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Introduction: Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers., Methods: This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data., Results: Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations., Conclusion: We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice., Introduction: Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers., Methods: This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data., Results: Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations., Conclusion: We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Breast cancer is the most commonly occurring cancer worldwide and is the main cause of death from cancer in women. Novel biomarkers are highly warranted for this disease., Objective: Evaluation of novel long non-coding RNAs biomarkers for breast cancer., Methods: The study comprised the analysis of the expression of 71 candidate lncRNAs via screening, six of which (four underexpressed, two overexpressed) were validated and analyzed by qPCR in tumor tissues associated with NST breast carcinomas, compared with the benign samples and with respect to their clinicopathological characteristics., Results: The results indicated the tumor suppressor roles of PTENP1, GNG12-AS1, MEG3 and MAGI2-AS3. Low levels of both PTENP1 and GNG12-AS1 were associated with worsened progression-free and overall survival rates. The reduced expression of GNG12-AS1 was linked to the advanced stage. A higher grade was associated with the lower expression of PTENP1, GNG12-AS1 and MAGI2-AS3. Reduced levels of both MEG3 and PTENP1 were linked to Ki-67 positivity. The NRSN2-AS1 and UCA1 lncRNAs were overexpressed; higher levels of UCA1 were associated with multifocality., Conclusions: The results suggest that the investigated lncRNAs may play important roles in breast cancer and comprise a potential factor that should be further evaluated in clinical studies.

Introduction: Breast cancer is the most common cancer and the leading cause of cancer death in women. Recent research indicates that human endogenous retroviruses (HERVs) may be linked to carcinogenesis, but the data remain controversial., Methods: HERVs' expression was evaluated to show the differences between breast cancer and control samples, and their associations with clinicopathological parameters. Gene expression of 12 HERVs, i.e., ERVE-4, ERVW-1, ERVFRD-1, ERVV-1, ERV3-1, ERVH48-1, ERVMER34-1, ERVK-7, ERVK13-1, ERVK11-1, ERVK3-1, and HCP5, was analyzed by qPCR and/or TCGA datasets for breast cancer., Results: ERV3-1, ERVFRD-1, ERVH48-1, and ERVW-1 provided data to support their tumor suppressor roles in breast cancer. ERV3-1 evinced the best performing diagnostic data based on qPCR, i.e., , Auc: 0.819 (p < 0.0001), sensitivity of 72.41%, and specificity of 89.66%. Lower levels of ERV3-1 were noted in advanced stage and higher grades, and significant negative association was found in relation to Ki-67 levels. Oncogenic roles may be inferred for ERVK13-1, ERVV-1, and ERVMER34-1. Data for ERVK-7, ERVE-4, ERVK11-1, and HCP5 remain inconclusive., Conclusion: Differential HERV expression may be applicable to evaluate novel biomarkers for breast cancer. However, more research is needed to reveal their real clinical impact, the biological roles, and regulatory mechanisms in breast carcinogenesis., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Breast cancer is a leading cause of cancer-related death in women. Most cases are invasive ductal carcinomas of no special type (NST breast carcinomas)., Methods and Results: In this prospective, multicentric biomarker discovery study, we analyzed the expression of small non-coding RNAs (mainly microRNAs) in plasma by qPCR and evaluated their association with NST breast cancer. Large-scale expression profiling and subsequent validations have been performed in patient and control groups and compared with clinicopathological data. Small nuclear U6 snRNA, miR-548b-5p and miR-451a have been identified as candidate biomarkers. U6 snRNA was remarkably overexpressed in all the validations, miR-548b-5p levels were generally elevated and miR-451a expression was mostly downregulated in breast cancer groups. Combined U6 snRNA/miR-548b-5p signature demonstrated the best diagnostic performance based on the ROC curve analysis with AUC of 0.813, sensitivity 73.1% and specificity 82.6%. There was a trend towards increased expression of both miR-548b-5p and U6 snRNA in more advanced stages. Further, increased miR-548b-5p levels have been partially associated with higher grades, multifocality, Ki-67 positivity, and luminal B rather than luminal A samples. On the other hand, an association has been observed between high miR-451a expression and progesterone receptor positivity, lower grade, unifocal samples, Ki-67-negativity, luminal A rather than luminal B samples as well as improved progression-free survival and overall survival., Conclusions: Our results indicated that U6 snRNA and miR-548b-5p may have pro-oncogenic functions, while miR-451a may act as tumor suppressor in breast cancer., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Ovarian cancer comprises the most lethal gynecologic malignancy and is accompanied by the high potential for the incidence of metastasis, recurrence and chemotherapy resistance, often associated with a formation of ascitic fluid. The differentially expressed ascites-derived microRNAs may be linked to ovarian carcinogenesis. The article focuses on a number of miRNAs that share a common expression pattern as determined by independent studies using ascites samples and with regard to their functions and outcomes in experimental and clinical investigations.Let-7b and miR-143 have featured as tumor suppressors in ovarian cancer, which is in line with data on other types of cancer. Although two miRNAs, i.e. miR-26a-5p and miR-145-5p, act principally as tumor suppressor miRNAs, they occasionally exhibit oncogenic roles. The performance of miR-95-3p, upregulated in ascites, is open to debate given the current lack of supportive data on ovarian cancer; however, data on other cancers indicates its probable oncogenic role. Different findings have been reported for miR-182-5p and miR-200c-3p; in addition to their presumed oncogenic roles, contrasting findings have indicated their ambivalent functions. Further research is required for the identification and evaluation of the potential of specific miRNAs in the diagnosis, prediction, treatment and outcomes of ovarian cancer patients.

