Colposcopic scoring indexes in the evaluation of cervical lesions with the cytological result of atypical squamous cells, cannot exclude high-grade lesion.

AIM: Colposcopic indexes including Reid index and Swede score were developed to make the colposcopy more objective. The aim of our study was to evaluate the significance of colposcopic indexes in the evaluation of ASC-H cervical lesions. METHODS: We carried out a cross-sectional study in the Clinic of Obstetrics and Gynecology between January 2013 and December 2018. The study included 535 women, from which 66 women had a cytological result ASC-H. Scoring of all colposcopic findings was assessed according to Reid modified index and Swede score and a composite score was determined. Frequency distributions were compared using χ2 /Fisher exact test. Spearman rank correlation coefficient was computed between RCI and Swede score. RESULTS: Sensitivity, specificity, positive and negative predictive value and positive likelihood ratio of modified Reid colposcopic index at a cutoff of ≥4 for the detection of HSIL+ lesions were: 86.11% (95% CI: 70.5-95.3), 83.33% (95% CI: 65.3-94.4), 86.11% (95% CI: 69.7-94.8), 83.33% (95% CI: 64.5-93.7) and 5.17 (95% CI: 2.3-11.6). Swede score with the cutoff value ≥5 showed comparable results to modified Reid index with the increased sensitivity: 94.44% (95% CI: 81.3-99.3). CONCLUSION: ASC-H category represents the trickiest cytological diagnosis as it is underlined with the high risk of severe cervical dysplasia. Evaluating the cervical lesion by the use of colposcopic indices helps the gynecologist to objectively evaluate all the pathologies of uterine cervix. Swede score with the cutoff value 8 also enables a 'see and treat' option in management of atypical squamous cells, cannot exclude high-grade lesions.

Different amplification patterns of 3q26 and 5p15 regions in cervical intraepithelial neoplasia and cervical cancer.

PURPOSE: The aim of this study was to evaluate and correlate the amplification of chromosomal regions 3q26 and 5p15 in different cytological and histological subgroups of patients and to compare the sensitivity and specificity of amplification tests with cytology, colposcopy and HPV status. METHODS: The work was conducted at the Department of Obstetrics and Gynaecology in cooperation with the Institute of Pathological Anatomy, JFM CU in Martin and UNM during years 2013-2016. Prospective longitudinal study included 131 patients. We focused on the FISH diagnosis of the amplification of regions encoding the components of telomerase enzyme (3q26, 5p15) in cytology specimens. We manually evaluated 100 atypical cells per slide and analysed the amplification patterns. Correlations between cytological, histological, HPV DNA results and amplification patterns of chromosomal regions 3q26 and 5p15 were analysed by chi-squared test and non-parametric Man - Whitney U test. RESULTS: The results showed that the amplification of chromosomal regions increases with the degree of dysplasia toward the invasive disease (p < 0.001). Whereas the increase in the amplification of 3q26 is noticeable already at CIN 2 + lesions (p < 0.01), 5p15 amplification is shifted up toward CIN 3/CIS (p < 0.001) and cervical cancer. Amplification of selected regions correlated with each other and also with hrHPV-positive status (p < 0.01). CONCLUSION: The analysis of the amplification of 3q26 and 5p15 regions may serve in the future for the differential diagnosis of cervical lesions and to determine their malignant potential. High specificity of these tests can improve the excellent sensitivity of HPV DNA test.

Molecular and clinical attributes of uterine leiomyomas.

Uterine leiomyomas, also called uterine fibroids or myomas, represent one of the most common benign tumour types in women of a fertile age. Leiomyomas arise due to transformation of the layer of smooth muscle cells of corpus uteri - the myometrium. Despite frequent occurrence of this disease, the molecular mechanisms behind the origin and development of leiomyomas are still relatively unknown. Most predisposed are obese women and women of African origin. In more than half of cases, leiomyomas remain asymptomatic. Genetic factors also have an important impact on the development of these hormone-dependent tumours. However, the clinical and molecular characteristics of familiar and sporadic leiomyomas can widely differ. The main reason is the heterogeneity of this disease and the abundance of factors which can underlie their tumourigenesis. Clinical diagnosis of uterine leiomyomas without surgical interference can be hindered in the case of small, mostly submucosal leiomyomas or if it is necessary to avoid potential malignancy of tumour. Also, medical treatment of uterine leiomyomas cannot be nowadays considered sufficient with many medical agents still being tested only within clinical research. The main goal of this article is to summarise known facts about the aetiology of leiomyomas, risk factors that contribute to their development, known molecular-genetic aberrations connected with the presence of leiomyomas as well as the possibilities of their diagnosis and treatment.

