Prognosis of Stage I Endometrial Cancer According to the FIGO 2023 Classification Taking into Account Molecular Changes.

Optimum risk stratification in an early stage of endometrial cancer (EC) combines molecular and clinicopathological features. The purpose of the study was to determine the prognostic value of molecular classification and traditional pathological factors in a sample group of patients with stage I EC according to the FIGO 2023 criteria, to achieve a more personalized approach to patient care and treatment. The immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE exonuclease domain and clinicopathological parameters, including disease disease-free survival (DFS) and overall survival (OS) in 139 patients, were analyzed. It has been shown that the independent recurrence risk factors are stage IC (p < 0.001), aggressive histological types EC (p < 0.001), and the presence of p53abn protein immunoexpression (p = 0.009). Stage IC (p = 0.018), aggressive histological types EC (p = 0.025) and the presence of p53abn protein immunoexpression (p = 0.010) were all significantly associated with lower 5-year OS rates. Our research studies confirm that the molecular category corresponds to a different prognosis in clinical stage I EC according to the new 2023 FIGO classification, with POLEmut cases presenting the best outcomes and p53abn cases showing the worst outcomes. Beyond the previous routine clinicopathological assessment, the new EC staging system represents an important step toward improving our ability to stratify IC stage EC risk.

Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment.

Our increased understanding of tumour biology gained over the last few years has led to the development of targeted molecular therapies, e.g., vascular endothelial growth factor A (VEGF-A) antagonists, poly[ADP-ribose] polymerase 1 (PARP1) inhibitors in hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutants), increasing survival and improving the quality of life. However, the majority of ovarian cancer (OC) patients still do not have access to targeted molecular therapies that would be capable of controlling their disease, especially resistant or relapsed. Chimeric antigen receptors (CARs) are recombinant receptor constructs located on T lymphocytes or other immune cells that change its specificity and functions. Therefore, in a search for a successful solid tumour therapy using CARs the specific cell surface antigens identification is crucial. Numerous in vitro and in vivo studies, as well as studies on humans, prove that targeting overexpressed molecules, such as mucin 16 (MUC16), annexin 2 (ANXA2), receptor tyrosine-protein kinase erbB-2 (HER2/neu) causes high tumour cells toxicity and decreased tumour burden. CARs are well tolerated, side effects are minimal and they inhibit disease progression. However, as OC is heterogenic in its nature with high mutation diversity and overexpression of different receptors, there is a need to consider an individual approach to treat this type of cancer. In this publication, we would like to present the history and status of therapies involving the CAR T cells in treatment of OC tumours, suggest potential T cell-intrinsic determinants of response and resistance as well as present extrinsic factors impacting the success of this approach.

Serum Concentrations of Carotenoids and Fat-Soluble Vitamins in Relation to Nutritional Status of Patients with Ovarian Cancer.

In this study, we aimed to determine serum concentrations of carotenoids and fat-soluble vitamins (FSVs) in ovarian cancer (OC) patients categorized by clinical and nutritional status and to compare obtained results with healthy controls. We used single-step extraction methods throughout the study. Serum concentrations of the bioactive compounds were measured using HPLC. The evaluation of the nutritional status of patients was performed with scored PG-SGA questionnaire.The serum bioactive compound levels were significantly lower in early-stage OC patients (FIGO I/II) when compared to healthy controls for all-trans-retinoic acid, 25-hydroxycholecalciferol, all-trans-retinol, astaxanthin, zeaxanthin, lycopene and α-carotene, respectively. In patients with advanced-stage of OC (FIGO III/IV) the mean serum concentrations of carotenoids and FSVs were significantly lower than in healthy controls, excluding lutein and ß + γ-tocopherol levels. Patients with OC and concomitant moderate or severe malnourishment showed significantly lower levels of 25-hydroxycholecalciferol and all-trans-retinol. It seems that our extraction and measurement methods for the bioactive compounds could be used in both, clinical and nutritional studies. The obtained results confirm that the PG-SGA assessment might be considered not only as a malnutrition assessment tool, but also for planning early nutritional intervention in patients with OC.