High grade serous carcinoma of the ovary, fallopian tube, and peritoneum (HGSC) is the deadliest gynecological disease which results in a five-year survival rate of 30% or less. HGSC is characterized by the early and rapid development of metastases accompanied by a high frequency of ascites i.e. the pathological accumulation of fluid in peritoneum. Ascites constitute a complex tumor microenvironment and contribute to disease progression by largely unknown mechanisms. Methods: Malignant ascites obtained from HGSC patients who had undergone cytoreductive surgery were tested for their ability to induce WNT signaling in the Kuramochi cell line, a novel and clinically relevant in vitro model of HGSC. Next, cancer spheroids (the main form of metastatic cancer cells in ascites) were evaluated with respect to WNT signaling. Kuramochi cells were used to determine the role of individual WNT signaling branches in the adoption of metastatic stem cell-like behavior by HGSC cells. Furthermore, we analyzed genomic and transcriptomic data on WNT/Planar Cell Polarity (PCP) components retrieved from public cancer databases and corroborated with primary patient samples and validated antibodies on the protein level. Results: We have shown that ascites are capable of inducing WNT signaling in primary HGSC cells and HGSC cell line, Kuramochi. Importantly, patients whose ascites cannot activate WNT pathway present with less aggressive disease and a considerably better outcome including overall survival (OS). Functionally, the activation of non-canonical WNT/PCP signaling by WNT5A (and not canonical WNT/β-catenin signaling by WNT3A) promoted the metastatic stem-cell (metSC) like behavior ( i.e. self-renewal, migration, and invasion) of HGSC cells. The pharmacological inhibition of casein kinase 1 (CK1) as well as genetic ablation (dishevelled 3 knock out) of the pathway blocked the WNT5A-induced effect. Additionally, WNT/PCP pathway components were differentially expressed between healthy and tumor tissue as well as between the primary tumor and metastases. Additionally, ascites which activated WNT/PCP signaling contained the typical WNT/PCP ligand WNT5A and interestingly, patients with high levels of WNT5A protein in their ascites exhibited poor progression-free survival (PFS) and OS in comparison to patients with low or undetectable ascitic WNT5A. Together, our results suggest the existence of a positive feedback loop between tumor cells producing WNT ligands and ascites that distribute WNT activity to cancer cells in the peritoneum, in order to promote their pro-metastatic features and drive HGSC progression. Conclusions: Our results highlight the role of WNT/PCP signaling in ovarian cancerogenesis, indicate a possible therapeutic potential of CK1 inhibitors for HGSC, and strongly suggest that the detection of WNT pathway inducing activity ascites (or WNT5A levels in ascites as a surrogate marker) could be a novel prognostic tool for HGSC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Ovarian cancer as the most fatal gynecological malignancy is often manifested by excessive fluid accumulation known as ascites or effusion. Ascites-derived microRNAs (miRNAs) may be closely associated with ovarian cancer progression. However, our knowledge of their roles, altered expression, and clinical outcomes remained limited. In this study, large-scale expression profiling of 754 human miRNAs was performed using real-time quantitative polymerase chain reaction and 384-well TaqMan array human miRNA A and B cards to identify differentially expressed miRNAs between extracellular fraction of the ascitic fluid associated with high-grade serous ovarian carcinomas and control plasma. Of the 754 miRNAs, 153 were significantly differentially expressed relative to the controls. Expression of 7 individual miRNAs (miR-200a, miR-200b, miR-200c, miR-141, miR-429, miR-1290, and miR-30a-5p) was further validated in extended sample sets, including serous, endometrioid, and mucinous subtypes. All miR-200 family members and miR-1290 were conspicuously overexpressed, while miR-30a-5p was only weakly overexpressed. The ability of miRNAs expression to discriminate the pathological samples from the controls was strong. Receiver operating characteristic curve analyses found area under the curve (AUC) values of 1.000 for miR-200a, miR-200c, miR-141, miR-429, and miR-1290 and of AUC 0.996 and 0.885 for miR-200b and miR-30a-5p, respectively. Preliminary survival analyses indicated low expression level of miR-200b as significantly related to longer overall survival (hazard ratio [HR]: 0.25, mean survival 44 months), while high expression level was related to poor overall survival (HR: 4.04, mean survival 24 months). Our findings suggested that ascites-derived miRNAs should be further explored and evaluated as potential diagnostic and prognostic biomarkers for ovarian cancer.

