Miłosz Wilczyński

Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer

Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients’ clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

The sL1CAM in sera of patients with endometrial and ovarian cancers

PurposeL1CAM is a cell adhesion molecule suspected to play an important role in carcinogenesis. The objective of the study was to evaluate the level of soluble L1CAM in the sera of patients with endometrial and ovarian carcinomas and verify the feasibility of the sL1CAM as a marker of these carcinomas.Methods35 endometrial and 18 ovarian cancer patients were enrolled in the study. 43 patients with benign gynecological conditions constituted a control group. The sL1CAM serum level was measured with ELISA test in each patient and it was referred to the data from the surgical staging of the cancers.ResultsThe sL1CAM serum level was significantly lower in patients with endometrial cancer than in healthy women and slightly lower in the ovarian cancer group than in the control group. In the endometrial cancer group there was no correlation between sL1CAM concentration and cancer histopathology, stage or grade. sL1CAM concentration positively correlated with ovarian cancer stage and (not significantly) with grade.ConclusionsDespite the increasing data about the possible role of L1CAM as a strong prognostic factor of poor outcome in many cancers, we did not find evidence supporting the use of sL1CAM as a marker of endometrial or ovarian cancers.

Supracervical hysterectomy - the vaginal route

Removal of the cervix during hysterectomy is not mandatory. There has been no irrefutable evidence so far that total hysterectomy is more beneficial to patients in terms of pelvic organ function. The procedure that leaves the cervix intact is called a subtotal hysterectomy. Traditional approaches to this surgery include laparoscopic and abdominal routes. Vaginal total hysterectomy has been proven to present many advantages over the other approaches. Therefore, it seems that this route should also be applied in the case of subtotal hysterectomy. We present 9 cases of patients who underwent subtotal hysterectomy performed through the vagina for benign gynecological diseases.

Association of microRNA‐200c expression levels with clinicopathological factors and prognosis in endometrioid endometrial cancer

MicroRNAs (miRNAs) are regulators of gene expression, which play an important role in many critical cellular processes including apoptosis, proliferation and cell differentiation. Aberrant miRNA expression has been reported in a variety of human malignancies. Therefore, miRNAs may be potentially used as cancer biomarkers. miRNA‐200c, which is a member of the miRNA‐200 family, might play an essential role in tumor progression. The purpose of this study was to evaluate the prognostic and clinical significance of miRNA‐200c in women with endometrioid endometrial cancer.

Serum concentrations of soluble (s)L- and (s)P-selectins in women with ovarian cancer

Introduction The aim of the study was to compare serum concentration of soluble L- and P-selectins in women with ovarian cancer (OC) and healthy controls, and to investigate sL- and sP-selectin levels with regard to clinical and pathological parameters. Correlation analysis was used to measure the following: sL- and sP-selectin concentration and Ca125; sP-selectin and platelet concentrations; and sL-selectin and serum leukocyte levels in women with OC. Material and methods The study included 29 patients with OC and 23 healthy controls. Serum concentrations of sL- and sP-selectins were measured in all subjects. Routine diagnostic tests: CBC and USG (both groups) and Ca125 (study group) were performed. Results Significantly higher serum concentrations of sL- and sP-selectins were found in the study group as compared to controls. Lower levels of serum sL-selectin were observed in women with poorly-differentiated OC (G3) and advanced stages of the disease (FIGO III, IV), but the results were statistically insignificant. No statistically significant relationship was detected between sP-selectin serum concentration in women with OC and tumour differentiation, histological type, and stage of the disease. No significant correlation was found between sL- and sP-selectins and Ca125 levels. A weak correlation was found between serum concentration of sP-selectin in women with OC and platelet count. No statistically significant correlation was observed between sL-selectin concentration and serum leukocyte levels in women with OC. Conclusions The analysis of sL- and sP-selectin concentrations may be a useful tool in the diagnosis of OC. The levels of sL-selectin decrease with disease progression.

Ovarian reserve evaluation after laparoscopic cyst enucleation, depending on applied haemostasis technique and with particular consideration of endometrial cysts

Aim of the study was an evaluation of the effects, exerted by obtained haemostasis on ovarian reserve, depending on haemostasis technique, applied after laparoscopic enucleation of endometrial cysts. Material and methods Sixty-six female patients, at the age of 20-35 years, were included into the study. The diameters of the cystic lesions were within 40-70 mm. The patients were randomly assigned to two study groups. Group 1 involved patients after laparoscopic enucleation of ovarian cysts, in whom haemostasis was achieved by ovary suturing, while Group 2 included patients with haemostasis achieved by bipolar coagulation technique. Cyst enucleation was performed in all the patients by the stripping method. Ovarian reserve markers: AFC (antral follicle count), AMH (anti-Müllerian hormone), and inhibin B were assayed before and three months after the surgery. Results The preoperative values of AMH, AFC, and inhibin B were similar in both studied groups. After a three-month follow up, the post-operative levels of AMH and inhibin B were significantly lower (p < 0.05), while the numbers of antral follicles did not reveal any statistical differences (p > 0.05). While comparing endometrial and dermoid cysts in the sutured group of patients, the difference, regarding AMH, was statistically significant (2.13 vs. 4.69, p = 0.03). In the group of patients after bipolar coagulation, the corresponding differences did not attain statistical significance (2.21 vs. 6.51, p = 0.86) Conclusions Comparing pre- and post-operative levels of AMH and inhibin B, regardless of the applied haemostasis technique, a statistically significant reduction of the ovarian reserve was observed in either group. Comparing both haemostasis techniques, no method was demonstrated that would have decreased less the levels of AMH, AFC, or inhibin B.