DNA methylation as mechanism of apoptotic resistance development in endometrial cancer patients.

DNA methylation is a significant epigenetic modification which plays a key role in regulation of gene expression and influences functional changes in endometrial tissue. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients. The aim of our study was to examine the promoter DNA methylation changes in 22 apoptosis-associated genes in endometrioid endometrial cancer patients, precancerous lesions and healthy tissue from various normal menstrual cycle phases using a unique pre-designed methylation platform. We observed as the first a significant difference in promoter DNA methylation status in genes: BCL2L11 (p < 0.001), CIDEB (p < 0.03) and GADD45A (p < 0.05) during endometrial carcinogenesis and BIK gene (p < 0.03) in different phases of normal menstrual cycle. The results of our study indicate that deregulation of mitochondrial apoptotic pathway can considerably contributes to the apoptosis resistance development and may be helpful in identifying of new potent biomarkers in endometrial cancer.

Survival and risk factors associated with uterine sarcomas and carcinosarcomas in stage I and II.

OBJECTIVE: Uterine sarcomas are rare mesodermal malignant tumors with an incidence between 0.5 and 3.3 cases per 100,000 females per year. Most sarcomas are aggressive tumors leading to poor overall survival rates and only limited therapeutic options. The aim of this study was to evaluate the risk factors for uterine sarcomas and carcinosarcomas, and to identify the factors influencing the survival rate. SUBJECTS AND METHODS: We conducted a retrospective study with twenty-nine patients who were diagnosed with uterine sarcoma and thirty-four patients with carcinosarcoma between the years 1990 and 2006 at the Oncogynecologic center at the University Hospital in Martin, Slovakia. We focused on the analysis of the risk factors and survival rate of early stages I and II. RESULTS: We confirmed highly statistically significant values for the inverse correlation between survival and tumor size, positive lymph nodes, high mitotic activity, vascular invasion, positive peritoneal cytology, elevated CA-125, smoking and BMI in sarcoma and carcinosarcoma group (p<0.001 for all factors). The use of lymphadenectomy had no effect on survival of all patients. DISCUSSION: Sarcomas and carcinosarcomas are aggressive tumors leading to poor overall survival rates and only limited therapeutic options. As there is no consensus on specific treatment, an individual approach based on evaluation of known risk factors is essential.

Amplification of 3q26 and 5p15 regions in cervical intraepithelial neoplasia.

OBJECTIVE: To analyze different amplification patterns of 3q26 and 5p15 regions in low-grade and high-grade cervical intraepithelial neoplasia. DESIGN: Experimental research. SETTING: Department of Obstetrics and Gynecology at a medical faculty in Slovakia. POPULATION: A group of 83 patients referred for colposcopic examination. METHODS: Amplification of 3q26 and 5p15 regions was analyzed on the 100 most atypical cells from a cervical cytology slide by fluorescent in situ hybridization using a multicolor hybridization probe. Chi-squared and Man-Whitney U-tests were used for statistical analysis. MAIN OUTCOME MEASURES: Liquid-based cytology samples and biopsy samples obtained during colposcopic examination correlated with high-risk human papillomavirus status and with amplification patterns of selected regions analyzed by fluorescent in situ hybridization. RESULTS: The number of cells with 3q26 and 5p15 gain rises with the severity of the lesion p < 0.01. The sensitivity of 3q26 amplification for CIN2+ lesions was 72.1% (95% confidence interval 56.3-84.7) and specificity was 90.0% (95% confidence interval 76.3-97.1). The sensitivity of 5p15 amplification for CIN2+ lesions was 69.8% (95% confidence interval 53.9-82.8) and specificity was 85.0% (95% confidence interval 70.2-94.3). CONCLUSION: Evaluation of telomerase components can help in differential diagnosis of low-grade and high-grade cervical lesions and in individualized management of these patients.

Amplification of TERT and TERC genes in cervical intraepithelial neoplasia and cervical cancer.

