using descriptive statistics. Results. The most common etiological factor in cases of fetal hyperechogenic bowel is infection with cytomegalovirus during the first two trimesters of the pregnancy, while the presence of the chromosome anomalies and cystic fibrosis are responsible for the occurrence of this clinical entity only in a minority of cases. In one of the analyzed cases (8.3%) Down's syndrome was confirmed in fetus, in four cases (33.3%) cytomegalovirus infection was found, while mutations in the CFTR gene were not found in fetus' parents in any of analyzed cases. Outcome of pregnancy in all cases in which the ultrasound examination showed only the presence of fetal hyperechogenic bowel was live newborn, while in cases with other ultrasound findings the contribution of live newborn was 55 percent. Conclusion. Ultrasound of fetal echogenic bowel during pregnancy is a serious clinical condition that justifies the use of invasive diagnostic procedures and aggressive differential diagnostic search

Semiautomatic epicardial fat segmentation based on fuzzy c-means clustering and geometric ellipse fitting

Automatic segmentation of particular heart parts plays an important role in recognition tasks, which is utilized for diagnosis and treatment. One particularly important application is segmentation of epicardial fat (surrounds the heart), which is shown by various studies to indicate risk level for developing various cardiovascular diseases as well as to predict progression of certain diseases. Quantification of epicardial fat from CT images requires advance image segmentation methods. The problem of the state-of-the-art methods for epicardial fat segmentation is their high dependency on user interaction, resulting in low reproducibility of studies and time-consuming analysis. We propose in this paper a novel semiautomatic approach for segmentation and quantification of epicardial fat from 3D CT images. Our method is a semisupervised slice-by-slice segmentation approach based on local adaptive morphology and fuzzy c-means clustering. Additionally, we use a geometric ellipse prior to filter out undesired parts of the target cluster. The validation of the proposed methodology shows good correspondence between the segmentation results and the manual segmentation performed by physicians

The importance of tests applied to evaluate the effectiveness of antiplatelet therapy in patients with recurrent coronary stent thrombosis

Background. Stent thrombosis is potentially lethal complication with huge economic burden. The role of insufficient response to antiplatelet therapy is still unclear reason for its occurrence. Case report. We presented 54-year-old man with recurrent stent thrombosis on the 4th, 9th and 12th day after the primary percutaneous coronary intervention in spite of double antiaggregation therapy (aspirin+ clopidogrel). All possible procedural causes were excluded and reimplantation of intracoronary stent was insufficient to resolve the problem, so four platelet tests were performed: flow cytometry, Platelet Function Analyzer-100 test, aggregometry, and determination of gene polymorphism for P2Y12 receptor (directly involved in the mechanism of thienopyridine), and GPIIbIIIa receptor (final receptor in aggregation). The patient was the carrier of the major haplotype H1H1 for P2Y12 receptor and minor A1A2 for GPIIbIIIa receptor. The results of all the performed tests showed insufficient antiplatelet effect of aspirin and sufficient response to thienopyridin (not to clopidogrel, but to ticlopidine). Conclusion. Performance of platelet function tests is necessary in the case of major adverse cardiac events especially stent thrombosis, after implantation of intracoronary stent

Influence of Dental Restorations on Oxidative Stress in Gingival Crevicular Fluid

Biocompatibility of dental materials (DM) can be evaluated by gingival crevicular fluid (GCF) oxidative stress (OS) status. The goal of the study was to ascertain influence of dental caries degree, teeth position, and type and amount of applied DM on GCF OS profile. For this purpose, we tested six DMs that were sealed in one session: amalgam (Amg), composites: Tetric EvoCeram and Beautifil (BF), phosphate cement-zinc phosphate and polycarboxylate cements zinc polycarboxylate cements, and glass ionomer cement (GIC). The study included 88 dental outpatients. Follow-up was scheduled at 7th and 30th day. Oxidative stress parameters (malondialdehyde (MDA) and glutathione (GSH) levels and total superoxide dismutase (tSOD) activity) were measured before (0th day) and after the treatment (7th and 30th day) in GCF. Control teeth were mirror-positioned healthy teeth. The DM accomplished the following effects (listed in descending order): increase of GSH in GCF was realized by ZPoC > BF > GIC > Amg; tSOD activity increase by ZPoC > BF > Amg; and MDA decrease by ZPoC > ZPhC > Amg > TEC. Dental caries provokes insignificant rise of OS in GCF. ZPoC and ZPhC showed the highest antioxidant effect, contrary to GIC. Restorations with antioxidant properties may reduce gum diseases initiated by caries lesion, what is of great clinical relevance in dentistry

Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a double blind, phase III randomized clinical trial in healthy Serbian adults

