Differential microRNA Expression Analysis in Patients with HPV-Infected Ovarian Neoplasms.

This study aimed to identify microRNAs (miRNAs) whose expression levels are altered by high-risk human papillomavirus (HR-HPV) infection in women with epithelial ovarian neoplasms. MiRNA expression was quantified by real-time polymerase chain reaction, while HR-HPV DNA was quantified using digital-droplet PCR. Analysis of 11 miRNAs demonstrated significantly lower hsa-miR-25-5p expression in HPV-infected compared to uninfected ovarian tissues (p = 0.0405), while differences in miRNA expression in corresponding serum were statistically insignificant. The expression of hsa-miR-218-5p in ovarian tumors was significantly higher in high-grade serous ovarian carcinoma (HGSOC) cases than in other neoplasms (p = 0.0166). In addition, hsa-miR-218-5p was significantly upregulated, whereas hsa-miR-191-5p was significantly downregulated in tissues with stage III/IV FIGO (p = 0.0009 and p = 0.0305, respectively). Using unsupervised clustering, we identified three unique patient groups with significantly varied frequencies of HPV16/18-positive samples and varied miRNA expression profiles. In multivariate analysis, high expression of hsa-miR-16-5p was an independent prognostic factor for poor overall survival (p = 0.0068). This preliminary analysis showed the changes in miRNA expression in ovarian neoplasms during HPV infection and those collected from HGSOCs or patients with advanced disease. This prospective study can provide new insights into the pathogenesis of ovarian neoplasms and host-virus interactions.

miRNA Expression Profiles in Ovarian Endometriosis and Two Types of Ovarian Cancer-Endometriosis-Associated Ovarian Cancer and High-Grade Ovarian Cancer.

Endometriosis-associated ovarian cancer (EOC) consisting of endometrioid cancer and clear-cell ovarian cancer could be promoted by many factors. miRNAs, which are small, non-coding molecules of RNA, are among them. The aim of this study was to detect miRNAs connected with the malignant transformation of endometriosis. FFPE (formalin-fixed, paraffin-embedded) samples of 135 patients operated on for endometriosis and different types of ovarian cancer (EOC and HGSOC-high-grade serous ovarian cancer) were studied. Healthy ovarian tissue was used as a control group. From the expression panel of 754 miRNAs, 7 were chosen for further tests according to their ROC (receiver operating characteristic) curves: miR-1-3p, miR-125b-1-3p, miR-31-3p, miR-200b-3p, miR-502-5p, miR-503-5p and miR-548d-5p. Furthermore, other potentially important clinical data were analysed, which included age, BMI, Ca-125 concentration, miscarriages and deliveries and concomitant diseases such as hypertension, type 2 diabetes and smoking. Among the miRNAs, miR200b-3p had the lowest expression in neoplastic tissues. miR31-3p had the highest expression in women without any lesions in the ovaries. miR-502-5p and miR-548-5p did not differ between the studied groups. The examined miRNA panel generally distinguished significantly normal ovarian tissue and endometriosis, normal ovarian tissue and cancer, and endometriosis and cancer. The malignant transformation of endometriosis is dependent on different factors. miRNA changes are among them. The studied miRNA panel described well the differences between endometriosis and EOC but had no potential to differentiate types of ovarian cancer according to their origin. Therefore, examination of a broader miRNA panel is needed and might prove itself advantageous in clinical practice.

How to Improve Non-Invasive Diagnosis of Endometriosis with Advanced Statistical Methods.

