[Preoperative systemic treatment of locally and locoregionally advanced high-risk endometrial cancer]. / Lokálisan és lokoregionálisan elorehaladott, magas kockázatú endometriumtumorok mutét elotti szisztémás elokezelése.

Introduction: Endometrial cancer is the most common invasive gynecologic malignancy in developed countries. The best survival rates are expected after surgical removal, thus the aim of a complex treatment is to achieve resecability in locally and locoregionally advanced disease. Aim: The primary purpose of this study was to evaluate if the neoadjuvant systemic treatment leads to better overall survival compared to irradiation solely. Method: From January 2015 to December 2018, we enrolled 28 patients diagnosed with irresecable, locally and locoregionally advanced high-risk endometrial carcinoma. Patients were treated by neoadjuvant paclitaxel-carboplatin, then radical hysterectomy, bilateral oophorectomy and lymphadenectomy were performed. Results: After administration of 6 cycles of carboplatin-paclitaxel, the control MR test showed tumor shrinkage in all patients. Complete resection was achieved in the case of every patient. Tumor residuum in lymph nodes was verified in 4 cases by pathological evaluation. The 2-year survival and the 2-year progression-free survival rates were 65,1% and 66,1%, respectively. The median overall survival was 16,5 months. Conclusion: Neoadjuvant treatment can be an effective approach in providing the conditions for complete tumor resection, which may result in survival advantage. Despite multimodal treatment, prognosis is poor. Orv Hetil. 2020; 161(11): 425-433.

[Multimodal treatment of malignant mixed Müllerian tumor]. / Malignus kevert Müller-cso-eredetu tumor komplex kezelése.

INTRODUCTION AND AIM: The aim of our study was to evaluate the prognostic factors and treatment options of a very rare and highly aggressive type of uterine neoplasms, the malignant mixed Müllerian tumor, known as carcinosarcoma. METHOD: Between 2009 and 2017, 29 patients were treated with malignant mixed Müllerian tumor. At stage I, surgery and postoperative radiotherapy were performed. At stages II-IV, trimodal treatment (surgery, chemotherapy and radiotherapy) was administered. RESULTS: The average age of patients was 68.51 (49-90) years, mean body mass index was 30.22 (20.90-37.22). We have experienced recurrence of disease after complete resection in 6 cases (4 of 6 patients did not accept radiation therapy). Local recurrence has occurred after an average 15.52 (6-36) months, distant metastasis with an average 19.2 (8-32) months. Overall survival was 11.92 (1-75) months. Six patients are free of tumours at the moment. CONCLUSIONS: As overall survival has not increased in recent decades by using combined chemotherapy, there is no congruent consensus associated with the optimal treatment. The standard surgical treatment is total abdominal hysterectomy with bilateral oophorectomy, although due to high rates of recurrence and metastases, the necessity of lymphadenectomy and postoperative treatment is in the focus of recent studies. Though postoperative irradiation improves local control, the beneficial effect on overall survival is still not proven. Adjuvant chemotherapy decreases the rate of both pelvic and extrapelvic recurrence at the same time, although there is no recommendation for the optimal chemoterapeutic agent. Multimodal therapy should lead to better outcomes. Recently there are many ongoing studies with biologic and target therapies to improve efficiency, however, the relevant results will be disclosed in many years only, due to the small number of patients. Orv Hetil. 2018; 159(19): 741-7747.

Diagnostic relevance of urinary steroid profiles on ovarian granulosa cell tumors: two case reports.

BACKGROUND: Granulosa cell tumor of the ovary is the most frequent sex cord stromal tumor and represents 2 to 5% of all primary ovarian cancers. Ovarian granulosa cell tumor is a malignant tumor with slow progression and in some cases this tumor is hormonally active. The recurrence of granulosa cell tumor often happens after 5 years. CASE PRESENTATION: We describe two cases of postmenopausal women with adult-type granulosa cell tumors of the ovary. Patient 1 is a 49-year-old European woman with a recurrent tumor; patient 2 is a 55-year-old European woman without recurrence of tumor. Urinary steroid profiles of patient 1 were monitored during a 5-year period starting from before an operation (13 samples). In patient 2, the urinary steroid profiles were monitored during a 3-year period starting from after an operation (six samples). The 24-hour urinary samples were examined and the urinary concentration of 20 androgen, progesterone, and corticoid metabolites was quantitatively determined by gas chromatography-mass spectrometry with selected ion-monitoring mode. CONCLUSIONS: Based on these cases a correlation could be observed between increased levels of the urinary steroids and the recurrence of ovarian granulosa cell tumor; therefore, we concluded that a urinary steroid profile could be a more effective method to follow-up such patients compared to the traditional serum hormones determinations supplemented with conventional tumor markers.

