Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various tumors, including endometrial carcinomas (EC). However, tumoral receptors that mediate the antiproliferative effects of GHRH antagonists in human ECs have not been fully characterized. In this study, we investigated the expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors (GHRH-R) in 39 human ECs and in 7 normal endometrial tissue samples using RT-PCR. Primers designed for the PCR amplification of mRNA for the full length GHRH-R and SVs were utilized. The PCR products were sequenced, and their specificity was confirmed. Nine ECs cancers (23%) expressed mRNA for SV1, three (7.7%) showed SV2 and eight (20.5%) revealed mRNA for SV4. The presence of SVs for GHRH-Rs could not be detected in any of the normal endometrial tissue specimens. The presence of specific, high affinity GHRH-Rs was also demonstrated in EC specimens using radioligand binding studies. Twenty-four of the investigated thirty-nine tumor samples (61.5%) and three of the seven corresponding normal endometrial tissues (42.9%) expressed mRNA for GHRH ligand. Our findings suggest the possible existence of an autocrine loop in EC based on GHRH and its tumoral SV receptors. The antiproliferative effects of GHRH antagonists on EC are likely to be exerted in part by the local SVs and GHRH system.

Összefoglaló. Bevezetés: Bevezetés: A citológiai alapú méhnyakrákszűrés átmeneti kategóriáinak optimális menedzselése a humán papillomavírus (HPV) szűrése és tipizálása ellenére jelenleg is kihívás. Vizsgálatunk célja a modern cervixspektroszkópiának (multimodális hiperspektroszkópia - MHS), egy azonnali eredményt nyújtó, digitális technológiára épülő módszernek a vizsgálata volt a citológiai alapú méhnyakszűrés találati biztonságának javítására. Betegek és módszer: Vizsgálatainkat 208, 18 és 75 év közötti nőbeteg bevonásával végeztük, akiknél már indikálásra került valamely, a méhnyakon végzendő műtét, citológiai eredményük rendelkezésre állt (a HPV-tesztet, amennyiben nem történt meg, elvégeztük), valamint valamennyi betegnél elvégeztük a műtét előtt az MHS-vizsgálatot. A szövettani mintavétel 166 betegnél történt meg. Eredmények: A citológiai vizsgálatot (az összes betegre tekintve) magas álpozitív arány jellemezte (69,28%), amely megfigyelések mindenképpen utalnak az újabb komponens alkalmazásának igényére a triázsban. Az összes citológiai kategóriára nézve az MHS-eredmények közül kiemelendő az álnegatív leletek rendkívül alacsony aránya (3/166 = 1,8%), mely a HPV-teszt esetén ennél magasabb volt (11/165 = 6,66%). A spektroszkópiás vizsgálat álpozitív aránya ugyanakkor kedvezőtlenebbnek bizonyult (91/166 = 54,81%) a HPV-vizsgálat álpozitív arányánál (40/165 = 24,24%). Az atípusos laphámsejt (ASC-US/ASC-H) citológiai kategória esetén a spektroszkópia álnegatív eredményeinek aránya (3/126 = 2,38%) szintén kedvezőbb volt, mint a HPV-vizsgálaté (9/126 = 7,14%). A cervicalis intraepithelialis neoplasia-2 vagy súlyosabb fokozatú hámelváltozások azonosításában a spektroszkópia szenzitivitása 94% (95% CI = 0,84-0,99), specificitása 22% (95% CI = 0,15-0,31), negatív prediktív értéke 90% (95% CI = 0,73-0,98), pozitív prediktív értéke 34% (95% CI = 0,26-0,43) volt (p = 0,00130). Következtetés: Az MHS fejlett innovatív technológián alapuló, azonnali eredményt adó vizsgálóeljárás, amely kiemelkedően alacsony álnegatív eredménye miatt nagy segítséget nyújt a citológiai eltéréssel rendelkező betegek további vizsgálatában. Orv Hetil. 2021; 162(20): 790-799. SUMMARY: INTRODUCTION:Despite the use of human papillomavirus (HPV) testing, the management of the transitional categories of cytology-based screening still remains a challenge. The modern multimodal hyperspectroscopy (MHS) of the cervix is a novel digital technology based on artificial intelligence, providing an instant result in the assessment of cytology-based screening abnormalities. PATIENTS AND METHODS:208 women (age 18-75) were enrolled. The patients already had cytology results and an operation on the cervix indicated at the time of inclusion. HPV and the hyperspectroscopy examination was performed pre-operatively. The pre-indicated operation was performed on 166 patients. RESULTS:Cytology-based screening alone (in the category of all patients) resulted in a high false-positive rate (69.28%). In this category, the MHS had an outstanding false-negative rate (3/166 = 1.80%) compared to the HPV (11/165 = 6.66%). The false-positive rate of the spectroscopy examination (91/166 = 54.81%) was higher than that of the HPV testing (40/165 = 24.24%). In the atypical squamous cell (ASC-US/ASC-H) category, the false-negative rate of the spectroscopy (3/126 = 2.38%) was also lower than that of the HPV test (9/126 = 7.14%). In the detection of high-grade abnormalities (cervical intraepithelial neoplasia 2 and worse), the spectroscopy had a 94% sensitivity (95% CI = 0.84-0.99), with a 22% specificity (95% CI = 0.15-0.31), an 90% negative predictive value (95% CI = 0.73-0.98), and a 34% positive predictive value (95% CI = 0.26-0.43) (p = 0.00130). CONCLUSION:In the case of cytological abnormality, the MHS provides an immediate result based on advanced digital technology, and because of its outstanding false negative rate it is a great aid and should be considered in the triage of such patients. Orv Hetil. 2021; 162(20): 790-799.