Background and Objectives: Endometriosis is one of the most common gynecological disorders in women of reproductive age. Causing pelvic pain and infertility, it is considered one of the most serious health problems, being responsible for work absences or productivity loss. Its diagnosis is often delayed because of the need for an invasive laparoscopic approach. Despite years of studies, no single marker for endometriosis has been discovered. The aim of this research was to find an algorithm based on symptoms and laboratory tests that could diagnose endometriosis in a non-invasive way. Materials and Methods: The research group consisted of 101 women hospitalized for diagnostic laparoscopy, among which 71 had confirmed endometriosis. Data on reproductive history were collected in detail. CA125 (cancer antigen-125) level and VEGF1(vascular endothelial growth factor 1) were tested in blood samples. Among the used statistical methods, the LASSO regression-a new important statistical tool eliminating the least useful features-was the only method to have significant results. Results: Out of 19 features based on results of LASSO, 7 variables were chosen: body mass index, age of menarche, cycle length, painful periods, information about using contraception, CA125, and VEGF1. After multivariate logistic regression with a backward strategy, the three most significant features were evaluated. The strongest impact on endometriosis prediction had information about painful periods, CA125 over 15 u/mL, and the lowest BMI, with a sensitivity of 0.8800 and a specificity of 0.8000, respectively. Conclusions: Advanced statistical methods are crucial when creating non-invasive tests for endometriosis. An algorithm based on three easy features, including painful menses, BMI level, and CA125 concentration could have an important place in the non-invasive diagnosis of endometriosis. If confirmed in a prospective study, implementing such an algorithm in populations with a high risk of endometriosis will allow us to cover patients suspected of endometriosis with proper treatment.

Cancer Stem Cells in Ovarian Cancer-A Source of Tumor Success and a Challenging Target for Novel Therapies.

Ovarian cancer is the most lethal neoplasm of the female genital organs. Despite indisputable progress in the treatment of ovarian cancer, the problems of chemo-resistance and recurrent disease are the main obstacles for successful therapy. One of the main reasons for this is the presence of a specific cell population of cancer stem cells. The aim of this review is to show the most contemporary knowledge concerning the biology of ovarian cancer stem cells (OCSCs) and their impact on chemo-resistance and prognosis in ovarian cancer patients, as well as to present the treatment options targeted exclusively on the OCSCs. The review presents data concerning the role of cancer stem cells in general and then concentrates on OCSCs. The surface and intracellular OCSCs markers and their meaning both for cancer biology and clinical prognosis, signaling pathways specifically activated in OCSCs, the genetic and epigenetic regulation of OCSCs function including the recent studies on the non-coding RNA regulation, cooperation between OCSCs and the tumor microenvironment (ovarian cancer niche) including very specific environment such as ascites fluid, the role of shear stress, autophagy and metabolic changes for the function of OCSCs, and finally mechanisms of OCSCs escape from immune surveillance, are described and discussed extensively. The possibilities of anti-OCSCs therapy both in experimental settings and in clinical trials are presented, including the recent II phase clinical trials and immunotherapy. OCSCs are a unique population of cancer cells showing a great plasticity, self-renewal potential and resistance against anti-cancer treatment. They are responsible for the progression and recurrence of the tumor. Several completed and ongoing clinical trials have tested different anti-OCSCs drugs which, however, have shown unsatisfactory efficacy in most cases. We propose a novel approach to ovarian cancer diagnosis and therapy.

Human Papillomaviruses as Infectious Agents in Gynecological Cancers. Oncogenic Properties of Viral Proteins.

Human papillomaviruses (HPVs), which belong to the Papillomaviridae family, constitute a group of small nonenveloped double-stranded DNA viruses. HPV has a small genome that only encodes a few proteins, and it is also responsible for 5% of all human cancers, including cervical, vaginal, vulvar, penile, anal, and oropharyngeal cancers. HPV types may be classified as high- and low-risk genotypes (HR-HPVs and LR-HPVs, respectively) according to their oncogenic potential. HR-HPV 16 and 18 are the most common types worldwide and are the primary types that are responsible for most HPV-related cancers. The activity of the viral E6 and E7 oncoproteins, which interfere with critical cell cycle points such as suppressive tumor protein p53 (p53) and retinoblastoma protein (pRB), is the major contributor to HPV-induced neoplastic initiation and progression of carcinogenesis. In addition, the E5 protein might also play a significant role in tumorigenesis. The role of HPV in the pathogenesis of gynecological cancers is still not fully understood, which indicates a wide spectrum of potential research areas. This review focuses on HPV biology, the distribution of HPVs in gynecological cancers, the properties of viral oncoproteins, and the molecular mechanisms of carcinogenesis.

