Jozef Visnovsky

Promoter hypermethylation of the tumor-suppressor genes RASSF1A, GSTP1 and CDH1 in endometrial cancer.

Endometrial cancer is a common gynecological malignancy with a good prognosis in early stages of the disease. The CpG island in the promoter region of tumor-suppressor genes are frequently methylated in various types of human cancers. In the present study, we examined the methylation status of the GSTP1, CDH1 and RASSF1A genes in endometrioid endometrial cancer (EEC), endometrial complex hyperplasia (EHP) and healthy endometrium with the aim to identify correlations between promoter hypermethylation, disease risk and clinicopathological parameters. A nested two-stage methylation-specific PCR (MSP) was performed to analyze the promoter CpG methylation status of GSTP1, CDH1 and RASSF1A genes in the population studied. A total of 92 subjects were initially included in the study of which 41 EEC, 19 EHP and 20 controls were processed for final analyses. A significant difference was found between the study groups and the presence of promoter CpG hypermethylation status in the GSTP1 (p<0.05) and RASSF1A (p<0.0001) genes. RASSF1A, GSTP1 and CDH1 gene promoter methylation was present in 85.4, 68.3 and 31.4% of EEC samples when compared to that in the controls with 30.0, 35.0 and 20.0%, respectively. CpG methylation of all three investigated tumor-suppressor genes was found in 12.2% of EEC patients, in 4.2% of EHP patients and in 3.7% of the controls, respectively. Positive findings for the promoter methylation of two investigated genes were found in 48.7% of EEC patients, 26.0% of EHP patients and in 18.5% of the controls. With regard to histopathological variables and CpG methylation, we found significant correlations between the RASSF1A and GSTP1 genes and higher tumor grade, deeper myometrial invasion and positive metastatic involvement of pelvic lymph nodes. No associations were noted between promoter hypermethylation of the CDH1 gene and biological features of the endometrial cancer cases. The results indicate that aberrant CpG methylation of the promoter region in the GSTP1 and RASSF1A tumor-suppressor genes is an important event in carcinogenesis of endometrial cancer and may have an impact on tumor aggressiveness. Finally, the present study suggests that epigenetic alterations may be of diagnostic value for the better clinical management of premalignant endometrial lesions.

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 χ2 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.

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 × 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.

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.

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 (BKCa2+) and adenosine triphosphate (ATP)‐sensitive potassium ion channels (KATP) using its openers (NS1619 and pinacidil) in the contractility of human term pregnant myometrium in in vitro conditions.

Utero‐relaxant effect of PDE4‐selective inhibitor alone and in simultaneous administration with β2‐mimetic on oxytocin‐induced contractions in pregnant myometrium

Background:  The objective of the study was to observe the effect of rolipram, the prototype phosphodiesterase 4 selective inhibitor, on oxytocin‐induced contractions of human term myometrial strips, and compare the effect with salbutamol, β2‐adrenergic agonist, in single and the simultaneous application.

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

To analyze different amplification patterns of 3q26 and 5p15 regions in low‐grade and high‐grade cervical intraepithelial neoplasia.

Atypical ductus venosus blood flow pattern during a prolonged fetal heart rate deceleration in labor

The incidence of atypical ductus venosus (DV) waveforms is under-reported in the literature. We read with interest the article of Smrcek et al.1 on seven cases of atypical DV waveform patterns due to structural cardiac defects. In all seven cases severe tricuspid valve regurgitation was present. Such a phenomenon may be accompanied by systolic notching and may cause reduced peak systolic velocity (S-wave) compared to the peak diastolic velocity (D-wave) in the DV, especially after the conversion from tachycardia to sinus rhythm. Besides such cases with structural heart defects, atypical DV waveforms can be observed as a result of different fetal positions in healthy fetuses2,3. We report on a case with an atypical DV waveform at the very last moments of a term labor, recorded during a prolonged deceleration. At the time of examination the fetal heart rate (FHR) was 80 beats per min (Figure 1). This coincided with a sudden decrease in arterial oxygen saturation, measured by pulse oxymetry, from 40% to values below 10% (Figure 2). A similar characteristic DV pattern was observed by Gudmundsson et al.4 during hypoxemia-induced bradycardia in ovine fetuses. An explanation for this could be that fetal heart rate affects central venous pressure and DV blood flow velocities in a parabolic fashion4. Accordingly, an increase in venous pressure and a corresponding decrease or absence of enddiastolic blood velocities during atrial contraction occur regularly but are dependent on the severity of bradycardia. In our case, a hypoxia-induced deceleration of the FHR (bradycardia) occurred, which lasted several

Uterine activity and ductus venosus flow velocity patterns during the first stage of labor

Objective: To analyze the effects of uterine contractions on ductus venosus (DV) pulsatility during the first stage of labor. Methods: Twenty healthy women were examined. Measurements were taken at three stages of cervical dilatation (< 4 cm, 4–7 cm and ≥ 8 cm) during and between contractions. Peak velocity during ventricular systole (S) and atrial contraction (A), pulsatility index for veins (DV PIV), ductus venosus index (DVI) and the S/A ratio were measured. Results: The DV was observed successfully in 16 cases. The mean S velocity did not change significantly (64 cm/s during and 65 cm/s between contractions). The mean A velocity decreased significantly from 35 cm/s measured between contractions to 29 cm/s during contractions (P < 0.0001). The mean DV PIV and DVI were significantly higher during contractions (0.72 and 0.55) than between contractions (0.57 and 0.45) (P < 0.0001). There were no significant differences in means between stages of cervical dilatation. Conclusion: Significant differences during and between uterine contractions can be observed in DV pulsatility during normal labor.

Delayed delivery following unusual flare-up pelvic abscess after in vitro fertilization and embryo transfer

OBJECTIVE To report a case of delayed delivery of twins following pelvic abscess that required laparotomy after uncomplicated IVF-ET. DESIGN Case report. SETTING Department of Perinatology. PATIENT(S) A 32-year-old nulliparous woman after IVF-ET. INTERVENTION(S) In vitro fertilization and ET, laparotomy, observation in the hospital. MAIN OUTCOME MEASURE(S) Delayed delivery following pelvic abscess that required laparotomy after uncomplicated IVF-ET. RESULT(S) After a successful delayed delivery, the patient and her infant were discharged home. CONCLUSION(S) Pelvic abscess rarely complicates pregnancy. It cannot be excluded in women after IVF-ET. This report confirms the necessity to develop a comprehensive approach for continuation of complicated multiple pregnancies.