A case study on the potential angiogenic effect of human chorionic gonadotropin hormone in rapid progression and spontaneous regression of metastatic renal cell carcinoma during pregnancy and after surgical abortion.

BACKGROUND: Treatment possibilities of metastatic renal cell carcinoma (mRCC) have recently changed dramatically prolonging the overall survival of the patients. This kind of development brings new challenges for the care of mRCC. CASE PRESENTATION: A 22 year-old female patient with translocation type mRCC, who previously had been treated for nearly 5 years, became pregnant during the treatment break period. Follow-up examinations revealed a dramatic clinical and radiological progression of mRCC in a few weeks therefore the pregnancy was terminated. A few days after surgical abortion, CT examination showed a significant spontaneous regression of the pulmonary metastases, and the volume of the largest manifestation decreased from ca. 30 to 3.5 cm(3) in a week. To understand the possible mechanism of this spectacular regression, estrogen, progesterone and luteinizing hormone receptors (ER, PGR and LHR, respectively) immuno-histochemistry assays were performed on the original surgery samples. Immuno-histochemistry showed negative ER, PGR and positive LHR status suggesting the possible angiogenic effect of human chorionic gonadotropin hormone (hCG) in the background. CONCLUSION: We hypothesize that pregnancy may play a causal role in the progression of mRCC via the excess amount of hCG, however, more data are necessary to validate the present notions and the predictive role of LHR overexpression.

MicroRNA expressions in HPV-induced cervical dysplasia and cancer.

BACKGROUND/AIM: The role of oncogenic or high-risk human papillomavirus (HPV) in cervical carcinogenesis is inevitable, yet not fully understood. Detailed analysis of microRNA (miRNA) alterations occurring during high-risk HPV transformation will increase our current understanding over cervical carcinogenesis. The two main aims of the study were: (i) finding association between HPV infection characteristics and socio-demographic variables, (ii) finding an predictors of clinical outcome. MATERIALS AND METHODS: The expression levels of different microRNAs (miR-21, miR-27a, miR-34a, miR-155, miR-196a, miR-203) were determined in formalin-fixed paraffin-embedded (FFPE) human HPV-positive cervical dysplastic and tumorous tissue samples using quantitative real-time PCR (qPCR). Sociodemographic and life-style factors were also analyzed. RESULTS: The expression of miR-27a was significantly higher in cervical intraepithelial neoplasia (CIN)2-3 compared to CIN1 (p=0.023) and in squamous cell carcinoma (SCC) compared to CIN2-3 (p=0.033). Moreover, significantly lower levels of miR-34a were detected in CIN2-3 than in CIN1 (p=0.041) and in SCC than in CIN2-3 (p=0.021). Furthermore, we found significant differences in subjects with multiple HPV in miR-27a (p=0.015) and miR-203 (p=0.025) in CIN2-3 compared to CIN1 and miR-21 (p=0.002), mir-27a (p=0.001) and miR-34a (p=0.001) in SCC/CIN2-3. Expression of miR-27a, showing up-regulation in CIN2-3 compared to CIN1 (p=0.028) and miR-34a (down-regulated), correlated with HPV 16 positivity (CIN2-3/CIN1: p=0.027 and SCC/CIN2-3: p=0.036). MiR-34a expression was also significantly altered in connection to smoking status and presence of HPV 16. CONCLUSION: The demand for additional, alternative molecular biomarkers with prognostic potential is strong. Evaluation of miRNA expression might be helpful to distinguish different cervical lesions and might be able to help in the prediction of HPV infection outcome.

Investigating the clinical potential for 14-3-3 zeta protein to serve as a biomarker for epithelial ovarian cancer.

