Objective: This study aimed to evaluate the correlation between the expressions of lung resistance protein (LRP), P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP)-1, MRP3, and MRP5 and histopathological parameters and clinical outcome, and to determine the predictive and prognostic value of these transport proteins in patients with ovarian cancer.Methods: Tumor samples from 111 chemonaive patients with epithelial ovarian cancer who underwent primary surgery from 2006 to 2010 were immunohistochemically stained for LRP, Pgp, MRP1, MRP3, and MRP5 expressions.Results: MRP1 expression was greater among patients with late disease than among patients with early stage ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) I + II, 71.6% (confidence interval, 60-100); FIGO III + IV, 83.6% (confidence interval, 100-100); P = 0.03]. The histological subtype correlated with the expressions of LRP, Pgp, MRP1, and MRP3. Relapse of disease during the next 24 months occurred more often among patients with higher Pgp and MRP1 than among patients with lower Pgp and MRP1 expressions. FIGO stage, histological type, debulking efficiency, strong Pgp expression, and strong MRP1 expression correlated significantly with shorter progression-free survival (log-rank test, P = 0.001, P = 0.004, P = 0.001, P = 0.051, and P = 0.046, respectively). FIGO stage, histological type, debulking efficiency, and strong MRP1 expression correlated with poor patient survival (log-rank test, P = 0.001, P = 0.042, P = 0.005, and P = 0.018, respectively).Conclusions: Pgp and MRP1 expressions were clinically significant in patients with ovarian cancer. Pgp and MRP1 may be reliable, independent predictive and prognostic factors regarding the clinical outcome of ovarian cancer. MRP3 is less important as a predictive and prognostic factor than MRP1 expression. MRP5 and LRP expressions were not applicable prognostic parameters regarding ovarian cancer.
OBJECTIVE:To analyze hypersensitivity reactions to carboplatin and paclitaxel in patients treated with systemic administration of chemotherapy (carboplatin and/or paclitaxel).DESIGN:Retrospective study.SETTING:Department of Obstetrics and Gynecology, Charles University in Prague, Faculty of Medicine and University Hospital Hradec Kralove.METHODS:One hundred-forty patients treated with systemic administration of chemotherapy were enrolled to our study between years 2008 and 2012. The presence and the grade [grade (G) 1-5; 1 = moderate, 5 = death] of hypersensitivity reactions (HSRs) were evaluated, as well as the influence of some clinical parameters on development of HSR.RESULTS:In total 29 HSRs in 21 patients were analyzed. To carboplatin were reported 19 (66%) HSRs: 13 (45%) HSRs of G1-G3 and 6 (21%) HSRs of G4. To paclitaxel were reported 10 (34%) HSRs: 9 (31%) HSRs of G1-G3 and 1 (3%) HSR of G4. The number of administered cycles of carboplatin to develop G1-G4 resp. G1-G3 HSR was higher in comparison with number of cycles to develop HSR of the same grade to paclitaxel(p = 0.001, resp. p = 0.01).CONCLUSION:HSR to carboplatin is unlike paclitaxel affected by the number of administered cycles. This fact should be included in the clinical management of patients treated with intravenous chemotherapy using carboplatin.
OBJECTIVE:To analyze differences between primary fallopian tube cancer and ovarian cancer.DESIGN:Overview study.SETTING:Department of Obstetrics and Gynecology, The Fingerland Department of Pathology, Department of Oncology and Radiotherapy, Faculty of Medicine and University Hospital Hradec Kralove.METHODS:Overview study focused on analysis of data of primary fallopian tube cancer.CONCLUSION:The incidence of primary fallopian tube cancer was thought to be very low in the past but it is very difficult to assess the primary origin in the case of advanced disease (ovary versus fallopian tube). Tumorogenic potential of endosalpinx in relation to epithelial tumours is much more bigger. According to the current knowledge, the vast majority of high-grade serous carcinomas of the "ovary" in fact arise in the mucosa of fimbrial portion of fallopian tube.
OBJECTIVE:To compare plasma VEGF (vascular endothelial growth factor) levels in ovarian cancer patients, in patients with benign ovarian tumors and healthy women.DESIGN:Prospective study.SETTING:Department of Gynecology and Obstetrics, Medical Faculty Charles University, Prague and University Hospital, Hradec Králové. Department of Immunology and Alergology, Medical Faculty Charles University, Prague and University Hospital, Hradec Králové.METHODS:VEGF was estimated by ELISA (R&D Systems).RESULTS:We found that plasma VEGF levels were associated with the International Federation of Gynecology and Obstetrics (FIGO) stage (FIGO I+II, n=8) Med = 425,53 pg/ml (range 142,30-982,40 pg/ml), (FIGO III+IV, n=29) Med = 941,48 pg/ml (range202,10-2857,80 pg/ml) (p=0,03). Patients with primary ovarian cancer (n=37) had a significantly higher plasma VEGF level Med = 829,93 pg/ml (range142,30-2857,80 pg/ml), compared with patients with benign ovarian tumors (n=15) Med = 426,28 pg/ml (range 32,00-922,20 pg/ml) and healthy women (n=21) Med = 283,13 pg/ml (range 80,50-735,20 pg/ml) (p=0,0003). VEGF levels were lower in plasma (n=79) Med = 575,49 pg/ml (range 55,80-2185,00 pg/ml) compared with VEGF levels in ascitic fluid (n=37) Med = 745,74 pg/ml (range 142,30-2185,00 pg/ml) (p=0,04) in ovarian cancer patients.CONCLUSION:Plasma VEGF assay before primary treatment and the changes during the other treatment should contribute to better understanding of angiogenesis in ovarian cancer patients. Plasma VEGF correlates with the stage of primary ovarian cancer.