ERAP/HLA-C and KIR Genetic Profile in Couples with Recurrent Implantation Failure.

Proper embryo implantation depends on the tolerance of the maternal immune system to the fetus and its foreign paternal antigens. During implantation and early pregnancy, the dominant leukocytes in the uterus are uterine NK cells, expressing killer immunoglobulin-like receptors (KIR). KIRs recognize human leukocyte antigens (HLA-C) on the human trophoblast inherited from the father and mother. The antigenic peptides presented by the HLA are formed via their cleavage by endoplasmic reticulum aminopeptidases ERAP1 and ERAP2. The aim of this study was to assess the association of combined KIR genes and their HLA-C ligands, as well as ERAP1 and ERAP2 polymorphisms with recurrent implantation failure after in vitro fertilization (RIF). We tested 491 couples who underwent in vitro fertilization (IVF) and 322 fertile couples. Genotype CC rs27044 ERAP1 in female with a male's HLA-C1C1 or HLA-C1C2 protected from RIF (p/pcorr. = 0.005/0.044, OR = 0.343; p/pcorr. = 0.003/0.027, OR = 0.442, respectively). Genotype TT rs30187 ERAP1 in female with a male's HLA-C1C2 genotype increased the risk of RIF. Summarizing, in the combination of female ERAP1 and an HLA-C partner, the rs30187 C>T and rs27044 C>G polymorphisms play an important role in implantation failure.

miR 31-3p Has the Highest Expression in Cesarean Scar Endometriosis.

Micro-RNAs expression can vary between different forms of endometriosis, but data on miRNA expression in cesarean scar endometriosis is lacking. The present study is comprised of 30 patients with endometriosis in the cesarean scar (scar endometriosis, SE), 14 patients with deep infiltrating endometriosis (DIE), 47 patients with endometrioma (ovarian endometrial cyst, OE), and 33 patients with healthy ovarian tissue as the control group (CG). In the initial experiment to identify possible dysregulated miRNAs, the levels of 754 miRNAs in formalin-fixed paraffin-embedded tissue (FFPE) samples from OE, high-grade ovarian cancer, endometrioid ovarian cancer, and CG were measured. We identified seven potentially dysregulated miRNAs: miR-1-3p, miR-31-3p, miR-125b-1-3p, miR-200b-3p, miR-548d, miR-502, and miR-503. We then examined the expression profiles of each of these miRNAs individually in the SE, DIE, OE, and CG FFPE samples using RT-qPCR. miR-31-3p had significantly higher levels of expression and miR-125b-1-3p had significantly lower levels of expression in SE compared to the controls. Overall, the higher expression levels of miR-31-3p and the lower expression levels of miR-125b-1-3p are consistent with the benign nature of SE. Importantly, the results of the present study demonstrate the possibility of using miRNA to monitor the risk of malignant transformation of endometriosis tissue.

KIR and HLA-C genes in male infertility.

PURPOSE: Approximately 50% of men reporting to clinics for assisted reproduction have abnormal sperm parameters; we therefore considered whether they differ from fertile males in terms of the frequency of KIR and HLA-C genes, suggesting the involvement of NK cells and some T cells in the inflammatory reaction that can occur in the testes, vas deferens, or epididymis. METHOD: We tested a total of 1064 men: 445 of them were patients who, together with their female partners, participated in in vitro fertilization (IVF), 298 men whose female partners suffered from recurrent spontaneous abortion. Three hundred twenty-one fertile men constituted the control group. KIRs were genotyped using KIR Ready Gene kits and HLA-C by PCR-SSP methods. RESULTS: We found differences in KIR gene frequencies between men who became fathers via natural conception and men who participated in in vitro fertilization for KIR2DL2 (p/pcorr. = 0.0015/0.035, OR = 1.61), KIR2DL5 gr.2 (p/pcorr. = 0.0023/0.05, OR = 1.64), KIR2DS2 (p/pcorr. = 0.0019/0.044, OR = 1.59), and KIR2DS3 (p/pcorr. = 0.0016/0.037, OR = 1.67). KIRs in Cen AA region were significantly overrepresented in fertile males than in IVF males (p/pcorr. = 0.0076/0.03, OR = 0.67), whereas Cen AB + Cen BB frequency was higher in IVF males than in fertile males (p/pcorr. = 0.0076/0.03, OR = 1.50). We also observed a limited association in KIR-HLA-C combinations. CONCLUSION: Fertile men differ in profile of KIR genes and KIR-HLA-C combinations from men participating in IVF.