OBJECTIVES: Telomerase is activated in various stages of oncogenesis. For cervical cancer, telomerase is already active in precancerous lesions. In our study we focused on the analysis of the amplification patterns of telomerase genes TERT and TERC. DESIGN AND SETTING: We included 39 patients in our study between January 2012 and April 2013. Each patient underwent a classical gynaecological examination and a colposcopy. During the colposcopic examination we collected material for a Pap smear, HPV DNA test (HC2) and LBC (LiquiPrep™), and performed punch biopsies for histopathological evaluation. Residual cytologic sample was hybridized with the FISH probe and telomerase genes were analysed. RESULTS: The amplification of the TERT gene showed us a very similar amplification pattern as TERC and gradually corresponded with both histolopathological (p<0.001) and cytopathological findings (p<0.001). The specificity and sensitivity of TERC gene amplification for the detection of CIN2+ lesions (cut off value 2.3) was 88.2% and 95.5% respectively (PPV 91.3%, NPV 93.8%). CONCLUSIONS: We identified increasing amplification pattern of telomerase genes in cervical lesions. According to our results telomerase genes could help in the future to determine the malignant potential of cervical lesions and could be tested together with cytology and HPV DNA in order to obtain the highest combined sensitivity and specificity for CIN2+ lesion detection.

Detection of methylation of the promoter region of the MAL and CADM1 genes by pyrosequencing in cervical carcinoma.

OBJECTIVE: Cervical cancer is the second most common cancer disease affecting the female population. A key factor in development of the disease is the human papillomavirus infection (HPV). The disease is also impacted by epigenetic changes such as DNA methylation, which causes activation or exclusion of certain genes, and simultaneously the hypermethylation of cytosines in the promoters and turn-off of previously active genes occur. In this study, we focused on the introduction of pyrosequencing for the detection of DNA methylation of the selected CADM1 and MAL genes. METHODS: DNA was isolated from cytological cervical smear of patients with different types of dysplasia [L-SIL (n=14), ASC-US (n=15), H-SIL (n=1)] and four control samples from healthy women. Prepared samples were further analyzed by bisulfite conversion and subsequent pyrosequencing (Pyromark Q96 ID, Qiagen, Germany). We examined the extent of methylation of CpG islands and as control samples of this method we used a fully methylated and unmethylated DNA. Methylation level (Met level) from each sample was quantified as the mean value [sum of all methylated CpG islands in %/total number of CpG islands (MAL n=4; CADM1 n=3)]. RESULTS: In total, 30 clinical samples and 4 control samples from healthy women were analyzed. By means of the analysis of the CADM1promoter region, the values of the Met level were obtained [fully methylated DNA (94.83 and 88); completely unmethylated DNA (0 and 0); and control samples from healthy patients (6.825 and 0.825), L-SIL (2.107 and 2.778), ASC-US (7.313 and 3.626), H-SIL (0 and 0)]. By means of the analysis of the MAL promoter region, the values of Met level were obtained [fully methylated DNA (53.25); completely unmethylated DNA (0.875); and control samples from healthy patients (2.925), L-SIL (1.517), ASC-US (2.833), and H-SIL (4)]. CONCLUSION: We introduced a pyrosequencing method for quantification of methylation of CADM1, MAL promoter regions, and detected methylations in clinical samples and also some basal methylation in healthy women.

Desmoid Fibromatosis of the Anterior Abdominal Wall in Pregnancy: A Case Report and Review of the Literature.

A desmoid tumor (DT) is a rare benign neoplasm arising from muscle aponeurosis, associated mostly with trauma or pregnancy. DT has an infiltrative and locally aggressive growth pattern and usually does not metastasize. However, it has a high recurrence and complication rate. When it occurs in pregnancy, the pregnancy and delivery is taken as an individual case for optimal management by physicians and midwifes, who need to be cautious in finding the optimal delivery mode for the patient, which depends on the tumor size, location, behavior, and past history. The authors report a case of 29-year-old pregnant woman who previously underwent systemic oncological treatment for a large abdominal wall desmoid tumor and became pregnant afterwards. The history of DT presented a follow-up and delivery challenge. Observational management was chosen with an elective cesarean section at week 38 + 4 of pregnancy with uncomplicated postpartum follow-up. The authors detail the clinical management and chosen therapeutic approach; chemotherapy can be a choice in the treatment options for patients with DTs, although the majority of DTs are treated surgically with subsequent mesh plastic. Moreover, the authors provide a systematic review of the literature focused on the treatment management of DTs in pregnant women during pregnancy and the postpartum period, as pregnancy-associated desmoid tumors are a specific condition, where the optimal management is not well established, despite some guidelines for non-pregnant patients.