Ovarian cancer is the deadliest gynecologic cancer. The large-scale microRNA (miRNA) expression profiling and individual miRNA validation was performed to find potential novel biomarkers for ovarian cancer. The most consistent overexpression of miRs-200b-3p, 135 b-5p and 182-5p was found in both ascitic fluid and tumors and suggests their potential as oncogenes. miR-451a was consistently underexpressed so may be a tumor suppressor. Results were inconsistent for miR-204-5p, which was overexpressed in ascitic fluid but underexpressed in tumor tissue. miR-203a-3p was generally overexpressed but this failed to be proved in independent sample set in tissue validation.

Background: Cervical cancer is the fourth most common cancer in women and is usually associated with human papillomavirus infection. Viral infections are usually characterized by morphological changes of epithelial cells; however, it is difficult to determine using recently available screening methods whether the changes are caused by productive infection or by malignant disease. Thus, new efforts are required to find novel diagnostic biomarkers of cervical cancer, such as miRNAs, which are small non-coding RNAs involved in the regulation of gene expression., Materials and Methods: miR-34c levels in cervical cancer cell lines were determined by the droplet-digital polymerase chain reaction. Changes in miR-34c expression in vitro were achieved by transient transfection with a specific miRNA mimic and inhibitor oligonucleotides. Cell proliferation was analyzed by crystal violet staining followed by spectrophotometric measurements. The effect on migratory properties was studied using a „scratch“ assay. Western blotting analysis was used to determine the expression of selected proteins., Results: The downregulation of miR-34c expression was associated with a slight increase in cellular proliferation and a significant increase in cell migration. The analysis of miR-34c expression performed on a set of 39 dysplastic tissues and 35 samples of healthy controls subsequently revealed a significant difference (p < 0.01) in the level of this miRNA., Conclusion: Comparative expression analysis revealed lower expression of miR-34c in cervical precanceroses than in normal untransformed epithelium. in vitro modulation of miR-34c expression revealed its tumor suppressor role in cervical  malignancies. Key words: cervical cancer - HPV - miRNA - HSIL - hsa-miR-34c - precancerosis This work was supported by the projects MEYS - NPS I - LO1413, P206/12/G151 and MH CZ - DRO (MMCI, 00209805). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.  The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Accepted: 16. 7. 2018.

Objective: The aim of the study was to describe the role of hormonal therapy in the treatment of malignant uterine tumors, indications, the effect of the treatment and to verify its safety in our study cohort. We also present an overview of recent studies on that topic., Design: Unicentric retrospective observational study and review of recent literature., Setting: Department of Obstetrics and Gynecology, Masaryk University, University Hospital Brno., Methods: The results of recent relevant studies and reviews published in English until December 2017 were used for the review. The publications were searched using the PubMed server. All patients diagnosed in our oncogynecological center between 2010 and 2016 and who were treated hormonally - either in primary therapy or in relapse settings, were included in our study. We were interested in age, BMI, stage of disease, histological type and grade of tumor, occurrence of adverse effects, duration of survival, reasons for choosing hormonal therapy. Medroxyprogesterone-acetate or megestrol-acetate was used in the treatment., Results: Between 2010 and 2016, 415 malignant tumors of the uterus were diagnosed in our oncology center. Recurrence of the disease occurred in 31 patients (8%), on average 16 months after primary treatment. Primary hormonal therapy was used in only 19 patients (5%), mostly because of contraindications of another treatment due to high age, comorbidities or obesity. Median age of patients was 83 years, mean BMI 41, median survival of patients who died was 8 months. Five patients (16%) were treated hormonally for the recurrence. Median survival from diagnosis of recurrence was 20 months. One patient (4%) experienced partial pulmonary embolism., Conclusion: Hormonal therapy plays an irreplaceable role in uterine cancer patients, especially in primary non-operable patients, in treatment of a relapse, or in a fertility-sparing procedure. This treatment option is safe, with minimal adverse effects.