Clinical value of selected markers of angiogenesis, inflammation, insulin resistance and obesity in type 1 endometrial cancer.

BACKGROUND: It is a well-known fact show that the risk of developing endometrial cancer (type 1 EC) is strongly associated with obesity. In this study, selected markers, such as obesity, insulin resistance, angiogenesis and inflammation markers related to EC type 1 progression and patients' survival data were analyzed. METHODS: To measure levels of adiponectin, C-reactive protein (CRP), vascular endothelial growth factor-A (VEGF-A), angiopoietin-2 (Ang-2), insulin-like growth factor-1 (IGF-1), insulin and C-peptide in 176 preoperative serum samples, the immunoassay technique (EMIT) has been applied. RESULTS: Angiopoietin-2 levels increase with age (P = 0.005), FIGO stage (p = 0.042), myometrial invasion (P = 0.009) and LVSI (P < 0.001). The CRP levels increase with age (P = 0.01), as well as the advancement of the FIGO stage (P < 0.001), higher tumor grade (P = 0.012), and myometrial invasion (P < 0.001). A positive correlation between serum Ang-2 and CRP levels was demonstrated (r = 0.44; p < 0.001). Kaplan-Meier survival analysis showed that patients with high CRP levels in serum and Ang-2 presented a worse outcome (P = 0.03 and P = 0.015, respectively). Cox regression analysis of individual predictors revealed that high serum levels of Ang-2, CRP, advanced clinical FIGO stage (P < 0.001, respectively), old age (P = 0.013) were all significant overall survival predictors. By means of multivariate analysis, their predictive significance was confirmed. CONCLUSION: Our study provides evidence that serum levels of Ang-2 and CRP may serve as predictors for assessment of the clinical stage of type 1 EC and are significantly associated with poor prognosis. It is likely that angiogenesis and inflammation associated with obesity have a significant impact on EC type 1 progression and survival rate of patients.

Quality of life in long-term survivors of early stage endometrial cancer.

INTRODUCTION: Endometrial cancer (EC) is the most common gynaecological malignancy in developed countries. Effective treatment of the early stage of the disease is achieved by surgery alone. An increasing number of patients with EC become long-term survivors; therefore, the purpose of this study was to investigate the quality-of-life (QOL) of EC survivors. MATERIALS AND METHOD: A total of 328 survivors who had completed cancer treatment more than 3 years ago, and had previously completed questionnaires concerning QOL - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and depression - Beck Depression Inventory-II (BDI-II). Patients were grouped into those with surgery alone or surgery with adjuvant radiotherapy. Responses were compared with 284 healthy women who were seen for standard gynaecologic screening examinations. RESULTS: According to the presented results, the QOL of women with EC after surgical treatment was equal to that of healthy women in the control group. Treatment with adjuvant radiotherapy influenced the QOL, with the exception of emotional functioning (p=0.028). No statistically significant differences were found in scores on the BDI-II between groups for the cognitive-affective factor, the somatic factor, or the total sum score. CONCLUSIONS: The quality of life in EC survivors approximates that of healthy controls after 3 years post-surgical treatment. Patients treated for early stage EC should be informed about the anticipated good prognosis and the low risk of psychosocial and physical long-term effects. Cancer survivors who are treated by surgery and adjuvant radiotherapy may be especially at risk for emotional functioning problems.

Preoperative HE4, CA125 and ROMA in the differential diagnosis of benign and malignant adnexal masses.