Introduction: Ovarian cancer is the seventh most common cancer in women worldwide with 239,000 new cases estimated to have been diagnosed in 2012. It has the highest mortality among gynaecological malignancies. About 65,000 new cases occur in Europe every year. Nearly 75% of women with ovarian cancer are diagnosed with advanced stage disease.

Introduction/Background The goal of primary debulking surgery (PDS) of ovarian cancer is complete tumour reduction, since any residual tumour disproves overall survival. In later cases neoadjuvant chemotherapy may be an option. We aimed to investigate the use of CA 125 and HE4 preoperative levels in the prediction of complete tumour reduction during upfront surgery, and the use of postoperative marker levels in the verification of complete tumour reduction and progression-free survival (PFS). Methodology 88 advanced ovarian cancer patients (FIGO III-IV), operated between 2010.01.01-2015.12.31 who had attempted curative PDS, had CA 125 and/or HE4 results before and/or after the operation were included. Progression free survival was assessed through Kaplan-Meier analysis, Receiver Operative Characteristics (ROC) curves and area under curve (AUC) was used to evaluate the performance of CA 125 and HE4 markers. Results Preoperative HE4 levels differed significantly in cases of successful complete and incomplete reduction (median [IQR]: 192 [80.1–573.7] vs. 1044 [592.8–2912] respectively, p<0.0001). The ROC analysis gave an AUC of 0.82, and the sensitivity and specificity of complete reduction were 86.67% and 73.33% respectively, at a cut-off level of 496 pmol/l. Preoperative CA 125 proved to be less useful in distinguishing between the two groups. Postoperative HE4 levels differed significantly in the patients who underwent complete reduction from those with residual disease, median [IQR] levels were 54.2 [39.2–82.05] vs. 364.9 [123.3–809.9] respectively (p<0.0001). HE4 also proved more useful in the prediction of >1 year PFS: AUC 0.786 and at a cut-off level of 138, sensitivity and specificity of >1 year PFS were 75% and 75% respectively (p<0.001). Conclusion HE4 proved to be a more useful preoperative tool in the selection of patients for future successful complete reduction. Postoperative HE4 levels might be used as an independent quality assurance marker for the verification of complete reduction and for prediction of PFS. Disclosure Nothing to disclose.

Introduction: Peritoneal dissemination accompanied by ascites formation is common in epithelial ovarian cancer (EOC). Adhesion molecules are crucial in metastatic spread and the latter involves epithelial-mesenchymal transition (EMT). This study aimed at: (1) clarifying whether E-cadherin and beta-catenin expression and proliferative activity in metastatic ovarian cancer are inter-related; (2) Identifying possible correlations between cell adhesion molecular expression profiles, the proliferative activity and p53 expression of tumor cells and tumor grade and stage; (3) testing the cytology microarray (CMA) technique in analyzing metastasis formation. Material and methods: Both tumorous and ascitic samples from 27 EOC patients were examined by using tissue microarray (TMA) and cytology microarray (CMA), respectively. CMA blocks were constructed using cores from each cell block of the ascitic specimens. Expression of E-cadherin, beta-catenin, Ki-67 and p53 was immunohistochemically detected both in TMA and CMA blocks. Results: E-cadherin expression was higher in ascitic cells than in primary tumor cells (p = .294). beta-catenin expression was significantly lower in ascitic cells than in primary tumor cells (p = .006). Expression of Ki-67 was lower and expression of p53 was higher in primary tumors than in ascitic cells, for p53 the difference was significant (p = .001). Both Ki-67 and p53 expression elevated significantly in high-grade primary tumor cells and in ascites cells (p = .039, and p = .004, respectively). Conclusion: Epithelial-mesenchymal transition- mesenchymal-epithelial transition is suggested as the best descriptive term for our IHC observations which accompany increased proliferative activity of ascitic cells. The CMA method is an adequate and reliable method for the analysis of ascitic tumor cells disseminating from ovarian malignancies.