Aims: To describe the ultrasound features of benign struma ovarii that often mimic ovarian cancer in the background of complex clinical and histopathological pictures., Material and Methods: We retrospectively identified patients with histologically confirmed benign struma ovarii, treated in our institution between 2003-2016 with complete imaging, clinical, nd histopathological data available. Ultrasound findings were drawn from images, and reports using terms and definitions of the International Ovarian Tumor Analysis group and pattern recognition description was applied., Results: In all, 19 patients were identified; 10 with pure and 9 with impure struma. Median age was 47 (range 24-69); 10 (53%) were premenopausal. Only four (21%) patients presented with pain, others were asymptomatic. Using pattern recognition, 74% strumas (14/19) were uni-/multilocular solid or solid tumors. The solid components were roundish with smooth contours. Six struma pearls were detected. The subjective color score was moderate or abundant in the majority of solid components. Only 5 (26%) tumors were purely cystic., Conclusions: The ultrasound characteristics differ widely from typical mature ovarian teratoma. Features such as, solid roundish components with smooth contours, struma pearls, acoustic shadowing and occasionally signs of dermoid are clues and may help preoperatively to differentiate benign struma from malignant adnexal lesions.

Objectives: To describe the ultrasound features of benign Brenner tumor in the background of complex clinical and histopathological pictures., Material and Methods: We retrospectively identified patients with histologically confirmed benign Brenner tumor of the ovary who were treated in our institution in 2003-2016, and for whom complete imaging, clinical, perioperative and histopathological data were available in the database. Ultrasound findings were drawn from images and reports using terms and definitions of the International Ovarian Tumor Analysis group and pattern recognition description was applied., Results: Twenty-three patients were identified, most postmenopausal and asymptomatic. On ultrasound, 19/23 tumors were found unilaterally, 4/23 bilaterally, and 82% of tumors were detected in the left ovary. Most Brenner tumors (16/23) contained solid components and revealed no or minimal blood flow by subjective color score upon Doppler examination (19/23, 83%). Calcifications with shadowing were observed in 57% of all Brenner tumors and in 81% of tumors containing solid components. The complex appearance of the tumor misled the sonographers to describe the mass as malignant in 9 cases (39%), and frozen section was performed perioperatively. Surgery was performed via laparoscopy in 11 (48%) and via laparotomy in 12 (52%) cases., Conclusions: The complexity of the ultrasound picture, consisting of features like calcifications with acoustic shadowing, a poorly vascularized solid mass, and a left-sided localization could be signs of a benign Brenner tumor and could preop-eratively help to differentiate between benign and malignant tumor.

Introduction: Pelvic high-grade serous carcinomas (HGSCs) include carcinoma of ovary, fallopian tube, and peritoneum. Five-year survival, irrespective of the stage, is between 35-40%. Most patients are diagnosed in advanced stages of the disease. The new revised and expanded dualistic model of ovarian carcinogenesis shows that type II tumors are composed for the most part of high-grade serous ovarian carcinoma, carcinosarcoma, undifferentiated carcinoma and can be further subdivided into morphologic and molecular subtypes. Many type II carcinomas develop from STIC predominantly in the distal portion of the fallopian tube and it is very likely the point of the origin of a significant subset of the pelvic high-grade serous carcinomas., Objective: To provide an overview of major changes in our understanding of the origin of ovarian cancer, that led to the revision of FIGO (International Federation of Gynecology and Obstetrics) classification and its unification for the ovary, fallopian tube and peritoneum. We summarize the new classification, main changes compared to the former one and their clinical impact., Methods: For this review, we have used the results of studies and review articles on the subject published in English up to October 2016. They were identified through a search of literature using PubMed, MEDLINE-Ovid, Scopus and Cochrane Library with the keywords ("serous tubal intraepithelial carcinoma" or "high-grade serous ovarian carcinoma" or "FIGO ovarian cancer staging 2014"). We retrieved and assessed potentially relevant studies, and checked the reference lists of all papers of interest to identify additional relevant publications., Conclusion: The origin of most cases of pelvic HGSC (carcinoma of ovary, the fallopian tube, and peritoneum) is expected in the fallopian tube epithelium. The main changes in the revised FIGO classification for extrauterine pelvic serous carcinomas were subdivision of stages IC, III and IV and elimination of the stage IIC, based on new knowledge and prognostic data. A prerequisite for the proper treatment of patients is to perform adequate surgical and pathological staging, including determining the grade of carcinoma. These factors, coupled with appropriately performed operation with zero postoperative residuum (R0), are the most important prognostic factors for patients with carcinoma of the ovary, fallopian tube, and peritoneum.