The impact of HLA-G, LILRB1 and LILRB2 gene polymorphisms on susceptibility to and severity of endometriosis.

Endometriosis is a disease in which endometriotic tissue occurs outside the uterus. Its pathogenesis is still unknown. The most widespread hypothesis claims that ectopic endometrium appears as a result of retrograde menstruation and its insufficient elimination by immunocytes. Some reports have shown expression of non-classical HLA-G molecules on ectopic endometrium. HLA-G is recognized by KIR2DL4, LILRB1 and LILRB2 receptors on natural killer (NK) and other cells. These receptors are polymorphic, which may affect their activity. In this study we investigated whether HLA-G, KIR2DL4, LILRB1 and LILRB2 polymorphisms may influence susceptibility to endometriosis and disease progression. We used polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP) and allelic discrimination methods with TaqMan SNP Genotyping Assays for typing of 276 patients with endometriosis and 314 healthy fertile women. The HLA-G rs1632947:GG genotype was associated with protection against the disease and its severe stages; HLA-G rs1233334:CT protected against progression; LILRB1 rs41308748:AA and LILRB2 rs383369:AG predisposed to the disease and its progression. No effect of KIR2DL4 polymorphism was observed. These results support the role of polymorphisms of HLA-G and its receptors LILRB1 and LILRB2 in susceptibility to endometriosis and its progression.

Clinical significance of miRNA-21, -103, -129, -150 in serous ovarian cancer.

PURPOSE: We aimed to compare expression levels of miRNA-21, -103, -129, -150 in primary tumour tissues and its omental metastases from patients operated for advanced ovarian serous cancer. Expression levels of selected miRNAs were correlated with clinicopathological features, including chemosensitivity and survival. METHODS: We performed total RNA extraction from archival formalin-fixed paraffin-embedded tissue samples of primary serous ovarian cancer and omental metastases. The study included 48 patients with advanced ovarian cancer. The reference group consisted of 48 normal ovarian tissue samples. We performed cDNA synthesis, real time polymerase chain reaction and assessed relative expression of selected miRNAs. RESULTS: Samples derived from serous ovarian cancer were characterized by higher expression levels of miRNA-150 in comparison to omental metastases (p = 0.045). Furthermore, we observed that shorter progression free-survival was associated with lower levels of miRNA-150 in metastatic tissues. We did not find similar relationships for other miRNAs. CONCLUSIONS: MiRNA-150 may potentially serve as a prognostic factor in advanced ovarian cancer. However, further studies are required to clearly confirm such hypothesis.

[Cerebroplacental ratio (CPR) and amniotic fluid index (AFI) as prognostic factors of terminating pregnancy with cesarean section after induction of labour]. / Wskaznik mózgowo-pepowinowy i indeks plynu owodniowego jako czynniki prognostyczne zakonczenia indukcji porodu cieciem cesarskim w ciazach po skonczonym 41 tygodniu.