Does IGF-1 play a role in the biology of ovarian cancer?

OBJECTIVES The aim of the study was to investigate serum concentrations of the insulin-like growth factor-1 in women with ovarian cancer and healthy controls, and to compare free IGF-1 levels with selected clinical and pathological param-eters. Correlation analysis was used to measure the following: IGF-1 concentration and Ca125; IGF-1 level and the height of the OC patients. MATERIAL AND METHODS The study included 70 patients with OC and 50 healthy controls. Serum concentrations of free IGF-1 were measured in all subjects. Routine diagnostic tests (CBC and USG and Ca125) were performed. RESULTS Significantly higher serum concentrations of free IGF-1 were found in the study group as compared to controls. No statistically significant relationships between IGF-1 serum concentrations and tumor differentiation, histological type, and disease stage were detected. No statistically significant correlations between IGF-1 and Ca125 level or between IGF-1 and growth of OC patients were found. CONCLUSIONS Serum IGF-1 participates in the etiopathogenesis of ovarian cancer in menstruating women, while local synthesis of this factor and other components of the autocrine loop of the IGF-1 system play a greater role in their post-menopausal peers.

Expression of miR-146a in patients with ovarian cancer and its clinical significance

The aim of the present retrospective study was to compare microRNA (miR)-146a expression levels in primary tumors and omental metastases of 48 patients, who had undergone surgery for advanced ovarian serous cancer. Possible correlations between miR-146a expression level and clinicopathological features were investigated, including chemosensitivity and survival. miR-146a was evaluated in formalin-fixed, paraffin-embedded samples. miR-146a expression level in primary tumors was demonstrated to be increased in comparison with normal ovary tissues (P=0.02) and metastases (P=0.01). A negative correlation was demonstrated between miR-146a expression in primary tumors and serum levels of cancer antigen 125 (R=-0.37; P=0.03) and Risk of Malignancy Algorithm index (R=-0.79; P=0.0007). Overall survival positively correlated with miR-146a expression in primary tumor tissue samples (R=0.38; P=0.01). Probability of survival was decreased in patients with low miR-146a expression levels in primary tumor tissues (hazard ratio=0.21; P=0.003). Lower levels of miR-146a in primary tumor tissue samples were correlated with a shorter progression-free survival (P=0.04) and platinum-resistance of metastases (P=0.006). In conclusion, miR-146a may be a prognostic marker for serous ovarian cancer.

Pregnancy-related cervical cancer in the material of the Regional Cancer Centre, Łódź, between 2011 and 2014

Introduction. Pregnancy-related cancer is defined as cancer diagnosed during pregnancy or in the first postpartum year. Cervical cancer affects approximately 1 in 1000 pregnant women and is the most common malignancy affecting pregnancy. We retrospectively analysed the clinical outcome and results of treatment in patients with pregnancy-related cervical cancer. Material and methods. We retrospectively analysed the medical records of nine patients with invasive cervical cancer diagnosed during pregnancy and the postpartum period who had been treated in the Regional Oncological Centre, Łodź, between 2011–2014. Results. Three patients with cervical cancer at stage I were diagnosed between the 14 th and 17 th week of pregnancy afterwards and underwent radical surgery. Two patients with cervical cancer at stage Ib who were diagnosed in the 19 th and 24 th week of gestation decided to continue pregnancy until the 30 th and 32 nd week; then a cesarean section combined with radical surgery was performed. In three patients with inoperative cervical cancer diagnosed between the 26 th and 28 th week of pregnancy, a cesarean section was performed at week 30–32. In one patient cervical cancer at stage IIb was diagnosed during the post-partum period. All patients were treated using intensity-modulated radiotherapy (IMRT) to a total dose of 44 Gy/2Gy, weekly cisplatin (40 mg/m 2 ) concurrent with radiotherapy and brachytherapy. No toxicity was observed. During follow-up, two patients with inoperable cervical cancer were diagnosed with a recurrence 2 and 10 months after treatment, respectively. Conclusions. The management of pregnancy-related cervical cancer is mainly determined by the week of the pregnancy and the stage of the disease at diagnosis, but also by the patient choice. The general condition and follow-up of newborns from pregnancies complicated by cervical cancer are similar to those of newborns arising from non-complicated pregnancies. Treatment toxicity is similar in cases with pregnancy-related cervical cancer and in non-pregnant women with cervical cancer. The major prognostic factor in pregnancy-related cervical cancer remains the stage of the disease at diagnosis.

An update of the classical Bokhman’s dualistic model of endometrial cancer

According to the classical dualistic model introduced by Bokhman in 1983, endometrial cancer (EC) is divided into two basic types. The prototypical histological type for type I and type II of EC is endometrioid carcinoma and serous carcinoma, respectively. The traditional classification is based on clinical, endocrine and histopathological features, however, it sometimes does not reflect the full heterogeneity of EC. New molecular evidence, supported by clinical diversity of the cancer, indicates that the classical dualistic model is valid only to some extent. The review updates a mutational diversity of EC, introducing a new molecular classification of the tumour in regard to data presented by The Cancer Genome Atlas Research Network (TGCA).