Malignancies are one of the leading causes of mortality in women during their reproductive life. Treatment of gynecological malignant tumors during pregnancy is possible but not simple, since it creates a conflict between care of the mother and the fetus. BC is the most prevalent malignancy diagnosed in pregnancy, ranking up to 21% of all pregnancy-related malignancies. Due to its stets increasing prevalence, aggressive cancer subtype, and severe ethical and psychological aspects linked to the disease, experts raise an alarm for an acute necessity to improve the overall management of the PABC-the issue which has strongly motivated our current paper. Comprehensive research data and clinical experience accumulated in recent years have advanced our understanding of the disease complexity. PABC treatment must be individualized with an emphasis on optimal care of the mother, while observing standard treatment protocols with regard to safety of the fetus. Treatment protocols should be elaborated based on the individualized patient profile, bearing in mind the acute danger to the mother, maximizing the therapy efficacy and minimizing harmful effects to the fetus. Complex consulting on treatment options, their impacts on pregnancy and potential teratogenic effects requires tight "doctor-patient" collaboration. Complications that may arise due to the treatment of breast cancer in pregnancy require a multiprofessional expertise including oncologists, neonatologists, perinatologists, obstetricians, teratologists, and toxicologists, and an extensive psychological support throughout the pregnancy and after giving birth. Thereby, specifically psychological aspects of PABC diagnosis and follow-up are frequently neglected, being not yet adequately explored in the entire disease management approach. Herewith, we update the status quo regarding the currently available diagnostic modalities, complex treatment algorithms, and novel clinical approaches which altogether argue for an urgent necessity of a paradigm shift moving away from reactive to predictive, preventive, and personalized medical approach in the overall management of PABC meeting the needs of young populations, persons at high risk, affected patients, and families as the society at large.
The gene expression profile of breast cancer has been described as a great breakthrough on the way to comprehend differences in cancer origin, behavior and therapy. However, gene expression profile in histologically normal epithelium (HNEpi) which could harbor genetic abnormalities predisposing breast tissue to develop malignancy was minor scope for scientists in the past. Thus, we aimed to analyze gene expressions in HNEpi and breast cancer tissue (BCTis) in order to establish its value as potential diagnostic marker for cancer development. We evaluated a panel of disease-specific genes in luminal type (A/B) of breast cancer and tumor surrounding HNEpi by qRT-PCR Array in 32 microdissected samples. There was 20.2 and 2.4% deregulation rate in genes with at least 2-fold or 5-fold over-expression between luminal (A/B) type breast carcinomas and tumor surrounding HNEpi, respectively. The high-grade luminal carcinomas showed higher number of deregulated genes compared to low-grade cases (50.6 vs. 23.8% with at least 2-fold deregulation rate). The main overexpressed genes in HNEpi were KLK5, SCGB1D2, GSN, EGFR and NGFR. The significant differences in gene expression between BCTis and HNEpi samples were revealed for BAG1, C3, CCNA2, CD44, FGF1, FOSL1, ID2, IL6R, NGFB, NGFR, PAPPA, PLAU, SERPINB5, THBS1 and TP53 gene (p < 0.05) and BCL2L2, CTSB, ITGB4, JUN, KIT, KLF5, SCGB1D2, SCGB2A1, SERPINE1 (p < 0.01), and EGFR, GABRP, GSN, MAP2K7 and THBS2 (p < 0.001), and GSN, KLK5 (p < 0.0001). The ontological gene analyses revealed high deregulations in gene group directly associated with breast cancer prognosis and origin.
Cervical cancer is the fourth leading cause of cancer mortality in females worldwide. Infection with high-risk human papillomavirus (HPV) is essential but insufficient to cause cervical cancer, and the clearance of HPV infection is mediated by the immune system. The deficit of molecules responsible for adhesion may play a role in the development of cervical cancer. E-cadherin is encoded by the cadherin 1 (CDH1) gene, and is involved in cell adhesion by forming adherens junctions. The aim of present study was to investigate the methylation pattern of the CDH1 promoter and to identify the association between CDH1 promoter hypermethylation, CDH1 gene expression and HPV infection in cervical specimens obtained from 93 patients with low-grade squamous intraepithelial lesions (SILs), high-grade SILs or squamous cell carcinomas, and from 47 patients with normal cervical cytology (HPV-negative). The methylation pattern of the CDH1 promoter was investigated by methylation-specific polymerase chain reaction and quantitative pyrosequencing. CDH1 gene expression was measured by relative quantification. CDH1 methylation was significantly higher in both types of lesions and in cervical cancer than in normal samples, and CDH1 gene expression was significantly reduced during SIL progression (P=0.0162). However, the influence of HPV infection or HPV E6 expression on the methylation pattern of the CDH1 gene or its gene expression levels could not be confirmed. The present results support that the methylation of the CDH1 gene is age-related in patients with cervical lesions (P=0.01085), and therefore, older patients could be more susceptible to cancer than younger patients. The important methylation of the CDH1 promoter occurred near the transcription factor binding sites on nucleotides −13 and +103, which are close to the translational start codon. These results suggest that methylation at these sites may be an important event in the transcriptional regulation of E-cadherin, and in patients harboring these methylated cytosines, this event may facilitate HPV-driven carcinogenesis.
The authors present a case of 38-year-old laboring woman with four-time repetitive breech presentation of the fetus at term. This rare condition affects the mode of delivery and represents serious obstetrical problem as it is associated with increased perinatal morbidity or mortality. The authors give details on risk factors for breech presentation, its diagnosis, and the discussion points on possible causes leading to repetitive breeches in laboring women.
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