AIM: The aim of the study was to estimate the value of the cerebroplacental ratio (CPR) and amniotic fluid index (AFI) in pregnancies after 41 week as prognostic factors of terminating pregnancy with cesarean section after induction of labour. MATERIALS AND METHODS: The study included 130 pregnant women, including 100 women, between 41 and 42 weeks of gestation, in whom induced labour resulted in a cesarean section due to three main indications: lack of progress of labour - group I - 44 pregnant women, signs of foetal distress - group II - 32 pregnant women and lack of response to induced labour - group III - 24 pregnant women. The control group (group IV) included 30 pregnant women between 41 and 42 completed weeks of gestation, in whom induction resulted in a physiological labour. CPR and AFI were analysed. The procedures were conducted with the use of Medison SA 9900 vaginal and abdominal probes. RESULTS: It was observed statistically significant difference beetween the studied and control groups with CPR (1.51+/-0.54 vs. 1.88+/-0.67 p<0,05). The lowest values of CPR were observed in Group II (1.18+/ -0.39). The AFI variable (5.93+/-3.19 p<0,05) was significantly lower in comparison to the other groups (I-10.27+/-4.3 p<0,05, III-9.24+/- 2.85 p<0,05, IV-9.43+/-3.46 p<0,05). There was a positive significant correlation between AFI and CPR (r=0.661; p=0.000 and r=0.610; p=0.000) in the group II. CONCLUSIONS: The values of CPR and AFI in pregnancies after 41 week could be prognostic factors of terminating pregnancy with cesarean section after induction of labour. An application of integrated model of evaluation of a foetus condition after 41 week of gestation (CPR, AFI and CTG) might allow to avoid making early decisions on performing labour induction, and thus, reduce the number of hastily conducted cesarean sections due to lack of response to oxytocin or due to lack of progress of labour.

[Assessment of relationship between Doppler flows in pregnancies after 41 week and the incidence of cesarean sections with induced labour]. / Wartosc prognostyczna przeplywów dopplerowskich po 41 tygodniu ciazy w przewidywaniu zakonczenia indukcji porodu cieciem cesarskim.

AIM: The aim of the study was to assess a relationship between the Doppler flows in foetal vessels, i.e. the middle cerebral artery (MCA), umbilical artery (UMA), umbilical vein (UV) and ductus venosus (DV) as well as in maternal vessels, i.e. the right uterine artery (UAR), left uterine artery (UAL) and the incidence of cesarean sections in pregnancies after 41 week with induced labour. MATERIALS AND METHODS: The study included 130 pregnant women, including 100 pregnant women, between 41 and 42 weeks of gestation, in whom induced labour resulted in a cesarean section due to three main indications: lack of progress of labour (Group I-44), signs of foetal distress (Group II-32) and lack of response to induced labour (Group III-24). The control group (Group IV) included 30 pregnant women between 41 and 42 completed weeks of gestation, in whom induction resulted in a physiological labour. Vascular flow was analysed in vessels, foetal, i.e. MCA, UMA, UV, DV and maternal, i.e. UAR, UAL. The procedures were conducted with the use of Medison SA 9900 vaginal and abdominal probes. RESULTS: There are observed statistically significant differences between the studied and control groups with regards to values of the variables: PSV MCA (58.64 +/-13.72 vs. 52.73 +/-10.9 p<0,05), S/D UMA (2.61 +/-1.16 vs. 2.06 +/-0.45 p<0,05), PI UMA (0.84 +/-0.23 vs. 0.7 +/-0.19 p<0,05), RI UMA (0.58 +/-0.13 vs. 0.5 +/-0.11 p<0,05). In Group II values of pulsatility index (PI) both uterine arteries are statistically significant higher (0,83 +/-0,29) than in other groups (I: 0,6 +/-0,19 p<0,05, III: . 0,61 +/-0,15 p<0,05, IV 0,64 +/-0,17 p<0,05). CONCLUSIONS: Assessment of Doppler flows in pregnancies after 41 week might allow to select pregnant women who are at a greater risk of terminating pregnancy with cesarean section after induction of labour.

Women's fertility after laparoscopic cystectomy of endometrioma and other benign ovarian tumors - a 24-month follow-up retrospective study.