This study was a phase III, multicenter, double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a seasonal trivalent split, inactivated influenza vaccine (TIV) in healthy Serbian adults between the ages of 18 and 65 years. This egg-based vaccine was manufactured by the Institute of Virology, Vaccines and Sera, Torlak, Belgrade, Serbia. A total of 480 participants were assigned randomly in a ratio of 2:1 to receive a single intramuscular dose (0.5 ml) of the vaccine (15 µg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Participants were monitored for safety, including solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). No SAEs related to vaccination were reported. Injection site pain (51.3%), injection site tenderness (40.4%), tiredness (17.0%), and headache (15.1%) were the most commonly reported solicited events in the vaccine group. Incidence of related unsolicited AEs was low (1.3%) among vaccinees. Hemagglutinin inhibition (HAI) titers were measured before and 21 days after vaccination in 151 participants. Overall, HAI seroconversion rates to H1 and H3 were observed in 90.1% and 76.2% of vaccinees, respectively. For B antigen, it was 51.5%, likely due to high pre-vaccination titers. Post-vaccination seroprotection rates were in the range of 78.2–95.0% for the three antigens. Post-vaccination geometric mean titers (GMT) were at least 3.8 times higher than baseline levels for all the three strains among vaccinees. Overall, the study showed that the vaccine was safe and well tolerated, and induced a robust immune response against all three vaccine strains., ClinicalTrials.gov identifier: NCT02935192, October 17, 201

Analysis of the expression of antiangiogenic FKBPL protein, vascular endothelial growth factor and estrogen receptor in uterine endometrioid carcinoma and benign endometrial hyperplasia