OBJECTIVE: Recently, 14-3-3 zeta protein was identified as a potential serum biomarker of epithelial ovarian cancer (EOC). The goal of this study was to investigate the clinical potential of 14-3-3 zeta protein for monitoring EOC progression compared with CA-125 and HE4. DESIGN: Prospective follow-up study. SETTING: University of Pecs Medical Center Department of Obstetrics and Gynecology/Oncology (Pecs, Hungary). POPULATION: Thirteen EOC patients with advanced stage (FIGO IIb-IIIc) epithelial ovarian cancer that underwent radical surgery and received six consecutive cycles of first line chemotherapy (paclitaxel, carboplatin) in 21-day intervals. METHODS: Pre- and post-chemotherapy computed tomography (CT) scans were performed. Serum levels of CA-125, HE4, and 14-3-3 zeta protein were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative electrochemiluminescence assay (ECLIA). MAIN OUTCOME MEASURES: Serum levels of CA-125, HE4, and 14-3-3 zeta protein, as well as lesion size according to pre- and post-chemotherapy CT scans. RESULTS: Serum levels of CA-125 and HE4 were found to significantly decrease following chemotherapy, and this was consistent with the decrease in lesion size detected post-chemotherapy. In contrast, 14-3-3 zeta protein levels did not significantly differ in healthy postmenopausal patients versus EOC patients. CONCLUSIONS: Determination of CA-125 and HE4 serum levels for the determination of the risk of ovarian malignancy algorithm (ROMA) represents a useful tool for the prediction of chemotherapy efficacy for EOC patients. However, levels of 14-3-3 zeta protein were not found to vary significantly as a consequence of treatment. Therefore we question if 14-3-3 zeta protein is a reliable biomarker, which correlates with the clinical behavior of EOC.

Assessment of cells in the ascitic fluid of women with ovarian hyperstimulation syndrome: the clinical implications for subsequent ovarian malignancy.

BACKGROUND: Although some studies have reported a potential connection between ovulation induction therapy (OIT) and malignant ovarian diseases, the results have been inconclusive. In the present study, we sought to determine whether women undergoing OIT at our in vitro fertilization (IVF) clinic, especially those with severe ovarian hyperstimulation syndrome (OHSS) and suspicious cytologic findings, were at risk for developing malignant ovarian tumours after treatment. METHODS: Patients who underwent OIT at our IVF clinic were enrolled in this study and assessed for any evidence of malignant ovarian tumours. Patients who developed severe OHSS as a result of OIT were treated with a culdocentesis. Cells from the ascitic fluid were cytologically scored for abnormality and malignancy. Peripheral blood samples were obtained from patients with severe OHSS to determine serum levels of the tumour markers (CA-125 and HE4) that were used to calculate the Risk for Ovarian Malignancy Algorithm (ROMA) index. RESULTS: Follow-up data were available for 1,353 of the 1,587 patients (85%) who underwent OIT at our IVF clinic between January 2006 and December 2012. Twenty-three patients (1.4%) were hospitalized with OHSS. Culdocentesis was performed 16 times in nine patients with severe OHSS (age range, 23-34 years; mean, 27.1 years). Although cytological examination of the ascitic cells of these patients suggested malignant ovarian neoplasia, over the course of the observation period, the ovarian volume gradually decreased and became normal. Subsequent cytological and histological examinations failed to find evidence of any malignant tumours in these nine patients. None of the 1,353 participants who underwent OIT developed any malignant ovarian tumours during the study period. Moreover, none of the 462 patients who were in our ovarian tumour registry were also participants in the IVF program. CONCLUSIONS: The presence of atypical cells in the ascitic fluid of women with severe OHSS does not likely indicate malignancy; therefore, radical surgical intervention is not justified. The risk of malignancy is minimal shortly after OIT. At our centre, OIT has not been associated with any cases of ovarian tumour.

Unique microRNA expression profiles in cervical cancer.

Cervical cancer is the second leading cause of death among female patients with cancer in the world. Our aim was to analyze cervical cancer cases, in the Southwestern Transdanubian Region of Hungary, with regard to human papillomavirus (HPV) genotype and histological and clinical grading. After HPV testing and genotyping, the expressions of eight different pre-microRNAs (miR-21, miR-27a, miR-34a, miR-146a, miR-155, miR-196a, miR-203, miR-221) in formalin-fixed paraffin-embedded (FFPE) primary human cervical cancer samples were evaluated with the help of the LightCycler 480 PCR System (Roche). Statistically significant overexpression of miR-21 (p=0.004), miR-27a (p=0.018), miR-34a (p<0.001), miR-155 (p=0.021), miR-196a (p=0.032), miR-203 (p=0.037) and miR-221 (p=0.017) were observed in squamous cell carcinoma, regardless of HPV status and clinical grading. Significant overexpression of miR-21 (p=0.004), miR-27a (p=0.02), miR-34a (p<0.001), miR-196a (p=0.027) and miR-221 (p=0.031) was characteristic of HPV-positive squamous cell carcinomas in contrast to adenocarcinomas of the same HPV status.