BACKGROUND: The aim of this study was to evaluate HE4, CA125 and ROMA in the preoperative differentiation benign ovarian diseases from epithelial ovarian cancer depending on the menopausal status. METHODS: In order to estimate markers' concentrations in the serum of women with benign ovarian disease (n = 128) and with epithelial ovarian carcinoma (n = 96) the electrochemiluminescence (ECLIA) technique has been applied. RESULTS: Using the ROC analysis, although no statistical differences were found among their AUCs, the ROMA algorithm seems to be effective in gathering the diverse performance of HE4 and CA125. The AUC for HE4, CA125 and ROMA for all patients were: 0.895; 0.879 and 0.918, respectively. At established new optimal cutoff values for HE4, CA125 and ROMA we found higher specificity in postmenopausal compared to premenopausal women (96.9 vs 89.8 % and 97.7 vs 84.1 % and 95.9 vs 89.1 %, respectively). The sensitivity of HE4 in pre- and postmenopausal women was similar (83.5 vs 83.8 %), while for CA125 was the highest in premenopausal women (87.0 vs 84.1 %). For HE4, CA125 and ROMA the negative predictive value was high (97.6, 93.9 and 94.4 %, respectively). CONCLUSIONS: The ROMA algorithm shows the best diagnostic performance to distinguish epithelial ovarian cancer from benign ovarian disease. We found the high specificity of HE4 and CA125 while differentiating ovarian benign diseases from epithelial ovarian cancer in postmenopausal women and the high sensitivity of CA125 in detecting epithelial ovarian cancer in premenopausal patients.

Utility of HE4 to identify patients with endometrioid endometrial cancer who may require lymphadenectomy.

PURPOSE: The aim of the study was to establish whether preoperative serum levels of HE4 and CA125 could be a good predictor for lymphadenectomy in the early stage of endometrioid adenocarcinoma of the uterus. MATERIAL AND METHODS: Preoperative serum HE4 and CA125 were measured in 78 postmenopausal patients treated surgically. The ROC curves were generated to determine the optimal cutoff values of HE4 and CA125 levels with optimum sensitivity and specificity for the prediction of lymphadenectomy. RESULTS: Based on ROC curve, we found that the HE4 value of 78pmol/l is the best cutoff to identify candidates who may require lymphadenectomy with the sensitivity of 86.6% and the specificity of 67.2% (NPV=88.4% and PPV=51.2%). The area under the curve (AUC) equals 0.814 (95% CI=0.721-0.886). The cutoff level of CA125 that shows the prognostic indices is 26U/ml, with the sensitivity of 66.6% and the specificity of 61.2% (NPV=69.4% and PPV=44.3%). For CA125 the AUC amounts to 0.671 (95% CI=0.568-0.764). We also found a statistically significant difference, comparing HE4 and CA125 AUC (0.814 vs. 0.671, respectively, p<0.001). The combination of HE4 and CA125 established in our study as the cutoff point has the sensitivity of 81.2% and the specificity of 65.9% with NPV=83.4% and PPV=47.9%. CONCLUSIONS: Our findings indicate that in the early stage of endometrioid endometrial cancer, HE4 can serve as a preoperative tool that can help to identify postmenopausal women who may require lymphadenectomy.

Prognostic significance of pretreatment VEGF, survivin, and Smac/DIABLO serum levels in patients with serous ovarian carcinoma.

The second mitochondria-derived activator of caspase (Smac/DIABLO), vascular endothelial growth factor (VEGF), and survivin are known to play a significant role in the growth and development of numerous tumors. Serum concentrations of VEGF, survivin, and Smac/DIABLO were analyzed in 92 patients with serous ovarian cancer and 94 healthy controls. Values were correlated with clinicopathological characteristics and outcomes. The median pretreatment serum VEGF and survivin levels in patients with serous ovarian carcinoma were significantly higher, while Smac/DIABLO levels were significantly lower than that in healthy controls. Receiver operating characteristic (ROC) curve analysis showed that the best cutoff point for VEGF was determined to be 345 pg/ml; with 83 % sensitivity and 65 % specificity. For survivin, the cutoff point was 110 pg/ml and for Smac/DIABLO was 75 pg/ml, with 82 and 62 % sensitivity and 43 and 87 % specificity, respectively. In the patients group, higher VEGF and survivin levels and lower Smac/DIABLO levels in sera were significantly associated with poorer overall survival (OS) and disease-free survival (DFS). Preoperative measurement of serum VEGF, survivin, and Smac/DIABLO may be of help in early detection of serous ovarian cancer and may provide important information about the patient's outcome and prognosis.