OBJECTIVES: The golden standard in treatment benign ovarian cysts is laparoscopic cystectomy, but it may also influence women's fertility. The aim of the study was to compare women's fertility after laparoscopic cystectomy of endometrioma versus other benign ovarian tumors. MATERIALS AND METHODS: Out of the 123 patients operated because of benign ovarian tumor (OT), 66 underwent laparoscopic cystectomy of endometrioma (endometrioma group) and 57 underwent laparoscopic cystectomy of other benign ovarian tumor like: functional cyst, hemorrhagic cyst, yellow body cyst or mature teratoma (reference group). OT-related data were obtained from medical documentation (diagnostic tests, medical reproductive and surgical history, clinical status during OT surgery). Follow-up data were collected by means of a telephone interview. The survey included questions focused on women's fertility during a 24-month period following the surgical treatment of OT (conception, subsequent pregnancies, recurrence of OT). RESULTS: A 24-month follow-up period revealed that the cumulative pregnancy rate was significantly higher in reference group (RG) as compared to endometrioma group (EG), i.e. 52.6% vs. 32.3%. Lower pregnancy risk was demonstrated in a EG group vs. other benign ovarian tumors, HR=0.57 (CI 0.33-0.99; p=0.049), log-rank test p=0.045. Benign OT returned in 19.3% vs. EG 36.3%, HR= 2.5 (CI 1.16-5.55 ; p=0.019) log-rank test: p=0.0136. The EG was divided on two subgroups: women with solitary endometrioma and women with endometrioma and coexistent peritoneal endometriosis. The study showed insignificantly lower risk of pregnancy in a group of advanced endometriosis vs. solitary endometrioma group (HR= 0.79 (CI 0.34-1.83; log-rank test p=0.57; pregnancy rate 29.3% vs. 40.0%). Statistically nonsignificant higher pregnancy rate occurred in a group of women with tumor ≤50mm in size among patients with benign ovarian tumor and solitary endometrioma vs. group of women with tumor >50mm (30% vs. 61%; p=0.09). CONCLUSIONS: There is a low pregnancy rate after laparoscopic cystectomy of benign OT. Moreover, pregnancy rate after cystectomy of endometrioma is significantly lower and the percentage of reccurence of endometrioma is significantly higher. That is why, the decision about surgical treatment among childbearing women must be well-considered because of the risk of subsequent surgery in the future.

The significance of markers in the diagnosis of endometrial cancer.

Endometrial cancer is one of the most common cancers experienced by women throughout the world. It is also the most common malignancy within the female reproductive system, representing 37.7% of all disorders. The incidence increases with age, and is diagnosed most frequently in women between 45 and 65 years old. In the last few years, numerous studies have been performed to identify tumour biomarkers. Biomarkers include not only protein routinely used as tumour markers but also genes and chromosomes. The limiting factor in the use of markers in the diagnosis of endometrial cancer is their lack of specificity. However, specific markers for endometrial cancer are the subject of much research attention. Although moderately elevated levels of markers are present in a number of inflammatory or non-malignant diseases, significantly increased levels of markers indicate the development of cancer. Recently, research has been focused on the identification of molecular changes leading to different histological subtypes of endometrial cancer. In this paper the authors reviewed several currently investigated markers. Progress in these investigations is very important in the diagnostics and treatment of endometrial cancer. In particular, the identification of novel mutations and molecular profiles should enhance our ability to personalise adjuvant treatment with genome-guided targeted therapy.

Leiomyomatosis peritonealis disseminata of unusual course with malignant transformation: case report.

Leiomyomatosis peritonealis disseminata is a very rare, benign entity of unknown pathogenesis, characterized by the presence of multiple subperitoneal or peritoneal smooth muscle nodules throughout the peritoneal surface. Mostly the course is asymptomatic and it is found incidentally during laparotomy, laparoscopy or cesarean section. Non-specific symptoms such as abdominal pain, vaginal bleeding, abdominal mass or gastrointestinal signs are described. Rare cases of malignant transformation have been reported. We present a case of disseminated peritoneal leiomyomatosis with an unusual course and transformation to endometrial sarcoma in a 26-year-old previously healthy woman, where the appearance of peritoneal nodules was preceded by multiple incidents of fast fibroid growth and delivery of myomatous growth into the cervical canal.