BACKGROUNDTo evaluate the correlation of resistance proteins LRP (Lung Resistance Protein), Pgp (P-glycoprotein), MRP (Multidrug Resistance-Associated Protein), MRP3 a MRP5 with stage, grade and histological type. To asses correlation of these resistance proteins with drug resistance/drug sensitivity in vitro by means of the MTT assay in ovarian cancer patients. To find the clinical outcome of these data.PATIENTS AND METHODS64 women with epithelial ovarian cancer who underwent primary surgery in 2006-2010 had specimens stained with immunohistochemistry for LRP, MRP, MRP3, MRP5 and Pgp and MTT assay (MTT-(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide).RESULTSPatients with late ovarian cancer had a higher Pgp, MRP, MRP3 and MRP5 level compared to ovarian cancer patients with early stage ovarian cancer. No correlation of resistance proteins with grading was found. Patients with high Pgp and MRP expression had significantly shorter progression-free survival. Patients with drug resistance in vitro by means of the MTT assay had higher Pgp and MRP expression.CONCLUSIONP-glycoprotein and MRP may be useful predictor for outcome of primary chemotherapy in patients with ovarian cancer.
OBJECTIVE:To assay correlation between primary resistance/sensitivity in vitro by MTT test in solid tumor and ascitic fluid and clininical outcome in ovarian cancer patients.DESIGN:Prospective study.SETTING:Department of Gynecology and Obstetrics, Medical Faculty Charles University, Prague and University Hospital, Hradec Králové.METHODS:MTT - (3-(4,5 - Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) chemosensitivity assay was performed in 45 samples of ovarian cancer tissue and 26 samples of ascitic fluid in ovarian cancer patients. We studied the in vitro drug resistance profiles of ovarian cancer specimens exposed to cisplatin, carboplatin, paclitaxel, topotecan, gemcitabin, etoposid.RESULTS:The highest incidence of primary drug resistance in vitro had gemcitabin and carboplatin and the lowest incidence of primary drug resistance had cisplatin and topotecan. Cisplatin had lower incidence of primary drug resistance in vitro than carboplatin. Grade and stage of epithelial ovarian cancer did not correlate to the primary drug resistance/sensitivity in vitro in ovarian cancer patients. The histological subtype of epithelial ovarian cancer correlated to the resistance and sensitivity to chemotherapeutic agents in vitro. Ovarian cancer patients with primary drug resistance to paclitaxel and carboplatin in vitro had more complications during primary chemotherapy, shorter progression free interval and worse prognosis of the disease.CONCLUSION:The lowest incidence of primary drug resistance in vitro had cisplatin. Ovarian cancer patients with in vitro resistance to paclitaxel and carboplatin had significantly higher risk for progression of disease when treated with standard platinum-paclitaxel based regimens. The primary resistance/sensitivity assay would contribute to the targeted treatment and better prognosis of ovarian cancer patients.
OBJECTIVE:To assay resistance/sensitivity by MTT test in solid tumor or ascitic fluid in ovarian cancer patients.DESIGN:Prospective study.SETTING:Department of Gynecology and Obstetrics, Medical Faculty Charles University, Prague and University Hospital, Hradec Králové.METHODS:MTT - (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) chemosensitivity assay was performed in 32 samples of ovarian cancer tissue and 26 samples of ascitic fluid in ovarian cancer patients. We studied the in vitro drug resistance profiles of ovarian cancer specimens exposed to cisplatin, carboplatin, paclitaxel, topotecan, gemcitabin, etoposid.RESULTS:The highest frequency of resistance in vitro occured for etoposid, gemcitabin and paclitaxel and the most effective chemotherapeutical agents in vitro were cisplatinum and topotecan. Cisplatin had the lowest incidence of drug resistance in vitro than carboplatin.CONCLUSION:Resistance/sensitivity assay would improve the treatment and prognosis of ovarian cancer patients.
OBJECTIVE:To describe chemoresistance and chemosensitivity of two ovarian cancer patients and influence on their medical outcome.SETTINGS:Department of Obstetrics and Gynecology, Medical Faculty Charles University Prague and University Hospital, Hradec Králové.SUBJECT AND METHOD:A case report of two ovarian cancer patients with defined chemoresistance/chemosensitivity of their tumors. We used WST-MTT-1 test for the assessment of chemoresistance/chemosensitivity.CONCLUSION:The chemoresistance/chemosensitivity assay would improve the treatment and prognosis of ovarian cancer patients.