Potential application of curcumin and its analogues in the treatment strategy of patients with primary epithelial ovarian cancer.

Recent findings on the molecular basis of ovarian cancer development and progression create new opportunities to develop anticancer medications that would affect specific metabolic pathways and decrease side systemic toxicity of conventional treatment. Among new possibilities for cancer chemoprevention, much attention is paid to curcumin-A broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of Curcuma longa L. According to ClinicalTrials.gov at present there are no running pilot studies, which could assess possible therapeutic benefits from curcumin supplementation to patients with primary epithelial ovarian cancer. Therefore, the goal of this review was to evaluate potential preclinical properties of curcumin and its new analogues on the basis of in vivo and in vitro ovarian cancer studies. Curcumin and its different formulations have been shown to display multifunctional mechanisms of anticancer activity, not only in platinum-resistant primary epithelial ovarian cancer, but also in multidrug resistant cancer cells/xenografts models. Curcumin administered together with platinum-taxane chemotherapeutics have been reported to demonstrate synergistic effects, sensitize resistant cells to drugs, and decrease their biologically effective doses. An accumulating body of evidence suggests that curcumin, due to its long-term safety and an excellent profile of side effects should be considered as a beneficial support in ovarian cancer treatment strategies, especially in patients with platinum-resistant primary epithelial recurrent ovarian cancer or multidrug resistant disease. Although the prospect of curcumin and its formulations as anticancer agents in ovarian cancer treatment strategy appears to be challenging, and at the same time promising, there is a further need to evaluate its effectiveness in clinical studies.

Serum levels of IL-6, IL-8 and CRP as prognostic factors in epithelial ovarian cancer.

In the present study, associations between pretreatment interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein (CRP) serum levels and epithelial ovarian cancer (EOC) were analyzed using commercially available, enzyme-linked immunosorbent assay (ELISA) in 118 patients and 64 control subjects. Values were correlated with clinicopathological characteristics and outcomes. Control variables included age, stage, grade, histological type and residual tumor size. Kaplan-Meier plots and univariate and multivariate Cox proportional hazards models were used to study the associations between IL-6, IL-8 and CRP levels, control variables, overall survival and disease-free survival. The median IL-6, IL-8 and CRP serum levels in EOC were significantly higher than in the normal control group; 11.5 pg/mL (range, 3.4-62.6) versus 2.9 (1.1-12.3) pg/mL (p<0.001) and 21.8 pg/mL (range, 16.4-105.3) versus 9.3 (4.3-32.4) pg/mL (p<0.001) and 9.51 mg/L (range, 0.3-129.2) versus 1.2 (0.1-11.5) mg/L (p = 0.001), respectively. High levels of IL-6, IL-8 and CRP were associated with reduced overall survival (P = 0.003, P = 0.035, P = 0.046) and disease-free survival (P<0.001, P = 0.026, P = 0.043), respectively. Multivariate analyses showed that IL-6, IL-8 and CRP serum levels independently predicted disease-free survival (P = 0.011, P = 0.001 and P = 0.021), and overall survival (P = 0.004, P = 0.014 and P = 0.016), respectively. EOC is associated with extensive changes in the serum cytokine environment, highlighting the importance of further investigations of relative cytokine level changes. Preoperative serum IL-6, IL-8, and CRP levels seem promising for distinguishing EOC patients from healthy controls; however, their clinical value is still to be confirmed. High levels of IL-6, IL-8, and CRP in EOC patients have been suggested to be a poor prognostic factor for OS and DFS.