Hypermethylation of selected genes in endometrial carcinogenesis.

OBJECTIVES: Endometrial cancer is one of the most common malignancies in women. The prevention has failed so far to develop an effective screening program and its incidence is rising in proportion to the incidence of cervical cancer. In recent years the investigation of malignancy genomics (genetic and epigenetic changes) has become the main focus of scientists because of its high sensitivity and specificity. MATERIAL AND METHODS: We conducted a prospective longitudinal study at the Dpt. of Gynaecology and Obstetrics of the Jessenius Faculty of Medicine in Martin from 2010 to 2012, in collaboration with the Institute of Pathology of the University Hospital in Martin. We analysed paraffin blocks of endometrial tissue from 123 women with endometrial cancer, hyperplasia and normal endometrial findings. By the use of bisulphidic modification technique and nested methylation-specific PCR (MSP), we analysed the methylation patterns of three genes: GSTP1, E-cad, RASSF1. RESULTS: We found a statistically significant increase of methylation of the RASSF1 gene in endometrial cancer compared to simplex hyperplasia and intact endometrial tissue (p<0.001). GSTP1 and E-cad did not show any relevant methylation pattern in various endometrial lesions. CONCLUSION: According to the results of our study, RASSF1 gene methylation could serve as a prognostic factor of endometrial carcinogenesis and could help to predict the behaviour of endometrial hyperplasia.

Fungal neuroinfections and fungaemia: unexpected increase of mortality from invasive fungal infections in 2005-2011 in comparison to 1989-1998: analysis of 210 cases.

OBJECTIVE: In this short communication we compared the data of fungaemia cases in Slovak hospitals from 1989-1998 published in 1999-2000 with data from 2005-2011. METHODS: Risk factors, etiology and outcome of fungaemia between two periods (1989-1998 vs. 2005-2011) were compared and risk factors for death assessed by univariate analysis (CDC 2006 Statistical Package). RESULTS: In comparison to 1989-1998 when only amphotericin B and fluconazole has been used (55%), in 2005-2011 only 35.2% patients received FLU, but 26.4% received voriconazole, 22% caspofungin and anidulafungin and about 6.6% lipid formulations of Amphotericin B. In etiology, while in 1989-1998 only 37.1% (115/310) represented non-albicans Candida (NAC) and non-Candida yeasts in 2005-2011 already reached 63.7%. The significant increase of breakthrough fungaemia may be a sign of inappropriate empiric therapy.

Cognitive Functions, Depressive and Anxiety Symptoms After One Year of CPAP Treatment in Obstructive Sleep Apnea.

Objective: The study worked with depressive symptoms, anxiety score and cognitive functions in obstructive sleep apnea (OSA) patients treated with CPAP. Methods: Eighty-one subjects with OSA and without psychiatric comorbidity were treated with CPAP for one year and completed the following scales and cognitive tests: Trail Making Test, Verbal Fluency Test, d2 Test, Beck Depression Inventory-II and Beck Anxiety Inventory. MINI ruled out psychiatric disorder. At the two months check-up, subjects were re-evaluated for depressive and anxiety symptoms, and after one year of CPAP treatment, subjects repeated cognitive tests and scales. Data about therapy adherence and effectiveness were obtained from the patient's CPAP machines. Results: The study was completed by 59 CPAP adherent patients and eight non-adherent patients. CPAP therapy effectiveness was verified in all patients by decreasing the apnea-hypopnoea index below 5 and/or 10% of baseline values. The adherent patients significantly improved depressive and anxiety symptoms. There was also an improvement in overall performance in the attention test; however, performance in many individual items did not change. The adherent patients also improved verbal fluency and in the Part B of the Trail making test. The non-adherent group significantly increased the number of mistakes made in the d2 test; other results were non-significant. Conclusion: According to our results, OSA patients' mood, anxiety and certain cognitive domains improved during the one-year therapy with CPAP. Trial Registration Number: NCT03866161.

Early life experiences and adult attachment in obsessive-compulsive disorder. Part 2: Therapeutic effectiveness of combined cognitive behavioural therapy and pharmacotherapy in treatment-resistant inpatients.