[(Un)Forgotten Neugebauer-Le Fort operation. Paramedian closure of the vagina--safe and effective surgical procedure for treating of pelvic organ prolapse in older women]. / (Nie) Zapomniana operacja Neugebauera-Le Forta. Posrodkowe zamkniecie pochwy-bezpieczna i skuteczna procedurar zabiegowego leczenia wypadania narzadu plciowego u starszych kobiet.

OBJECTIVES: The aim of the study is to present data concerning Neugebauer-Le Fort operations performed at the Gynecologic Oncology Clinic, Polish Mother's Health Center Research Institute in Lodz between 2000-2009, including the effects of the surgeries on improving quality of life. MATERIAL AND METHODS: Our research included all patients (90 women) operated due to total pelvic organ prolapse (stage IV of POP-Q) in Gynecologic Oncology Clinic. The data was collected retrospectively from medical records. Results of the treatment were evaluated based upon surveys and control checkups. The p-value of 0.05 was considered statistically significant. RESULTS: Mean patient age was 76.5 years. The analysis of medical records showed that 35% of the subjects had a BMI index >30. Out of 90 patients, 53%, 30% and 4% of the women had 2, 3, and 4 natural deliveries, respectively whereas 16% had forceps delivery Of the 65 operated patients, in more than 92% all the symptoms connected with pelvic organ prolapse disappeared. Problems with the urinary tract (urinary incontinence 'de novo', urinary tract infections) emerged in 13% and constipation in 5% of the women. As far as improved quality of life after the surgery is concerned, 93% of the subjects answered 4 and 5 (in a scale from 1 to 5). CONCLUSIONS: Neugebauer-Le Fort surgery is characterized by high effectiveness both, in objective research and subjective ratings of the operated patients. A high safety profile constitutes a great advantage of the surgery as was confirmed in our study In carefully selected group of patients with stage IV of POP-Q, Neugebauer-Le Fort surgery is a safe and effective procedure.

[Evaluation of applicability of HE4 and ROMA in the preoperative diagnosis of adnexal masses]. / Ocena uzytecznosci oznaczen bialka HE4 i algorytmnu ROMA w przedoperacyjnej diagnostyce guzow przydatków.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of HE4 alone and in combination with CA 125 (ROMA) in selecting patients at high risk of adnexal malignancy. MATERIAL AND METHODS: Serum CA 125 and HE4 levels were determined and the ROMA value was calculated in 259 women qualified for surgery due to adnexal mass. The results were compared with histopathological findings. RESULTS: Sensitivity and specificity in preoperative diagnosis of primary ovarian cancer were 93.2% and 71.5% for CA 125 and 95.4% and 81.3% for HE4, respectively ROMA algorithm achieved sensitivity of 95.4% and specificity of 79.8%. All methods reached sensitivity of 100% at specificity of 65.6% for CA125, 93.4% for HE4 and 82.0% for ROMA in premenopausal women, whereas in postmenopausal women sensitivity and specificity achieved levels of 92.1% and 81.7% for CA 125, 94.7% and 60.6% for HE4 and 94.7% and 76.1% for ROMA, respectively Serum levels of both CA 125 and HE4 were significantly higher in women with primary ovarian cancer as compared to benign disease. Concentrations of CA 125 in patients with endometriosis were significantly elevated as compared to women with other benign tumors. Such relation was not observed when HE4 levels were concerned. CONCLUSIONS: CA 125, HE4 and ROMA are useful in preoperative diagnosis of ovarian malignancy HE4 improves the diagnostic accuracy in cases of endometriosis, verifying false positive results of CA 125.

Current clinical application of serum biomarkers to detect ovarian cancer.

