Tomasz Stetkiewicz

Polymorphism of the ERα and CYP1B1 genes in endometrial cancer in a Polish subpopulation

Aim:  Metabolic activation of estrogens may play a role in endometrial carcinogenesis; and polymorphism of the genes (whose product is involved in this process) may be associated with the modulation of the risk of endometrial cancer. CYP1B1 plays a major role in the metabolism of estrogens, which must firstly bind their receptors, estrogen receptor alpha (ERα) or ER beta. In the present study we investigated the association of two polymorphisms of the CYP1B1 gene (Arg48Gly [142C > G] and Leu432Val [4326C > G]) and a polymorphism of the ERα gene (975C > G) as well as a combination between them with endometrial cancer occurrence.

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.

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.

The role of angiogenic factors in endometrial cancer

Endometrial cancer is the most common malignancy within the female reproductive system (37.7%). The incidence increases with age. Frequently this type of cancer is diagnosed in peri- and post-menopausal women. 60-70% of cancers occur in women over 60 years of age, and less than 5% in women below 40 years of age. Angiogenesis is a process of formation of new microvessels from existing capillaries. There are four different mechanisms of new vessel growth: sprouting, intussusception, vessel elongation and incorporation of endothelial progenitor cells into new microvessels. Angiogenesis plays important roles in growth of endometrial cancers. This process is controlled by many angiogenic factors, for example vascular endothelial growth factor (VEGF). VEGF is the most powerful and most specific endothelial cell growth factor. It plays a crucial role in the initiation of physiological and pathological angiogenesis, lymphangiogenesis, and vasculogenesis. The VEGF family consists of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F and PLGF (placental growth factor). The effects of VEGF are mediated through binding to the two specific and homologous receptors VEGFR-1 (FLT-1) and VEGFR-2 (KDR). Placental growth factor (PLGF) belongs to the VEGF family and it is also a very important growth factor. So far four isoforms of PLGF have been identified: PLGF-1 (PLGF131), PLGF-2 (PLGF152), PLGF-3 (PLGF203) and PLGF-4 (PLGF224).

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.

Hemostatic variables, carbohydrate metabolism and lipid profile in women with low body mass index.

The aim of this study was to evaluate hemostatic variables in women according to different body mass index (BMI) values ,and then correlate them with some metabolic parameters - fasting insulin and glucose, total cholesterol ,high-density lipoprotein (HDL)-cholesterol ,low-density lipoprotein (LDL)-cholesterol and triglycerides. Eighty-four female patients aged 18-39 years were recruited ,and agreed to participate in the study. The study group was divided into three subgroups according to BMI: low BMI (BMI < 18.5 kg/m2; n = 43) ,normal-weight (control) (BMI 18.5-24.99 kg/m2; n = 21) and overweight/obese (BMI > 25 kg/m2; n = 20). BMI was calculated ,and the following measurements were taken: International Normalized Ratio ,antithrombin III ,tissue plasminogen activator (t-PA) activity ,t-PA-antigen, plasma fibrinogen level ,factor VII ,Plasminogen activator inhibitor (PAI)-1 activity and antigen and metabolic parameters: fasting insulin and glucose ,total cholesterol ,HDL-cholesterol ,LDL-cholesterol and triglycerides. The results were statistically analyzed. In the low BMI group ,a negative correlation between fasting insulin and PAI-1 activity ,and a positive correlation between fasting glucose and PAI-1 antigen were observed. Also ,a strong negative correlation between PAI-1 activity and insulin/glucose index was found. Plasma insulin levels were significantly lower in the low-BMI women than in the overweight/obese group (p < 0.001) and with no difference compared to the control group. We did not find any difference in fasting glucose level between all groups. HDL-cholesterol showed the highest levels in the normal BMI group and was significantly higher than in the low BMI and obese groups (p < 0.05 and p < 0.01 ,respectively). PAI-1 activity in the low BMI women revealed increased activity in comparison to control and overweight/obese women (p < 0.001 and p < 0.05 ,respectively). Lower antigen levels were also shown as compared to both these groups (p < 0.001 and p < 0.001 ,respectively). Similar results were obtained with t-PA antigen levels (p < 0.001 and p < 0.001 ,respectively). There were no differences in activity of t-PA in all groups. Obese women showed significantly higher fibrinogen levels than other BMI groups (p < 0.001 and p < 0.001 respectively). Analysis of hemostatic variables in women with a low BMI testify to the impaired fibrinolysis in this group ,also showing a strong correlation with carbohydrate metabolism.

2D/3D ultrasonography for endometrial evaluation in a cohort of 118 postmenopausal women with abnormal uterine bleedings

OBJECTIVES 2D/3D transvaginal ultrasonography in evaluation of endometrium in postmenopausal women with abnormal uterine bleedings (AUB). MATERIAL AND METHODS 2D/3D transvaginal ultrasonography (TVU) was performed in 118 menopausal women with AUB. Endometrial volume and thickness, uterine volume and endometrial vascularity were evaluated. Complete histologic evaluation of the endometrium was obtained through dilatation & curettage (D&C) and/or hysteroscopy. Accordingly, patients were divided into 3 groups: controls (no endometrial pathology, n = 49), GI (benign endometrial pathology, n = 37), GII (endometrial carcinoma, n = 32). RESULTS GII had greater thickness and volume of the endometrium, compared to GI and controls. The presence of arterial vascular flow was identified only in GI and GII (51.35% and 93.75%, respectively). Endometrial volume merged together with uterine volume measurements (TVU-3D) showed a strong, statistical significance between GI and GII, allowing differentiation of begin and malignant endometrial pathologies in postmenopausal women. CONCLUSIONS In TVU diagnostics of postmenopausal women with AUB the following play the most significant role: 1) endometrial thickness (TVU-2D); 2) endometrial volume (TVU-3D); 3) uterine plus endometrial volume (TVU-3D); 4) vascularization within the endometrium, allowing to differentiate between pathological and normal endometrium (TVU-2/3D). Evaluation of the endometrial vascularity, both in TVU-2D and TVU-3D technique, does not allow for reliable differentiation between benign lesions and endometrial cancer.

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 cells 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.

Endometrial and cervical cancer: incidence and mortality among women in the Lodz region

Introduction By the early 21st century the most common cancer of female genitals in Poland was cervical cancer. Now endometrial cancer ranks first. The aim of this study was to analyse the incidence and mortality of endometrial and cervical cancer among women in the Lodz region. Material and methods Data on the incidence and mortality of endometrial and cervical cancer among inhabitants of the Lodz region were obtained from the National Cancer Registry and Bulletin of Cancer Cases in the Lodz region. The analysis covered ten consecutive years beginning in 2001. Results The number of new cases reported in 2010 exceeded that observed in 2001 by 181. The standardized incidence rate of endometrial cancer increased by 6.3, while the standardized incidence rate of cervical cancer decreased by 1.4. Conclusions In the years 2001-2010, the incidence of endometrial cancer increased by 88.3% and that of cervical cancer decreased by 6.5% among inhabitants of the Lodz region. In the years 2001-2010, mortality of endometrial cancer increased by 24.5% and that of cervical cancer decreased by 12.6%. In 2010, the highest crude incidence rates in the Lodz region of both endometrial and cervical cancer at 39.1 were recorded in the district town of Piotrków.