OBJECTIVE:The aim of our study was to evaluate clinical and pathological data in order to draw eligibility criteria for oncologically sufficient radical trachelectomy (RT) in early-stage cervical cancer. Reviewing all cases of attempted RT performed at our unit, we focused attention on prognostic indicators of the need for additional oncologic treatment following RT. The analysis was extended by extensive literature review to include previously published cases of oncologic failures. METHODS:The authors retrospectively analyzed data of patients who underwent RT at the Department of Obstetrics and Gynecology, University of Debrecen. Electronic records and case notes of RT cases were reviewed to determine the incidence of abdominal and vaginal route, distribution of clinicopathologic data, and follow-up results of individual cases. Individual procedures were categorized as oncologically insufficient if additional oncologic treatment was necessary following RT. Theoretical eligibility criteria for RT in early-stage cervical cancer were determined retrospectively by selecting prognostic features that were associated with oncologic insufficiency from clinicopathologic indicators of the complete series. RESULTS:Twenty-four cases of RT were performed by the authors, 15 vaginal RTs with laparoscopic pelvic lymphadenectomy and 9 abdominal RTs with open pelvic lymphadenectomy. Fifteen of 24 cases proved oncologically sufficient. Three cases required immediate conversion to radical hysterectomy because of positive sentinel nodes and/or positive isthmic disc on frozen section. In further 5 cases, final pathology results indicated additional oncologic treatment, that is, radical hysterectomy (n = 2), chemoradiotherapy (n = 2), or chemotherapy (n = 1). One patient among immediately converted cases and another 3 among those who required additional oncologic treatment died of their disease later. There were no other cases of recurrences over a median follow-up of 34 months (range, 12-188 months). Factors that may predict oncologic insufficiency of RT were stage IB1 or greater, tumor size of greater than 2 cm in 1 dimension or greater than 15 mm in 3 dimensions, G3, nonsquamous/adeno histological type, stromal invasion of greater than 9 mm, and lymphovascular space involvement in the primary tumor. CONCLUSIONS:Most cases of oncologically insufficient RTs have significant risk features that can be identified preoperatively. There is a need for more clinicopathologic data on oncologic failure of RT cases in order to improve patient selection.

Two main considerations played roles in creation of new cervical screening system. One was the proven fact that high-risk human papilloma virus infection plays a role in the development of cervical cancer and pre-cancerous lesions. The other was the implementation of the HPV infection's biological behavior in the new screening strategy. The new screening procedure faithfully reflects the cervical carcinogenesis. An organised, population-based and age differentiated screening method could increase attendance of screening and could decrease the possibility of interval cancer rate due to increased sensitivity. Orv Hetil. 2017; 158(52): 2062-2067.

Abstract: Two main considerations played roles in creation of new cervical screening system. One was the proven fact that high-risk human papilloma virus infection plays a role in the development of cervical cancer and pre-cancerous lesions. The other was the implementation of the HPV infection’s biological behavior in the new screening strategy. The new screening procedure faithfully reflects the cervical carcinogenesis. An organised, population-based and age differentiated screening method could increase attendance of screening and could decrease the possibility of interval cancer rate due to increased sensitivity. Orv Hetil. 2017; 158(52): 2062–2067.