For the last decades, hundreds of potential serum biomarkers have been assessed in diagnosing of ovarian cancer including the wide spectrum of cytokines, growth factors, adhesion molecules, proteases, hormones, coagulation factors, acute phase reactants, and apoptosis factors but except CA125 none of them have been applied to everyday clinical practice. Nowadays, the growing number of evidence suggests that the classic marker CA125 should be accompanied by HE4 and in fact, Risk of Ovarian Malignancy Algorithm (ROMA) is becoming more and more widespread in clinical practice for the evaluation of adnexal masses. Early ovarian cancer is often asymptomatic, so the challenge still exists to develop serum markers suitable for early diagnosis and screening. Current knowledge strongly points to different mechanisms of pathogenesis, genetic disturbances and clinical course of major histological subtypes of ovarian cancer. Thus, future biomarker/multimarker panels should take into consideration the implications of different molecular patterns and biological behavior of various subtypes of ovarian cancer. Very promising are studies on miRNAs - small non-protein coding gene-regulatory RNA molecules functionally involved in the pathogenesis of cancers acting as oncogenes (oncomirs) or tumor suppressors. The studies devoted to ovarian cancer tissue miRNA profiling have shown that miRNAs could be useful in diagnosing and predicting the OC outcome. They also confirmed that OC is a highly heterogeneous disease, gathering four distinct histological tumor subtypes characterized not only by distinct origin, behavior and response to chemotherapy but also by different patterns of miRNA expression.

Microvesicles as a potential biomarker of neoplastic diseases and their role in development and progression of neoplasm.

Neoplastic diseases together with cardiovascular diseases are the most frequent causes of death in the Polish population. Cancers of reproductive organs with breast cancer are responsible for the highest morbidity and mortality in women suffering from neoplasm diseases. Asymptomatic dynamics of the development of a neoplasm and no deviations from the normal level of laboratory results contribute to the fact that malignant diseases are diagnosed too late. The aim of modern medicine is to diagnose cancer at the earliest stage, however, there is no sufficiently sensitive and specific biomarker which can be used for diagnostic, prognostic and therapeutic purposes. Cellular interactions play the main role in the development, angiogenesis and invasiveness of a tumor. Recent research suggests the possibility of microvesicles (MVs) involvement in communication between cells. The MVs ability to fuse with various cells is used in cell-to-cell contact. Microvesicles cargo may include growth factors, their receptors, protease, adhesion molecules, signaling molecules and the sequence of DNA, mRNA, and micro-RNA. Larger quantities of MVs released from neoplastic cells affect both the local environment and systematic range causing metastases and progression. The research on molecular mechanisms of MVs' release and the presence of characteristic oncogenes in blood of patients with neoplasms is being carried out. Confirmation of MVs presence in patients' serum can potentially serve as useful information for therapeutic purposes and as the biomarker of a neoplastic disease.

Hemostatic disorders of the menopausal period: the role of microRNA.

Adverse changes in hemostasis of menopausal women, observed e.g. in atherosclerotic or neoplastic cases, are of multicausal origin. It is believed that in the development and regulation of these processes, an important role is played by microRNA particles, which presence is ascertained in endothelial cells, atherosclerotic plaques and systemic circulation. Discovered for the first time over 20 years ago, up to now over two and a half thousand types of microRNA have been identified in the human body. MicroRNAs are single stranded RNA molecules of 20-24 nucleotides, encoded by the cell's genome and then transcribed by polymerase II. They regulate the expression of a large gene pool, approximately 30% of all genes, in the human body. MicroRNA molecules, like other bioactive molecules - RNA, protein - both play important roles in tumor invasion, metastasis, inflammation, coagulation, and regeneration. What is important, they can be detected not only in tissues (e.g. tumor tissues), but also in circulation (blood serum), where they are released. Accurate understanding of the role played by certain types of microRNA (e.g. miR-126, miR-17-92, miR-33, miR-613, miR-27a/b, miR-143, miR-335, miR-370, miR-122, miR-19b, miR-520, or miR-220) in hemostatic processes may allow in the future for their use not only as specific biomarkers of cardiovascular diseases but also as the target for innovative gene therapies.