Transvaginal electrical stimulation with surface-EMG biofeedback in managing stress urinary incontinence in women of premenopausal age: a double-blind, placebo-controlled, randomized clinical trial.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to evaluate the results of conservative treatment of urodynamic stress urinary incontinence (SUI) using transvaginal electrical stimulation with surface-electromyography-assisted biofeedback (TVES + sEMG) in women of premenopausal age. METHODS: One hundred and two patients with SUI were divided into two groups: active (n = 68) and placebo (n = 34) TVES + sEMG. The treatment lasted for 8 weeks and consisted of two sessions per day. Women were evaluated before and after the intervention by pad test, voiding diary, urodynamic test, and the Incontinence Quality of Life Questionnaire (I-QOL). RESULTS: Mean urinary leakage on a standard pad test at the end of 8th week was significantly lower in the active than the placebo group (19.5 ± 13.6 vs. 39.8 ± 28.5). Mean urinary leakage on a 24-h pad test was significantly reduced in the active group at the end of 8th and 16th weeks compared with the placebo group (8.2 ± 14.8 vs. 14.6 ± 18.9 and 6.1 ± 11.4 vs. 18.2 ± 20.8, respectively). There was also a significant improvement in muscle strength as measured by the Oxford scale in the active vs the placebo group after 8 and 16 weeks (4.2 vs 2.6 and 4.1 vs 2.7, respectively). No significant difference was found between groups in urodynamic data before and after treatment. At the end of 8th week, the mean I-QOL score in the active vs the placebo group was 78.2 ± 17.9 vs 55.9 ± 14.2, respectively, and at the end of 16th week 80.8 ± 24.1 vs. 50.6 ± 14.9, respectively. CONCLUSION: Our study showed that TVES + sEMG is a trustworthy method of treatment in premenopausal women with SUI; however, its reliability needs to be established.

Pretreatment serum levels of bFGF and VEGF and its clinical significance in endometrial carcinoma.

OBJECTIVE: In this study, we examined the frequency of serum elevation as well as the prognostic significance of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in endometrial cancer (EC) type I and a biologically aggressive variant of EC type II. MATERIALS AND METHODS: Pretreatment serum levels of bFGF and VEGF were evaluated by commercially available enzyme-linked immunosorbent assay (ELISA) for cancer patient samples with type I EC (n=70) and type II EC (n=64) and compared to a cohort of normal individuals (n=64). Values were correlated with clinicopathological characteristics and outcome. RESULTS: Median pretreatment VEGF values were 470.4pg/ml (range, 164.3-598.4pg/ml) for type I EC, 608.8pg/ml (range, 354.2-783.6pg/ml) for type II of EC patients and 215.6pg/ml (range, 128.3-332.9pg/ml) for normal healthy subjects (p<0.001). Elevated serum VEGF concentration correlated significantly with advanced FIGO stage in type II EC (p=0.011). Median values of bFGF were 10.7pg/ml (range, 0.5-22.5pg/ml) for type I EC, 21.2 (range, 0.5-62.4pg/ml) for type II EC and 1.1 (range, 0-7.2pg/ml) in controls (p<0.0001). The pretreatment bFGF levels correlated with advancing tumor stages in types I and II EC (p <0.05). Multivariate analysis with Cox proportional hazard regression models revealed that high bFGF serum level correlated with shorter overall survival (OS) in type I EC (HR, 0.39, p<0.001) and in type II EC (HR, 0.47, p=0.01) and disease-free survival (DFS) (HR, 0.53, p=0.03 and HR, 0.51, p=0.02, respectively). CONCLUSION: High preoperative bFGF levels predict a poor prognosis in patients with EC, and the prognostic value is independent of established prognostic parameters. These data suggest that bFGF might potentially serve as a marker in prognosis and offer a possibility to individualize treatment regimen.

Serum levels of VEGF and VEGF-C in patients with endometrial cancer.