Introduction: Octreotide is a synthetic analogue of natural somatostatin. Octreotide effect on lymphorrhea reduction in gynecological malignancies has only been assessed in case studies., Design: Original work., Setting: Gynecologic Oncology Center, Department of Obstetrics and Gynecology, Faculty of Medicine, Masaryk University and University Hospital Brno., Methods: In 2014 there was a prospective, randomized, one-institution study. Patients underwent surgery including pelvic or pelvic and paraaortic lymphadenectomy for cervical, uterine and ovarian cancer. The informed consent was signed. Octreotide was evaluated in relation to diagnosis, surgery (laparoscopy versus laparotomy), pelvic and/or paraaortic lymphadenectomy, number of removed lymph nodes and their positivity, neoadjuvant chemotherapy, adjuvant chemotherapy, adjuvant radiotherapy, albumin, BMI, number of days with drains postoperatively, number of days in hospital, blood loss during surgery, time of surgery, total number of drains placed into abdominal cavity. In follow up period, within 1 year after surgery, we searched for lymphocele, lymph-edema of lower extremities and lymphatic ascites in relation to lymphorrhea., Results: 44 patients (9 cervical, 19 endometrial and 16 ovarian cancer) were enrolled in two statistically comparable randomized groups. "Octreotide group", which paradoxically showed lymphorrhea of 4082 ml on average, (without 1992 ml, p = 0.001), needed drainage for more days (p = 0.001). The diagnosis had no influence on lymphorrhea in both groups (p = 0.966). The neoadjuvant chemotherapy was administered (p = 0.026), the more lymph nodes were removed (p = 0.018), the more days the drainage was in place (p < 0.001), the bigger the lymphorrhea; no relationship between lymphorrhea and age (p = 0.631), albumin level (p = 0.584), BMI ( p= 0.966) or number of positive nodes (p = 0.259), length of surgery (p = 0.206), blood loss (p = 0.494). Nor lymphedema (p = 0.404), nor lymphocele (p = 0.086), correlated with postoperative lymphorrhea. Lymphatic ascites was associated with lymphorrhea (p = 0.048)., Conclusion: Octreotide did not reduce lymphorrhea and the incidence of lymphocele, lymphedema of lower extremities and lymphatic ascites within one year of follow-up period after surgery. According to our results, we do not recommend to administer the octreotide in oncogynecological patients after pelvic and/or paraaortic lymphadenectomy.

Objective: To review the incidence of histologic variants of uterine fibroids of patients in reproductive age and postmenopause. Analysis of potential relations between histological fibroids variants and hormonal activity of the patient., Design: Retrospective analysis., Setting: Department of Obstetrics and Gynecology, Masaryk University and University Hospital Brno., Material and Methods: Retrospective analysis of 2,397 women who underwent myomectomy or hysterectomy at the Department of Obstetrics and Gynecology, Masaryk University and University Hospital Brno in years 2008-2014. According to input criteria - age of patients between 18-65 years, ultrasound confirmed uterine fibroid. Exclusion criteria was irregular menstrual cycle, hormonal therapy in history or hysterectomy performed for tumors of the small pelvis or for cancer of the uterus or cervix.Group A consisted of 235 patients with regular menstrual cycles, between ages 18-40. Myomectomy was chosen for these patients.Group B consisted of 433 postmenopausal patients between ages 50-65. Laparoscopic and abdominal hysterectomy was performed to these patients., Results: A statistically significant difference was observed in the occurrence of epithelioid type of leiomyoma between women age groups 18-40 and 50-65. In the group of postmenopausal women four malignant forms of leiomyoma were recorded, which were not statistically relevant., Conclusion: After evaluating statistical analysis it was found, that there is a statistically significant difference in epithelioid type of uterine leiomyoma. Four patients were detected malignant variant of leiomyoma - leiomyosarcoma in the group of postmenopausal women.

Among gynaecological cancers, epithelial ovarian cancers are the most deadly cancers while endometrial cancers are the most common diseases. Efforts to establish relevant novel diagnostic, screening and prognostic markers are aimed to help reduce the high level of mortality, chemoresistance and recurrence, particularly in ovarian cancer. MicroRNAs, the class of post-transcriptional regulators, have emerged as the promising diagnostic and prognostic markers associated with various diseased states recently. Urine has been shown as the source of microRNAs several years ago; however, there has been lack of information on urine microRNA expression in ovarian and endometrial cancers till now. In this pilot study, we examined the expression of candidate cell-free urine microRNAs in ovarian cancer and endometrial cancer patients using quantitative real-time PCR. We compared the expression between pre- and post-surgery ovarian cancer samples, and between patients with ovarian and endometrial cancers and healthy controls, within three types of experiments. These experiments evaluated three different isolation methods of urine RNA, representing two supernatant and one exosome fractions of extracellular microRNA. In ovarian cancer, we found miR-92a significantly up-regulated, and miR-106b significantly down-regulated in comparison with control samples. In endometrial cancer, only miR-106b was found down-regulated significantly compared to control samples. Using exosome RNA, no significant de-regulations in microRNAs expression could be found in either of the cancers investigated. We propose that more research should now focus on confirming the diagnostic potential of urine microRNAs in gynaecological cancers using more clinical samples and large-scale expression profiling methods.