Effect of an educational intervention on Hungarian adolescents' awareness, beliefs and attitudes on the prevention of cervical cancer.

The alarming national data on the mortality and morbidity rates of cervical cancer as well as the results of a Hungarian survey demonstrating adolescents' low level of understanding of human papillomavirus (HPV) infection and HPV vaccination encouraged the authors to conduct an educational intervention. The aim of this survey was to explore the impact of a brief, HPV-focused program on adolescents' knowledge, beliefs and attitudes. A self-administered anonymous questionnaire was completed by 394 male and female adolescents in September, 2010, in Hungary. Half of the students (48.5%) then had a one-off educational intervention on aspects cervical cancer lasting 45 min lesson, while the rest of the participants, the control group, did not have the educational intervention. Three months following the education, both groups were retested using the same questionnaire. Data were analysed using Statistical Package for the Social Sciences (SPSS). Following the education, significant increase was detected in cervical cancer awareness: causal relationship between HPV and cervical cancer (7.9% → 22.1%, p<0.05), or perception of HPV vaccination (61.3% → 85.9%, p<0.05). Similarly, health-related beliefs have enhanced, such as 'HPV may cause cervical cancer' (64.9% → 81.0%, p<0.05) or 'cervical cancer may be prevented by vaccination' (66.5% → 85.3%, p<0.05). Our data also highlighted that Hungarian adolescents have been practising extremely risky sexual behaviour. Nearly half of the sexually active adolescents had engaged in 'one-night relationship' (41.1%) as well as having sexual intercourse without any contraceptive safety measures (44.3%). In addition to providing adolescents with clear and meaningful information about the implications of a HPV infection and addressing their fears of screening and vaccination, health education should focus on promoting safe sex behaviour by promoting the use of condoms and reducing the number of sexual partners to limit the spread of HPV, and also on encouraging the participation in regular cervical screenings, thus reducing the incidence of cervical cancer.

Urinary steroid profile in early pregnancy after in vitro fertilization.

OBJECTIVE: The aim of the study was to compare the levels of urinary steroid metabolites of patients with successful in vitro fertilization and patients who failed to achieve pregnancy. DESIGN: Comparison of urinary steroid profiles prior to oocyte pick-up and three weeks after embryo transfer. SETTING: University hospital. SAMPLE: Eleven women in the same age range with pregnancy after in vitro fertilization and eleven women who failed to achieve pregnancy. METHODS: The standard "long" protocol was used for ovarian stimulation and intracytoplasmic sperm injection for assisted in vitro fertilization. The steroid metabolites in urine samples collected for 24 h were determined by gas chromatography-mass spectrometry. MAIN OUTCOME MEASURES: Steroid metabolite levels in urine samples determined in the early pregnancy period. RESULTS: The levels of androsterone, etiocholanolone, pregnanediol, tetrahydro-11-dehydrocorticosterone and tetrahydro-corticosterone were significantly higher (p < 0.05) in the urine of women with successful pregnancy three weeks after the embryo transfer, while the levels of tetrahydrocortisone, tetrahydrocortisol, allo-tetrahydrocortisol and α-cortolone became higher in the group of patients with unsuccessful pregnancy. CONCLUSIONS: The production of androgens, progesterone and corticoid steroid metabolites is altered in the early pregnancy period after in vitro fertilization.

[Adenoid cystic carcinoma of the uterine cervix]. / A méhnyak adenoid cysticus carcinomája.

This report presents the history of a 35-year-old patient with adenoid cystic cervical cancer stage IIIB. Adenoid cystic carcinoma of the uterine cervix is a rare disease with poor prognosis. Following irradiation therapy, the patient was declared tumor free, and 20 years after diagnosis and treatment, she has no pathological signs or symptoms.

Adolescents' awareness of HPV infections and attitudes towards HPV vaccination 3 years following the introduction of the HPV vaccine in Hungary.