Background: Classical features as histomorphology, grade, FIGO stage, and residual tumour mass have strong prognostic value in advanced epithelial ovarian carcinomas (AEOC). Most AEOCs are associated with early recurrence and poor overall survival (OS). Despite of early recurrence, general poor outcome, both high grade tumours or tumours with advanced FIGO stage at the time of diagnosis, in some of such cases, long-term survival (LTS) has been recorded. The aim of this study was to compare the utility of "classical" prognostic factors to molecular factors such as beta-catenin-E-cadherin-, mutated TP53-, and MiB-1 (Ki-67) labelling index determination in predicting long-term survival.Methods: The expression of beta-catenin, E-cadherin, Ki-67, and p53 was determined by immunohistochemistry (IHC) in AEOC. Correlation was sought for between expression of these proteins and the status of classical features vis-a-vis overall survival of patients. Statistical evaluation of the data included Kaplan-Meier analysis, the log-rank test and Cox proportional hazards model.Results: As expected, residual tumour size was an independent adverse prognostic factor for OS (univariate analysis: p = 0.003, multivariate analysis: p = 0.005). Nuclear expression of beta-catenin in advanced ovarian cancer of LTS patients proved to be not only an independent favourable predictor of OS (univariate analysis: p = 0.025, multivariate analysis: p = 0.041) but also showed strong correlation with platinum sensitivity and platinum re-induction.Conclusions: Translocation of stabilized beta-catenin from cytoplasm to the nucleus plays an important role in predicting platinum sensitivity. It also seems to support the chance for platinum re-induction in AEOC and thus enhances long-term survival. (C) 2017 Elsevier GmbH. All rights reserved.

About one‐third of human papillomavirus (HPV) types infect the anogenital tract. High‐risk genital HPV types (such as HPV 16, 18, 31, 33, and 35) are linked causally to the development of cervical cancer. The long control region (LCR) of the HPV genome regulates the replication and transcription of the viral genome. In this study, the functional significance of nucleotide sequence variation within the LCR of HPV 31 was investigated. The LCR was amplified by polymerase chain reaction (PCR) from 41 HPV 31 positive cervical samples of Hungarian women. A phylogenetic tree constructed from the nucleotide sequences of the LCR variants revealed the presence of three intratypic variant lineages of HPV 31, in accordance with previous results. In order to explore the functional consequences of sequence variation in the LCR of HPV 31, selected LCR variants were cloned into a luciferase reporter vector, transfected into C33‐A cells and tested in luciferase reporter assays. Significant differences were found between the transcriptional activities of HPV 31 LCR variants belonging to different variant lineages. As the LCR is governing the transcription of the E6 and E7 oncogenes, the differences in the transcriptional activities of LCR variants may be associated with differences in their oncogenic potential. J. Med. Virol. 85:852–859, 2013. © 2013 Wiley Periodicals, Inc.

Objective Despite the considerable disease burden of ovarian cancer, there were no cost studies in Central and Eastern Europe. This study aimed to describe treatment patterns, health care utilization, and costs associated with treating ovarian cancer in Hungary, Poland, Serbia, and Slovakia. Method Overall clinical practice for management of epithelial ovarian cancer was investigated through a 3-round Delphi panel. Experts completed a survey based on the chart review (n = 1542). The survey was developed based on clinical guidelines and the International Federation of Gynecology and Obstetrics Annual Report. Means, ranges, and outlier values were discussed with the experts during a telephone interview. Finally, consensus estimates were obtained in face-to-face workshops. Based on these results, overall cost of ovarian cancer was estimated using a Markov model. Results The patients included in the chart review were followed up from presurgical diagnosis and in each phase of treatment, that is, surgical staging and primary surgery, chemotherapy and chemotherapy monitoring, follow-up, and palliative care. The 5-year overall cost per patient was €14,100 to €16,300 in Hungary, €14,600 to €15,800 in Poland, €7600 to €8100 in Serbia, and €12,400 to €14,500 in Slovakia. The main components were chemotherapy-associated costs (68%–74% of the total cost), followed by cost of primary treatment with surgery (15%–21%) and palliative care (3%–10%). Conclusions Patients with ovarian cancer consume considerable health care resources and incur substantial costs in Central and Eastern Europe. These findings may prove useful for clinicians and decision makers in understanding the economic implications of managing ovarian cancer in Central and Eastern Europe and the need for innovative therapies.