Objective: The aim of the present study was to evaluate the use of human epididymis protein 4 (HE4) and cancer antigen 125 (CA 125) biomarkers in differential diagnosis of malignant and benign endometrial tumours in a population of Czech women., Design: Prospective study., Setting: Department of Gynaecology and Obstetrics, Faculty of Medicine at Masaryk University and Faculty Hospital in Brno., Methods: Our prospective study includes 115 patients with endometrioid adenocarcinoma and 106 patients with benign endometrial tumours in the control group. They were diagnosed with endometrial biopsy in the period from 7/2010 to 6/2013. The patients with cancer underwent definitive surgical treatment to determine the stage of disease. The median and ranges of serum levels were determined in relation to the histological result (benign vs malignant disease). Statistical analysis operates with logarithm values of markers because their distribution is not normal and uses logistic regression., Results: While analysing two groups of patients with different histology, there was demonstrated a statistically significant difference (p < 0.05), only in HE4, by cut-off 48,5 pmol/l there was achieved sensitivity of 87.8%, specificity of 56.6% and negative predictive value of 81.1%., Coclusion: Diagnostic benefit of HE4 can be considered especially in patients with increased risk of endometrial cancer and in patients with serious internal co-morbidities. HE4 could help in combination with clinical and ultrasound finding in the differentiation of prognostically various groups of patients and in decision-making in relation to the individualization of the treatment plan. However, the optimal cut-off for HE4 has not been solved yet, and to do so, it will require more research with larger studies and their comparative analysis..

Objective: Ovarian epithelial malignant tumors in adolescence., Design: Literature review with case reports., Setting: Department of Gynaecology and Obstetrics, Faculty of Medicine at Masaryk´s University and Fakulty Hospital Brno., Methods: Literature review on ovarian epithelial malignant tumors in adolescence, their epidemiology, diagnosis and therapy with illustrative case reports., Conclusion: The ovarian epithelial malignant tumors in the adolescence represent rare group of these diseases according to the data from the National Cancer Registry. However, it is a very sensitive area of oncogynecology, that requires highly personalized approach and the cooperation with patient´s family. The ovarian epithelial malignant tumors in the age group of 15-19 years show some differences from these diseases of adults and older women. The differences concern the extent of the disease at the time of the diagnosis, the histopathological characteristics of the tumors and the proportion surgical therapy and chemotherapy. The diagnostic algorithm requires the cooperation with the colleagues from pediatric gynecology and oncology. Due to the occurrence of localizated stages and good tumor differentiation prevails the monotherapy presented the surgical treatment, especially in the form of the radical fertility-preserving procedures. The care of the patients should be concentrated into the oncogynecological centres.

Ovarian cancer is the most malignant and the second most common gynecological cancer which encompasses a heterogeneous group of tumors with a different etiology. Extra-ovarian tissues may play a role in the development of ovarian cancer, despite this issue is still debated. This disease is associated with a strong chemoresistance and tendency to recurrence, and asymptomatic behaviour at early stages. Effective screening markers have not been established yet. Cancer stem cells have been postulated to play a role within tumor formation and by the establishment of chemotherapy-resistant population of malignant cells after the surgery and application of chemotherapy. These cells are multipotent cells capable of un-limited divisions and have potential to induce tumorigenesis in immune-suppressed mice. Their detailed characterization is still an open issue, however there have been identified several markers associated with ovarian cancer stem cells. The major markers of ovarian cancer stem cells identified so far are CD133, ALDH, CD44, CD117, CD24 and EpCAM. Their occurrence in primary tumors may be associated with patients´ prognosis; however there are insufficient data for definite conclusions. Dynamic processes of carcinogenesis result also in changes of cancer stem cells phenotypes based on the microenvironmental changes within the tumor. The markers may thus be acquired, or lost, as it has been proven experimentally. As regards the possibility to use targeted, specific therapy approaches, there are some promising studies, suggesting this may be a method of potential treatment. Further characterization and functional studies of cancer stem cells will be necessary for the elucidation of carcinogenesis, chemoresistance and metastases formation-associated processes. Such studies will be the basis for establishment of novel diagnostic, prognostic and therapeutic approaches for the ovarian cancer treatment. The most recent results on ovarian cancer stem cells research are presented in this paper.