Hungary takes the fourth place regarding the incidence and the fifth regarding the mortality of cervical cancer among the member countries of the European Union, with 500 deaths due to this preventable illness and nearly 1200 new cases diagnosed every year. Although the vaccines have been available for 3 years, the estimated rate of the female population vaccinated against HPV is approximately 10% in the 12-26-year-age cohort. The aim of this study was to determine factors and motivations affecting the uptake of HPV vaccination among Hungarian adolescents. Examining the effects of some possible sociodemographic predictors (age and gender) and the exposure to health information on HPV vaccine acceptability were also focused on, as well as assessing the most trusted sources of information about sexually transmitted diseases (STDs). A nationwide anonymous questionnaire survey with a sample of 1769 students attending public primary or secondary schools was organised by the authors in 16 Hungarian cities and towns. Data were analysed using the Statistical Package for the Social Sciences (SPSS). Adolescents' awareness of HPV was relatively low. Only 35% of the participants reported they had heard about HPV prior to the survey. Almost 70% of the potentially affected study population had not heard about the vaccine previously. Every fourth student did not believe that vaccination against HPV can prevent cervical cancer. If the vaccination was available free of charge, almost 80% of respondents would request it, but in case they had to pay for it, this number would significantly decrease. Significantly better knowledge and also more positive attitudes towards HPV vaccination was found in relation to the number of information sources. The majority of respondents (62-83%) were open for further information about STDs. The main trusted mediators were school-health services (61.3%), education on health at school (49.2%), health professionals (42.2%) and electronic media (24.6%). Since Hungarian adolescent students expect guidance about STDs principally from school health education, an urgent need for well-designed, HPV-focused educational programmes emerges. Launching such programmes would be especially important for the adolescent population to increase their awareness of the risks associated with HPV infection thus reducing the high incidence of cervical cancer in Hungary in the future.

Difficulties in the prevention of cervical cancer: adults' attitudes towards HPV vaccination 3 years after introducing the vaccine in Hungary.

Cervical cancer is one of the most prevalent gynaecological malignancies worldwide. The Hungarian incidence and mortality of this disease take the 4th-5th places within the European Union. A survey including 785 male and female adults was conducted to assess the knowledge and attitudes concerning HPV vaccination. We focused on the difficulties of the primary and secondary prevention of cervical cancer and examined some potential sociodemographic predictors of HPV vaccine acceptability. Our findings have identified some important issues like: incomplete knowledge, intense distrust and financial concerns. Almost half of the college students (45.6%) are unaware of HPV infections. We confirmed previous findings that older age and female gender correlates with better knowledge on STDs, including HPV. We found that greater exposure to health information comes with better knowledge and more positive attitudes towards vaccination. One quarter of survey respondents do not believe that cervical cancer may be prevented by vaccination. More than half of the adults do not trust national health care system and the preparedness of Hungarian doctors. General attitudes towards vaccination are broadly positive, 80% of survey participants had expressed desire towards HPV vaccination, however if there was a need to pay for the vaccination the willingness would decrease by half. Primary prevention through HPV-focused educational programs, clear communication and financial support would be important for public health to reduce the high incidence and mortality of cervical cancer in Hungary in the future.

[From the surgical field to the microscope. A new tool to identify the lymph node specimens in oncologic surgery]. / A mutotol a mikroszkópig. A rendszerezett nyirokcsomóminták azonosításának új eszköze a ráksebészetben.

Oncologic surgery and pTNM staging require systemic removal of the locoregional lymphnodes. While the optimal extent and therapeutical and/or prognostic value of the lymphadenectomy/sampling are debated organ by organ and (sub)speciality by (sub)speciality, relevance of the lymphnode sytem-tumor concept itself is beyond doubt. Loss of information and existence of traps on the "surgical field-microscope" pathway is an international phenomenon, calling for solution. An integrated sterile and disposable lymphnode tray system is presented here for applications in the different fields of cancer surgery of the upper GI tract, retroperitoneum (gynecology, urology) and ear-nose-throat surgery.

Altered urinary profiles of endogenous steroids in postmenopausal women with adenocarcinoma endometrii.

OBJECTIVE: The potential role of androgen metabolism as co-factors in the development of carcinoma endometrii was investigated. DESIGN: The urinary concentration of 23 androgen, progesterone and corticoid metabolites was quantitatively determined by gas chromatography-mass spectrometry with selected ion-monitoring. We obtained 24-h urine samples from 13 patients with adenocarcinoma endometrii and from 10 age-matched normal female subjects. In the course of the urinary steroid determination, we observed changes in the steroid profiles in the disease examined compared to the same age and same sex control group. Profiling urinary steroids has to give comprehensive information about the synthesis of steroids including the glandular and peripheral steroid metabolisms. RESULTS: The concentrations of 16-hydroxy- dehydroepiandrosterone, pregnanediol and pregnenediol were not significantly different in the two groups. The concentrations of androsterone, etiocholanolone, 11beta-hydroxy-androsterone, 11beta-hydroxy-etiocholanolone, pregnanetriol, pregnenetriol, tetrahydrocortisone, tetrahydro-11-dehydrocorticosterone, tetrahydro-corticosterone, allo-tetrahydro-corticosterone, tetrahydrocortisol, allo-tetrahydrocortisol, alpha-cortolone, beta-cortolone and alpha-cortol were significantly lower in the postmenopausal women with adenocarcinoma than in the controls. CONCLUSION: The changes in the concentrations of single metabolites point out the important role of steroid group, thus providing help in the recognition and treatment of diseased states.