OBJECTIVES: Obsessive-compulsive disorder (OCD) is a chronic mental disorder that is often hard to treat with current treatment options. Therapeutic outcomes are predicted by many factors, ranging from biological to psychosocial. Early life experiences and adult attachment influence the effectiveness of the treatment. This study explores their predictive abilities in the combined treatment of adult inpatients with OCD. METHODS: Seventy-seven patients with OCD, diagnosed according to the ICD-10 criteria, were included in the study, out of which 66 patients completed the treatment. All patients were previously unsuccessfully treated with a minimum of two antidepressants for three months each. They were evaluated with rating scales and questionnaires at the start and the end of a six-week hospitalization in a psychotherapeutic department. The treatment approach presented a combination of group cognitive-behavioural therapy and medication. RESULTS: The average severity of OCD, anxiety and depressive symptoms significantly decreased during the inpatient treatment. The improvement in Y-BOCS negatively correlated with the age of onset. The history of emotional abuse and neglect and physical neglect predicted a lower change in anxiety evaluated by a psychologist and perceived maternal care positively correlated with a decrease in anxiety assessed with a rating scale. Adult attachment anxiety predicted a lower decrease in the anxiety measured by the clinician but not the OCD symptomatology. Dissociative symptoms did not significantly predict a change in any of the measures. Comorbid personality disorder did not have a significant impact on therapeutic change. CONCLUSIONS: The early onset of the disorder was the sole predictor of the treatment outcomes regarding specific OCD symptomatology. Selected early adverse experiences, maternal care, and adult attachment anxiety predicted a change in the anxiety symptoms. Future research should focus on mediation and moderation analyses that could help target specific treatment strategies to decrease the impact of these factors.

Early life experiences and adult attachment in obsessive-compulsive disorder. Part 1: Relationships between demographic, clinical, and psychological factors in pharmacoresistant OCD.

OBJECTIVES: Obsessive-compulsive disorder (OCD) has been connected to various psychosocial factors that might influence its onset and course. Developmental factors, such as parenting styles or early adverse experiences, and adult attachment have been listed as examples. However, the research on the interconnections of these factors brought mixed results. The study explores the relationship between demographic, clinical, and selected psychosocial factors and the severity of adult OCD. METHOD: Eighty-seven pharmacoresistant inpatients with OCD were admitted between October 2019 and August 2022 for a 6-week cognitive behavioural therapy inpatient program in the psychotherapeutic department. The participants completed the following scales at the start of the hospitalisation: the self-report Yale-Brown Obsessive-Compulsive Scale (Y-BOCS-SR), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), Dissociative Experiences Scale (DES), Childhood Trauma Questionnaire-Short Form (CTQ-SF), PBI (Parental Bonding Instrument), ECR-R (Experiences in Close Relationships - Revised), and a demographic questionnaire. A skilled psychologist administered Mini International Neuropsychiatric Interview (MINI) to confirm the OCD diagnosis and Hamilton Anxiety Rating Scale (HAMA). RESULTS: OCD patients with more severe adverse childhood experiences (ACEs) showed earlier onset of the disorder and more pronounced attachment anxiety, depressive symptoms, and dissociation and subjectively rated the severity of the disorder as more severe. Physical abuse and physical neglect were related to the severity of specific OCD symptoms. Maternal care negatively correlates with clinician-rated anxiety, patient-rated depressive symptoms, and dissociation. The maternal and paternal control positively correlated with patient-rated anxiety and depression. Attachment anxiety negatively correlated with the age of onset and positively with the severity of the clinician-rated anxiety and the patient-rated anxiety, depressive symptoms, and dissociation. CONCLUSIONS: Early adverse experiences, perceived parental styles, and adult attachment anxiety could play a significant role in the symptoms of anxiety, depression, and dissociation. The connection with the specific obsessive-compulsive symptoms is less apparent. Still, adverse childhood events and adult attachment anxiety seem to influence the age of OCD onset.

Participation of BKCa2+ and KATP potassium ion channels in the contractility of human term pregnant myometrium in in vitro conditions.