Endometrial cancer (EC) is the most common type of uterine cancer. A dualistic model of endometrial tumorigenesis serves as a useful way of categorizing these cancers in terms of both etiology and clinical behavior. There are two types of EC: type I and type II. Type I is so-called estrogen-dependent, and appears mostly in pre- and perimenopausal women, it is well differentiated and therefore has a better prognosis. Type II EC is estrogen-independent, diagnosed mostly in postmenopausal women, thin and fertile women, or in women with normal menstrual cycles. It is aggressive and has a worse prognosis than type I. The aim of this study was to evaluate the relationship between the pretreatment serum levels of VEGF and VEGF-C and the outcome of EC patients. A total of 98 patients treated between 1999 and 2003 were included in this study. Circulating VEGF and VEGF-C levels were determined using ELISA kits. VEGF levels among the 76 patients with type I, and the 22 patients with type II EC were significantly higher than those found in the healthy control subjects (p < 0.001). The differences in mean values of VEGF-C were highly significant in both types of tumor examined compared to the control (p < 0.001). The results demonstrate that serum VEGF concentration correlated significantly with advanced FIGO stage in type II EC (p < 0.001). The preoperative VEGF-C level correlated with advancing tumor stages in type I EC (p < 0.05). An elevated preoperative VEGF-C was an independent risk factor for disease-specific survival in patients with type II tumors. Thus, in type II EC patients with high preoperative levels of VEGF-C, pelvic and para-aortic lymphadenectomy should be performed. However, the value of longitudinal measurements of the markers used is yet to be determined.

The prognostic significance of the immunohistochemical expression of P53 and BCL-2 in endometrial cancer.

The objective of this study was to verify the frequency of P53 and BCL-2 immunohistochemical expression in 98 patients with endometrial carcinoma, and to correlate it with clinical stage and patient survival. A significant difference was found regarding the frequency of P53 expression when comparing type I and II tumors (23.7% and 54.5%, respectively; p = 0.006). A positive correlation was observed between P53 immunoexpression and patient survival in type I and II tumors (p = 0.009 and p = 0.036, respectively). BCL-2 expression was significantly more frequent in early clinical stages in both types of endometrial cancer (p 〈 0.001 and 0.002) and correlated with a decrease in overall survival in type I endometrial cancer (p = 0.014). Thus, the prognostic value of these biomarkers in endometrial cancer needs to be further investigated.

Biomarkers as prognostic factors in endometrial cancer.

Endometrial cancer is the most common gynecologic malignancy in more developed countries. Approximately 75% of cases are diagnosed at an early stage with a tumor confined to the uterine corpus. Although most patients are cured by surgery alone, about 15-20% with no signs of locally advanced or metastatic disease at primary treatment recurs, with limited responsiveness to systemic therapy. The most common basis for determining the risk of recurrent disease has been classification of endometrial cancers into two subtypes. Type I, associated with a good prognosis and endometrioid histology and type II, associated with a poor prognosis and non-endometrioid histology. This review will focus primarily on the molecular biomarkers that have supported the dualistic model of endometrial carcinoma and help determine which patients would benefit from either adjuvant therapy or more aggressive primary treatment.

Prognostic significance of VEGF and its receptors in endometrioid endometrial cancer.

BACKGROUND: Angiogenesis is of crucial importance for endometrial tumor growth and Vascular Endothelial Growth Factor (VEGF) is the key mediator of angiogenesis. OBJECTIVE: The purpose of our study was to assess the prognostic value of VEGF and its receptors in relation to endometrioid endometrial carcinomas. MATERIAL AND METHODS: In this study we conducted an immunohistochemical evaluation of VEGF and VEGFRs expression in 84 tissue samples obtained from endometrioid endometrial cancer patients undergoing curative surgical treatment. RESULTS: Out of 84 cancers, strong positive expression of VEGF was seen in 35 (42%) tumors. The overall strong positive rates were 33% for VEGFR-1 and for 15% for VEGFR-2. There was a significant correlation between clinical stage and VEGF and VEGFR-1 overexpression (p=0.027 and p=0.004, respectively). Additionally there was a significant correlation between histological grade and VEGF and VEGFR-1 overexpression (p<0.001 and p<0.01, respectively). The 5-year DFS of patients with VEGF and VEGFR-1 overexpression was significantly lower than that of those with a weakly positive or negative tumor (p<0.001). CONCLUSION: Immunohistochemical evaluation of VEGF and VEGFR-1 overexpression may be a useful marker for predicting 5-year DFS in endometrioid endometrial cancer.