The application of 'endovaginal' sonography during a laparoscopy-assisted Vecchietti operation.

BACKGROUND: Many types of operations are described to create a neovagina in a patient with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, that sometimes result in injury of the surrounding organs. Many trials are detailed in the literature to avoid these complications. Our goal was to examine the benefit of 'endovaginal' sonography during a laparoscopy-assisted Vecchietti operation to avoid bladder injuries. METHODS: A neovagina was created in 15 women with MRKH syndrome by the method of Vecchietti assisted by laparoscopy. The method was modified with the use of'endovaginal' sonography, in order to reduce bladder and rectal injuries. The vaginal ultrasound transducer, placed in front of the vaginal dimple, can guide penetration from the perineum into the peritoneal cavity. With this technique, the narrow space between the bladder and rectum can be well identified. RESULTS: All operations were successful, without any complication, forming a well-functioning 8-10 cm long neovagina, allowing easy introduction of two fingers in all cases, and with good quality of sexual life for the couples. CONCLUSION: Creation of a neovagina by any method in MRKH syndrome may sometimes result in injury of the bladder or rectum due to the narrow space between the bladder and rectum. The placement of the endovaginal ultrasound transducer in front of the vaginal dimple seems to be a promising method to avoid these complications during a laparoscopy-assisted Vecchietti operation.

Relationship between adolescent amenorrhea and climacteric osteoporosis.

OBJECTIVES: The relationship between climacteric osteoporosis and disturbances in menstrual cycle during adolescence was examined. METHODS: Seven hundred and seventy-one questionnaires were shared out among women visiting the outpatient department for climacteric complaints for the first time between 2001 and 2004. Questions revealed the age, age at menarche and menopause, the regularity or irregularity of menstrual cycle during adolescence and adult ages. The bone mineral density was examined using the Dual Energy X-ray Absorptiometry (DEXA) method on the lumbar spine. RESULTS: Six hundred and thirty-five of the 771 questionnaires were suitable for analysis. Osteoporosis was observed in 30.1% of the cases. Age, age at the menarche or at the menopause did not alter in the subgroups with or without osteoporosis. The incidence and severity of osteoporosis were significantly higher in patients reporting secondary amenorrhea during adolescent ages (42.1%; average BMD of the lumbar spine 71.6+/-3.9), as compared to the patients with normal cycle (30.4%; average BMD of the lumbar spine 84.8+/-7.8). No correlation between the occurrence of osteoporosis and the frequency of menstrual cycle during adulthood was observed. CONCLUSIONS: Secondary amenorrhea during the years of adolescence might play a role in the development of more severe osteoporosis in menopause.

Phosphorylation of PTEN (phosphatase and tensin homologue deleted on chromosome ten) protein is enhanced in human fibromyomatous uteri.

PTEN phosphatase, a product of PTEN tumor suppressor gene, exists in cells in phosphorylated and unphosphorylated form and has a central role in regulation of PI3K/Akt signalling which is involved in non-genomic action of estradiol. The purpose of this study was to analyze the level of total PTEN and phosphoPTEN parallel to phosphoAkt in leiomyoma and adjacent myometrium during menstrual cycle and at menopause. The expression of total PTEN in leiomyoma and myometrium did not change throughout the experiments. However, the level of phosphoPTEN was increased in leiomyoma during menstrual cycle. The phosphorylation of PTEN in myometrium was lower during secretory phase than that of proliferative phase. The phosphoAkt was abundant in leiomyoma, and its expression was higher during menstrual cycle than in myometrium. The phosphorylation of PTEN was directly related to phosphoAkt, suggesting a direct link between the inactivation of PTEN and activation of Akt. At the decline of sexual steroids, at menopause, no differences were observed in the expression of studied proteins between the two types of tissues. Our results suggest that the altered phosphorylation of PTEN protein and the consequent activation of survival signals may contribute to the pathomechanism of leiomyoma.