AIM: The aim of this study was to assess the participation of ligand-sensitive potassium large conductance calcium-activated ion channels (BK(Ca2+) ) and adenosine triphosphate (ATP)-sensitive potassium ion channels (K(ATP) ) using its openers (NS1619 and pinacidil) in the contractility of human term pregnant myometrium in in vitro conditions. METHODS: Human myometrium tissue samples were collected from term pregnant laboring women who had to undergo cesarean section. The contractility of myometrium was induced by the application of oxytocin into the organ bath. Myometrial strips were incubated with the opener of BK(Ca2+) potassium ion channels NS1619 and its antagonist tetraethylammonium or with the opener of K(ATP) potassium ion channels pinacidil and its antagonist glibenclamide. RESULTS: K(ATP) potassium ion channel's opener pinacidil significantly decreased amplitude of myometrial contractions (P < 0.05) as well as frequency of myometrial contractions (P < 0.05) provoked by oxytocin in human term pregnant myometrium in in vitro conditions. The inhibition of the human myometrial contractions of pinacidil was significantly antagonized by its specific antagonist glibenclamide (P < 0.05). BK(Ca2+) potassium ion channel's opener NS1619 did not significantly affect the contractile activity of human term pregnant myometrium induced by the application of oxytocin in in vitro conditions. CONCLUSION: In our experimental study we found that the participation of BK(Ca2+) and K(ATP) potassium ion channels in the contractility of human term pregnant myometrium in labor is probably different.

A case of severe dysmelia of all extremities.

A group of limb reduction defects is defined by congenital absence of either part of limbs. We report an extremely rare case of symmetrical upper limb peromelia (absence of distal bones) and asymmetrical lower limb phocomelia (absence of long bones and a flipper-like appearance of feet) in a female fetus at the 20th week of pregnancy. No other malformations were identified. The prevalence of peromelia and phocomelia is extremely rare, and these malformations can be associated with some candidate genes (e.g. de novo apparently balanced reciprocal translocation 46,XX,t(2;12)(p25.1;q24.1)).

The p53 codon 72 exon 4 BstUI polymorphism and endometrial cancer in Caucasian women.

OBJECTIVES: Studies on the association between the p53 Arg72Pro polymorphism and endometrial cancer have reported contrasting conclusions. With the exception of Asian subjects, data demonstrating the influence of this polymorphism on endometrial carcinogenesis in other races/ethnic groups, including Caucasians, are scarce. Thus, we aimed to investigate its role in the development of endometrial cancer and its association with prognostic markers. METHODS: A case-control study examining the p53 codon 72 polymorphism in a total of 451 samples (121 cancer patients, 330 healthy controls) using polymerase chain reaction and sequencing techniques was conducted. Genotypes were correlated with clinico-pathological factors and age. Logistic regression analyses were used to adjust for possible confounding variables, and data were evaluated using the Pearson chi(2) test. RESULTS: We found the Pro allele and genotype frequency to be insignificantly higher in cases than controls (Pro allele: 24.8 and 22.3%, respectively; genotypes: Arg/Pro 36.36 and 34.24%, Pro/Pro 6.61 and 5.15%, respectively). Logistic regression analysis revealed an increased risk for disease in carriers of the Pro allele, with an odds ratio (OR) of 1.13 [95% confidence interval (CI) 0.73-1.76] for heterozygotes and an OR of 1.36 (95% CI 0.56-3.30) for homozygotes. Furthermore, we noted a trend for Arg/Pro + Pro/Pro towards poor tumour differentiation, angioinvasion, pelvic lymph node spread and type II carcinomas, with ORs of 1.27 (95% CI 0.60-2.66), 1.24 (95% CI 0.67-2.30), 1.21 (95% CI 0.53-2.75) and 1.69 (95% CI 0.70-4.10), respectively. Additionally, the Pro genotype was associated with a lower risk for cancer in women with early menarche (OR 1.17, 95% CI 0.60-2.28) and late menopause (OR 0.70, 95% CI 0.30-1.63). Despite the increased or decreased risk observed for some variables, none of these trends were significant. CONCLUSIONS: Our data did not demonstrate any significant difference in the prevalence of the p53 Arg72Pro genotype between patients and controls, providing evidence that this polymorphism is only weakly associated with the risk of endometrial cancer and prognostic factors in Caucasian women.

Different methylation levels in the KLF4, ATF3 and DLEC1 genes in the myometrium and in corpus uteri mesenchymal tumours as assessed by MS-HRM.