Background Human epididymis protein 4 (HE4) has recently become an available tumour biomarker for detecting ovarian cancer along with the standard cancer antigen 125 (CA125). However, it is unknown if the levels of HE4 and CA125 may be altered in subjects who have impaired renal function with no ovarian disorders. Methods In 113 female patients at different stages of chronic kidney disease (CKD) with no ovarian and lung cancer and 68 subjects with normal renal and ovarian function, HE4 and CA125 concentrations were analysed by using chemiluminescent microparticle immunoassay (Architect®, Abbott) and electrochemiluminescent immunoassay (Modular E170®, Roche), respectively. Renal function was evaluated by measuring serum creatinine and urea concentrations (Cobas Integra-800®, Roche). Estimated glomerular filtration rate (eGFR in mL/min/1.73 m2) was calculated by the 4v-MDRD formula. Results Significantly increased HE4 concentrations ( P < 0.0001) were found in individuals with differently decreased eGFR values (<90 mL/min/1.73 m2) compared with clinical controls. CA125 serum concentration was higher than normal in subjects with CKD3 (eGFR = 30–59 mL/min/1.73 m2), but significant elevation ( P = 0.006) in CA125 concentrations was seen only in those who had severe renal failure (CKD4-5; eGFR < 30 mL/min/1.73 m2). These tendencies were independent of age in our study cohort, and seemed to be more evident among women in premenopausal status. Conclusions HE4 concentrations may be elevated in CKD patients with no ovarian and lung cancer. Thus, HE4 results should be interpreted cautiously in women with renal disorders.

Emotions are parts of organizational reality to an ever increasing extent. Importantly, they are not just tools in the hand of healthcare workers to achieve better physician / healthcare professional-to-patient interactions but intrinsic processes and characteristics with psychic, cognitive and somatic actions. For a thorough investigation of the issue, a PANAS-X questionnaire was used to examine the emotions of 187 physicians and other healthcare professionals, all engaged in oncology, in 2009. The research succeeded in exploring the overall emotional state oncology professionals had assumed in relation with their job as well as enabled the authors of this study to draw the respondents' emotional map and assess their fundamental emotional attitudes. Furthermore, the authors managed to identify groups of respondents that had felt more intense positive, and/or less intense negative emotions that are socially accepted than others. They included those of senior experienced oncologists, males, individuals with families, childless individuals, ward workers, and skilled professionals. According to the findings, the range of emotions an oncologist experiences / feels intently during his everyday work is dependent upon a great number of factors.

P-glycoprotein (Pgp, ABCB1) is one of the active efflux pumps that are able to extrude a large variety of chemotherapeutic drugs from the cells, causing the phenomenon of multidrug resistance. It has been shown earlier that the combined application of a class of Pgp modulators (e.g. cyclosporine A and SDZ PSC 833) used at low concentrations and UIC2 antibody is a novel, specific, and effective way of blocking Pgp function (Goda et al., 2007). In the present work we study the UIC2 antibody mediated Pgp inhibition in more detail measuring the accumulation of tumor diagnostic radiotracers, 2-[F-18]fluoro-2-deoxy-D-glucose ((18)FDG) and [Tc-99m]hexakis-2-methoxybutyl isonitrile (Tc-99m-MIBI), into Pgp(+) (A2780AD) and Pgp(-) (A2780) human ovarian carcinoma cells.Co-incubation of cells with UIC2 and cyclosporine A (CSA, 2 mu M) increased the binding of UIC2 more than 3-fold and reverted the rhodamine 123 (R123), daunorubicin (DNR) and Tc-99m-MIBI accumulation of the Pgp(+) 2780AD cells to approx. the same level as observed in Pgp(-) cells. Similarly, 50 mu M paclitaxel (Pacl) increased UIC2 binding, and consequently reinstated the uptake of R123. DNR and Tc-99m-MIBI into the Pgp(+) cells. Blocking Pgp by combined treatments with CSA + UIC2 or Pad l + UIC2 also decreased the glucose metabolic rate of the A2780AD Pgp(+) cells measured in (18)FDG accumulation experiments suggesting that the maintenance of Pgp activity requires a considerable amount of energy. Similar treatments of the A2780 Pgp(-) cells did not result in significant change in the R123, DNR, Tc-99m-MIBI and (18)FDG accumulation demonstrating that the above effects are Pgp-specific. Thus, combined treatment with the UIC2 antibody and Pgp modulators can completely block the function of Pgp in human ovarian carcinoma cells and this effect can be followed in vitro by using tumor-diagnostic radiotracers, Tc-99m-MIBI and (18)FDG. (C) 2010 Elsevier B.V. All rights reserved.

We studied how very short (10–40 min) incubation with anthracycline derivatives modifies the accumulation of PET tumor-diagnostic radiotracers in cancer cells. The human ovarian A2780 and A2780AD, human B lymphoid JY, human epidermoid KB-3-1 and KB-V-1, and smooth muscle DDT1 MF-2 cells were pre-incubated with daunorubicin and doxorubicin, and the uptake of [18F]FDG and [11C]choline was measured. Anthracycline treatment decreased remarkably the [11C]choline accumulation in a concentration dependent manner, while it did not modify significantly the [18F]FDG uptake of the cells.