Objective: Presentation of the file prognostically highly unfavourable group cancers of breast., Design: Retrospective analysis., Setting: Department of Gynaecology and Obstetrics, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno., Methods: In the study, we retrospectively analyzed 47 patients with triple negative breast cancer, who have undergone in the period 2005-2008 complete treatment and then follow-up in Department of Gynaecology and Obstetrics, Faculty of Medicine, Masaryk University and Faculty Hospital, Brno. 2/3 patients underwent primary surgery followed by adjuvant therapy, 1/3 patients underwent neoadjuvant chemotherapy followed by surgery and eventually adjuvant therapy. Then patients were transferred to follow-up., Results: Approximatelly 2/3 patients were diagnosed in early stages I and IIA FIGO, other patients in advanced stages, even though almost 90% of women participated regularly in mammography screening. With neoadjuvant chemotherapy was achieved complete pathological remission in 15% patients, in 70% patients reduction volume of the tumor at least 50%, other patients were resistant to chemotherapy. Recurrence of disease was detected by almost 39% of patients on condition follow-up at least 30 months after completion of primary treatment. Patients, who were diagnosed and treated in early stages, suffered more frequently from local recurrence and interval of recurrence from completion of primary treatment was longer. Patients, who were diagnosed and treated in advanced stages, suffered more frequently from remote metastasis and interval of recurrence from completion primary treatment was shorter., Conclusion: Triple negative cancers of breast are highly aggressive tumors with poor prognosis. They often are associated with lymphadenopathy and characterized by frequent occurrence of local recurrences and high risk of remote metastases. These tumors represent a large part of so-called interval cancers. Tumors often occurs in young women with BRCA1 mutations. Elementary systemic treatment is chemotherapy. Together continues the effort of highly targeted therapy, based on new findings in genomics and proteomics and on detection of many markers expressed by this version of breast cancer.

Objective: Information sheet about metastatic tumors of the female genital tract., Design: Literature review with case reports., Setting: Department of Gynaecology and Obstetrics, Faculty of Medicine, Masaryk's University and Fakulty Hospital, Brno., Methods: Literature review about metastatic tumors of the female genital tract with illustrative case reports., Conclusions: Secondary gynecological malignant tumors are much less common than primary tumors of the female genital tract with the exception cancer of the fallopian tube and the vagina. Primary malignant tumors of the fallopian tube and the vagina are rare, the primary location of the tumor usually is in other areas of the female genital tract and the tumor grows directly into the above-mentioned organs secondarily. There is talking about metastatic malignant tumors of the female genital tract in the strict sense in the case of extragenital primary origin the cancer. Metastases can be caused by direct penetration of the tumor from anatomically adjacent organs, particularly from the bladder and the rectum, or are going through the lymph or the blood vessels. The most common primary location of the tumor are the breast, the stomach and the bowel in this case. Secondary laesions of the female genital tract can be sometimes the first clinical manifestation of the primary extragenital malignant tumor, simultaneously represent clearly negative prognostic factor for the disease. Differential diagnostic algorithm for solving the secondary laesions of the female genital tract requires a multidisciplinary approach and cooperation with the pathologist and the clinical oncologist. Surgical treatment, the indication and extent based on adequately performed staging, is essential for the diagnosis of the primary tumor and is necessary as the palliative treatment for the elimination event, clinical symptoms and for the improving quality of the life.

Two cases of malignant fibrous histiocytoma (MFH) of the breast are presented. The first case was a 63-year-old patient with MFH of myxoid type, the second case was a 79-year-old patient with MFH of pleiomorphic type. MFH is one of the most common tumors of the soft tissues, but its primary occurrence in the breast is rare. Immunohistochemical detection of antigens in the cytoplasm of histiocytes by antibdy LN 5 (Anti-Macrophage, BioGenex) can be helpful in rendering of the right diagnosis.

p53 status is an important predictive factor in breast cancer, but the results of many studies are ambiguous. We tested p53 by functional analysis of separated alleles in yeast (FASAY) as well as by immunohistochemistry (IHC) and evaluated correlations with main prognostic factors, proliferation, and Bcl-2. Thirty-two tumors were tested with antibodies BP53-12, DO1, DO11, DO12, and by FASAY. Spearman rank correlations were tested separately with age, tumor type, pT, grade, pN, NPI, Ki-67, S-phase, proliferation index, Bcl-2, and steroid receptor status determined by ER, PR, and pS2. FASAY showed significant correlations with ductal type, grade and proliferation, and an inverse correlation with functional estrogen receptor and Bcl-2. FASAY provided better correlations compared to p53 IHC. We conclude that FASAY shows significant correlations with main prognostic/predictive factors and provides more reliable biological information compared to p53 IHC. Apoptosis is positively linked to proliferation and is not under the control of p53, which is frequently mutated in highly proliferating carcinomas. FASAY seems to be very important in assessing the predictive significance of p53 for a specific therapy of breast cancer.