Mesenchymal tumours of the corpus uteri comprise common benign lesions - leiomyomas and very rare malignant variants - sarcomas. It can be difficult to distinguish between the particular types of mesenchymal tumours pre-surgically. Primarily, leiomyomas and the very aggressive leiomyosarcomas can be easily misdiagnosed when using only imaging devices. Therefore, a reliable non-invasive marker for these tumour types would provide greater certitude for patients that the lesion remains benign. Our collection comprises 76 native leiomyomas, an equal number of healthy myometrium samples and 49 FFPE samples of various types of sarcomas. The methylation level was assessed by MS-HRM method and we observed differences in the methylation level between healthy, benign and (semi)malignant tissues in the KLF4 and DLEC1 genes. The mean methylation levels of leiomyomas compared to myometrium and leiomyosarcomas were 70.7% vs. 6.5% vs. 39.6 % (KLF4) and 66.1% vs. 14.08% vs. 37.5% (DLEC1). The ATF3 gene was differentially methylated in leiomyomatous and myometrial tissues with 98.1% compared to 76.6%. The AUC values of the predictive logistic regression model for discrimination between leiomyomas and leiomyosarcomas based on methylation levels were 0.7829 (KLF4) and 0.7719 (DLEC1). Finally, our results suggest that there should be distinct models for the methylation events in benign leiomyomas and sarcomas, and that the KLF4 and DLEC1 genes can be considered potential methylation biomarkers for uterine leiomyomas.

Human epithelial growth factor receptor 2[Ile655Val] polymorphism and risk of breast fibroadenoma.

Studies on the association between the Ile to Val polymorphism at codon 655 of the human epithelial growth factor receptor 2 (HER-2) gene and susceptibility to breast cancer have been reported for almost all ethnic populations, with both positive or negative conclusions. No study, however, has yet been focused on the possible association between this gene and its predisposition to benign breast lesions, especially on risk for fibroadenoma. We aimed to study the association of the single nucleotide polymorphism V655 HER-2 gene polymorphism with histologically verified breast fibroadenoma risk. We conducted a molecular epidemiological case-control study of 70 breast fibroadenoma cases without cellular atypia and 172 healthy female controls. We found that the Val variant allele and genotype frequency of this polymorphism is higher in cases with fibroadenoma; however, this difference was not significant (allele Val 655: 27.86 and 22.67% in fibroadenoma and controls, respectively; genotype Ile/Val: 35.71 and 38.37% and Val/Val: 10.0 and 3.49% in fibroadenoma and controls, respectively). Applying logistic regression analysis, we found an increased risk of fibroadenoma formation in carriers of the Val allele (odds ratio = 1.17; 95% confidence interval = 0.67-2.05), in which the highest risk was associated with homozygous genotype (odds ratio = 3.07; 95% confidence interval = 0.97-9.72), but this risk was not significant. Stratification by age (cut-off 45 years) revealed the highest risk of fibroadenoma among young women homozygous for the Val allele (odds ratio = 3.30). The risk, however, was slightly increased (odds ratio = 1.24) among older carriers of the aberrant allele in their genotype as well, but it was not significant. In spite of insignificant differences, our results indicate that HER-2 Ile655Val polymorphism, especially in a homozygous form might play some role in the etiology of breast fibroadenoma formation. The significance of this susceptibility, however, will have to be verified by larger studies.

Spontaneous regression of a breast carcinoma: a case report.

Spontaneous regression of malignant tumors is a rare event. It is defined as partial or total disappearance of a proven malignant tumor without adequate medical treatment. The causes of this phenomenon are various. Nevertheless, malignant tumors do regress occasionally for no apparent reason, as evidenced by many clinical observations. We report a case of a 68-year-old woman, who was presented with a several-month history of a painless firm lump, initially of 1 cm in diameter and growing to a large solid regular tumor of 2.5 x 2.5 cm in size, in the upper outer quadrant of her right breast. Preoperative histopathological diagnosis revealed ductal invasive carcinoma. Later on, while awaiting surgical treatment, she suffered an arm injury requiring a 1-month delay of surgery. After recovery, on the date of surgery the tumor disappeared, and, in addition, it was not found in tissue specimens obtained from quadrantectomy. After 78 months of follow-up there was no evidence of relapse. In this report, we discuss clinical and histopathological findings, patient management and possible mechanisms of cancer regression.