ANALIZA EKSPRESIJE ANTIANGIOGENOG FKBPL PROTEINA, VASKULARNOG ENDOTELNOG FAKTORA RASTA I ESTROGENOG RECEPTORA U ENDOMETRIOIDNOM KARCINOMU UTERUSA I BENIGNOJ HIPERPLAZIJI ENDOMETRIJUMA Sažetak Uvod: FKBPL (FK506-binding protein-like), pripada familiji imunofilina, FK506 vezujućih proteina, i predstavlja aktuelno široko ispitivani negativni regulator rasta tumora, angiogeneze i metastaza, sa perspektivom u razvoju ciljane onkološke terapije. Viši nivo ekspresije FKBPL kod pacijenata sa karcinomom dojke je dokazan kao nezavisni prognostički faktor dužeg preživljavanja, kao i dužeg intervala bez relapsa u grupi sa visokom ekspresijom estrogenskog receptora, dok je niži nivo ekspresije FKBPL povezan sa lošijom prognozom preživljavanja. Pokazano je da je povećana ekspresija FKBPL kod pacijenata sa karcinomom dojke praćena nižom ekspresijom estrogenog receptora (ER), većom zavisnošću rasta tumora od estrogene stimulacije i većom senzitivnošću tumora na endokrinu terapiju Tamoksifenom. U okviru predkliničkih studija dokazano je inhibitorno dejstvo FKBPL i njegovih derivata na rast kancerskih stem ćelija karcinoma dojke. Ekspresija FKBPL takođe je ispitivana na kulturama kancerskih stem ćelija karcinoma ovarijuma i ciljana terapija bazirana na FKBPL je pokazala antiangiogeno dejstvo kojim dovodi do usporavanja rasta kolonija stem ćelija karcinoma ovarijuma posredstvom inhibicije migracije endotelnih ćelija. Dokazana je genska ekspresija FKBPL u stromi karcinoma endometrijuma, dok su trenutno jedini izvor o imunohistohemijskoj ekspresiji FKBPL u endometrijumu i karcinomu endometrijuma enciklopedijske baze podataka. Prema dostupnim i relevantnim izvorima, do sada nije izvedena analiza značaja nivoa ekspresije antiangiogenog FKBPL proteina u karcinomima endometrijuma, sa detaljnim sagledavanjem ključnih prognostičkih parametara. Ciljevi: Ciljevi ovog istraživanja su bili da se ispita nivo ekspresije FKBPL, VEGF-A i ER , kao i pojedinačna povezanost nivoa ekspresije VEGF-A i ER sa nivoom eks presije FKBPL, u endometrioidnom karcinomu i benignoj hiperplaziji endometrijuma; da se ispita povezanost nivoa ekspresije FKBPL sa prosečnom gustinom krvnih sudova u endometrioidnom karcinomu i benignoj hiperplaziji endometrijuma; i da se ispita povezanost nivoa ekspresije FKBPL u endometrioidnom karcinomu endometrijuma sa dubinom invazije miometrijuma, prisustvom limfovaskularne invazije, histološkim gradusom tumora i kliničkim stadijumom bolesti. Metode: Studijsku populaciju je činilo 90 slučajeva endometrioidnog karcinoma i 40 slučajeva benigne hiperplazije endometrijuma. Kalupi su izdvojeni iz arhive službe za patologiju a klinički i histološki podaci su dobijeni uvidom u dokumentaciju pacijenata u Kliničko - bolničkom centru Zemun. Imunohistohemijska bojenja na FKBPL, VEGF-A, ERα i CD34 su urađena, prema uputstvima proizvođača, u laboratoriji Instituta za patologiju, Medicinskog fakulteta u Beogradu. Intenziteti ekspresije FKBPL i VEGF-A su izvedena dvostruko slepom analizom od strane dva patologa, kao i morfometrijskom metodom određivanja procenta površine žlezdanog tkiva sa pozitivnom reakcijom antitela. Nivo ERα je određen u okviru dvostruko slepe analize određivanjem intenziteta skalom 0 - 3, procentualne zastupljenosti ERα pozitivnih epitelnih ćelija skalom 0 - 5 i Allered-ovim skorom koji je suma vrednosti prethodne dve skale i u rasponu je 0 - 8. Krvni sudovi obeleženi antitelom CD34 su analizirani određivanjem vaskularne gustine morfometrijskom metodom, na delu uzorka. Morfometrijska merenja su rađena softverom za analizu slike Fiji: an open-source platform for biological-image analysis. Rezultati: Intenzitet ekspresije FKBPL je pokazao statisticki značajno (p<0.001) niže vrednosti u endometrioidnom karcinomu nego u benignoj hiperplaziji endometrijuma, umerenu pozitivnu korelaciju (p<0.05) sa sva tri parametra ekspresije ERα, i umerenu negativnu korelaciju (p<0.05) sa nivoom ekspresije VEGF-A na nivou celog uzorka...ANALYSIS OF THE EXPRESSION OF ANTIANGIOGENIC FKBPL PROTEIN, VASCULAR ENDOTHELIAL GROWTH FACTOR AND ESTROGEN RECEPTOR IN UTERINE ENDOMETRIOID CARCINOMA AND BENIGN ENDOMETRIAL HYPERPLASIA Abstract Background: FKBPL (FK506 binding protein-like), is a divergent member of the immunophilin family, FK506 binding proteins, and is currently a widely studied negative regulator of tumor growth, angiogenesis, and metastasis, with a perspective in the development of targeted therapy in gynecological oncology. A higher level of FKBPL expression in breast cancer patients has been proven to be an independent prognostic factor of longer survival, as well as a longer relapse-free interval in the group with high estrogen receptor expression, while a lower level of FKBPL expression is associated with a worse survival prognosis. It has been shown that increased expression of FKBPL in patients with breast cancer is accompanied by lower expression of ER, greater dependence of tumor growth on estrogen stimulation, and greater sensitivity of tumors to endocrine therapy. In the framework of preclinical studies, the inhibitory effect of FKBPL and its derivatives on the growth of breast cancer stem cells has been proven. The expression of FKBPL was also examined on the cultures of ovarian cancer stem cells and the targeted therapy based on FKBPL showed an antiangiogenic effect, which leads to the slower growth of ovarian cancer stem cell colonies, by inhibiting the migration of endothelial cells. The gene expression of FKBPL in the stroma of endometrial carcinoma has been proven, while currently, the only available source on the immunohistochemical expression of FKBPL in the endometrium and endometrial carcinoma is the encyclopedic human protein database. According to available and relevant sources, there are no publications offering a comprehensive analysis on the subject of expression of the anti-angiogenic FKBPL protein in endometrial cancers has been performed, with a detailed review of the key prognostic parameters. Objectives: The objectives of this study were to examine the expression level of FKBPL, VEGF -A, and ER, as well as the individual association of the expression level of VEGF-A and ER with the expression level of FKBPL, in endometrioid carcinoma and benign endometrial hyperplasia; to examine the association of FKBPL expression levels with vascular density in endometrioid carcinoma and benign endometrial hyperplasia; and to explore the association of FKBPL expression levels in endometrioid endometrial carcinoma with the depth of myometrial invasion, presence of lymphovascular invasion, histological tumor grade and clinical stage of the disease. Methods: The study population consisted of 90 cases of endometrioid carcinoma and 40 cases of benign endometrial hyperplasia. Paraffin molds were obtained from the archives of the pathology service, and clinical and histological data were obtained from patient documentation at the Zemun Clinical Hospital Center. Immunohistochemical stainings for FKBPL, VEGF-A, ERα, and CD34 were performed, according to the manufacturer's instructions, in the laboratory of the Institute of Pathology, Faculty of Medicine in Belgrade. Expression intensities of FKBPL and VEGF-A were performed by double-blind analysis by two pathologists, as well as by the morphometric method of determining the percentage of the glandular tissue surface with a positive antibody reaction. The level of ERα was determined in a double-blind analysis by determining the intensity on a scale of 0- 3, the percentage of ERα-positive epithelial cells on a scale of 0-5, and Allered's score, which is the sum of the values of the previous two scales and is in the range of O-8. Blood vessels labeled with the CD34 antibody were analyzed by determining the vascular density using the morphometric method, on part of the sample. All morphometric measurements were made with Fiji image analysis software: an open-source platform for biological-image analysis. Results: FKBPL expression intensity showed statistically significantly (p<0.001) lower values in endometrioid carcinoma than in benign endometrial hyperplasia, moderate positive correlation (p<0.05) with all three parameters of ERα expression, and moderate negative correlation (p<0.05) with the level of VEGF-A expression observed analyzing the whole sample..