Mutations and diminished expression of the E-cadherin gene (CDH1) have been identified in a number of epithelial malignancies. Although somatic CDH1 mutations were detected in lobular breast cancer with a frequency ranging from 10-56%, CDH1 alterations in more frequent ductal tumors appear to be rare. Here we have analyzed the coding region of CDH1 for mutations using denaturing high performance liquid chromatography and found 4 mutations in 83 ductal carcinomas (5%) and 3 mutations in 25 lobular carcinomas (12%). The germline of 13 patients with familial lobular tumors was also analyzed for mutations, but none were detected. In a case-control study, we also tested whether a variant adenine allele in the promoter polymorphism -161C-->A with a putative influence on the transcriptional activity of CDH1 in vitro confers any detectable risk of breast cancer. No significant difference in the allelic frequency between patients with breast cancer (326/1,152, 28.3%) and controls (190/696, 27.3%, p > 0.05; relative risk 1.05, 95% confidence interval 0.85-1.30) was found. A novel promoter polymorphism was identified at position -152, but the frequency of the variant cytosine allele was also similar in patients with breast cancer and controls (0.71% vs. 0.21%, p = 0.23). Transient transfection experiments using reporter constructs containing the nucleotide substitutions -161C/-152C and -161A/-152T showed only a slight decrease in the transcription activity compared to the wild-type construct. These results do not support CDH1 as a prominent low-penetrance cancer susceptibility gene, but indicate that CDH1 mutations contribute to the progression of both lobular and ductal tumors., (Copyright 2001 Wiley‐Liss, Inc.)

Leptin is a nonglycosylated protein produced mostly by adipocytes. The role ofleptin in body weight regulation through its anorectic effect in hypothalamus is very well known. Less known are other leptin effects such as the stimulation of hematopoesis and some parts of immunity system. The role of leptin in the pathogenesis of some malignant tumors is discussed. Only a little is known about bone marrow adipocyte leptin production. We examined leptin concentrations in the sera from peripheral blood and bone marrow, the percentage of bone marrow fat, the degree of bone marrow infiltration, the body mass index (BMI) in 42 patients with lymphoproliferative diseases. We found that bone marrow has significantly lower leptin levels (6,6+/-10,9 ng/ml) than peripheral blood (9,1+/-11,5 ng/ml) (p < 0.0001). Bone marrow and peripheral blood leptin levels have also a significant thin correlation (r = +0.91, p < 0.0001). Bone marrow (r = +0.55, p < 0.0005) and peripheral blood (r = +0.52, p < 0.0005) leptin concentrations are significantly correlated to BMI. Blood serum leptin (r = +0.46, p < 0.003) and bone marrow leptin (r = +0.40, p < 0.01) are related to the bone marrow fat percentage. In addition we found a negative correlation of blood serum leptin (r = -0.59, p < 0.0001) and bone marrow leptin (r = -0.42, p < 0.005) to bone marrow malignant infiltration. When we divided the patients into groups with bone marrow infiltration more than 10% and without or less than 10% infiltration, the first group had significantly lower peripheral blood (p < 0.001) and bone marrow (p < 0.02) leptin. We also confirmed a relation of bone marrow fat and infiltration (r = +0.49, p < 0.001). Our results suggest a relationship among leptin levels in blood or bone marrow and bone marrow infiltration in lymphoproliferative diseases. This fact needs further investigation and an evaluation of its application in clinical practice.

The prognostic and predictive value of p53 mutation in breast cancer is still conflicting. The choice of the p53 status detection method may account for some discrepancies. In this pilot study we compared two differently-based methods for detection of p53 alteration in 32 breast carcinoma samples: the immunohistochemical method using Bp53, DO1 and DO11 monoclonal antibodies for analysis of the p53 protein accumulation in cell nuclei and the functional method FASAY. FASAY - functional analysis of the separated alleles in yeast - tests the capability of the human p53 to transactivate a reporter with a p53 binding site RGC driving the ADE2 gene in yeast. In our group the percentage of breast cancers with accumulated p53 protein was 50%, as well as percentage of mutant p53 scored by FASAY was 50%. Although the agreement of both methods, when comparing the results of individual patients was high (94%), our results show that immunohistochemistry does not reflect the p53 status quite exactly.