Prognostic significance of smac/DIABLO in endometrioid endometrial cancer.

Apoptosis may occur via a death receptor-dependent or independent (mitochondrial) pathway. The mitochondrial pathway is regulated by small molecules, such as smac/Diablo, which activates caspase cascades. This study examined smac/DIABLO expression in 76 patients with endometrioid endometrial cancers. Presence of smac/DIABLO was quantified by Western blot analysis using nonfixed fresh frozen tissues. Its appearance was found in 55 (72%) of examined tumors. Smac/DIABLO expression significantly correlated with tumor grade (p<0.001). Patients with positive smac/DIABLO tumors had a longer disease-specific survival when compared with those with negative tumors in the 10-year follow-up (p=0.043). The study demonstrated that negative smac/DIABLO expression was a poor prognostic sign.

Circulating free DNA, p53 antibody and mutations of KRAS gene in endometrial cancer.

This study was conducted to evaluate the significance of circulating free DNA (CFDNA), p53 antibody (p53-Ab) and mutations of KRAS gene in the development of endometrial cancer (EC). A total of 109 patients with EC (87 patients with Type I and 22 patients with Type II) took part in this study. KRAS mutations and CFDNA were detected by means of the PCR-RFLP and enriched by the PCR-RFPL method. ELISA was used to analyze plasma p53-Ab. Tissue expression of P53 protein was evaluated immunohistochemically (IHC). The frequency of KRAS mutations was especially high in Grade 2 of Type I EC. CFDNA was frequently detected in patients with early stage of Type II EC at a low level of grade. It is noteworthy that the p53-Ab positive rate increased in the higher grade of Type I tumors. A significant difference in the number of cases with the p53-Ab was found in the advanced stage of Type I tumors. The frequency of KRAS and p53-Ab correlates with tumor stage only in the Type I EC. Plasma CFDNA and p53-Ab offer a chance to develop a procedure for EC Type II diagnosis. The association between tumor cells related to CFDNA and p53-Ab with Type II tumor suggests that it might potentially serve as a marker in predicting the prognosis and offers a possibility to individualize treatment regimen.

Mutations in the KRAS gene in ovarian tumors.

RAS genes are the most frequently mutated oncogenes detected in human cancer. In this study we analyzed the presence of mutations at codon 12 of the KRAS gene in 78 women with ovarian tumor, including 64 invasive ovarian cancers and 14 borderline ovarian tumors, using an RFLP-PCR technique and we evaluated whether such alterations were associated with the selected clinicopathological parameters of the patients. KRAS codon 12 gene mutations were found in 6,2% of ovarian cancer tissue and in 14,3% of the borderline ovarian tumor. KRAS mutations were found with a significantly higher frequency in mucinous and borderline tumors compared to serous tumors (p<0,01). Mutation frequency was correlated with the histological type of tumor, but not with stage, grade or patients age.

Circulating levels of TNF-alpha and its soluble receptors in the plasma of patients with epithelial ovarian cancer.

The significance of circulating levels of TNF-alpha and its soluble receptors (sTNF-Rs) in the plasma of patients with epithelial ovarian cancer (EOC) has not been fully elucidated. The present study was to investigate the relationship of pretreatment plasma levels of TNF-alpha, sTNFR-1 and sTNFR-2 with outcome in 126 patients with EOC. Concentrations of TNF-alpha and sTNF-Rs were determined by enzyme-linked immunosorbent assay (ELISA). Median TNF-alpha and sTNF-Rs levels were significantly higher in EOC patients than in healthy controls. High plasma levels of TNF-alpha and sTNF-Rs were correlated with tumor stage and with reduced mean survival time (MST). The results of the present study suggested that preoperative plasma TNF-alpha and sTNF-Rs levels in EOC patients correlated with the highest risk of cancer progression. Thus, the clinical value of an activated TNF system in EOC needs to be further investigated.