Effect of the treatment stage on the serum levels of selected cytokines and antioxidant enzymes in patients with tumors of the reproductive organs.

OBJECTIVE: Chronic inflammation along with concomitant oxidative stress contributes to an increased risk of cancer development. The aim of this study was to analyze selected cytokines and antioxidant enzymes in patients with ovarian and endometrial cancers, taking into account the stage of oncological treatment. PATIENTS AND METHODS: The study sample included 52 female patients with advanced endometrial cancer (n = 26.50%) and ovarian cancer (n = 26.50%), undergoing chemotherapy. Long-term observation at four time points was used in the subjects. Each of the women was blood sampled several times (before surgery, and then before the first, third, and sixth cycle of chemotherapy) in order to determine serum levels of pro- and anti-inflammatory cytokines and antioxidant enzymes. RESULTS: The levels of catalase (CAT), glutathione reductase (GR), interleukin (IL)-10, IL-1α, IL-4 differed significantly depending on the stage of therapy and the type of cancer. The serum levels of IL-4 and IL-10 in patients with ovarian cancer were statistically significantly higher than those observed in patients with endometrial cancer. The activity of the tested antioxidant enzymes varied depending on the chemotherapy cycle. Their highest activity in most cases was observed before the third cycle of chemotherapy, and it decreased before the sixth cycle, irrespective of the type of cancer. CONCLUSIONS: In the studied group of patients with ovarian and endometrial cancer, the applied chemotherapy significantly changed the concentration and activity of some interleukins and antioxidant enzymes. The type of tumor determined the levels of IL-4 and IL-10 before the treatment. Evaluation of inflammatory parameters and oxidative stress in women with cancer of the reproductive organ may help to understand physiological changes resulting from the applied therapy.

The impact of an expanded genetic testing program and selective oophorectomy on the incidence of ovarian cancer in West Pomerania.

The aim of the study was to evaluate the impact of a regional population-based genetic testing program on the incidence of ovarian cancer in West Pomerania. Between 1999 and 2010, a total of 37,552 women ages 35 to 70 were tested for three BRCA1 founder mutations at the outpatient genetics clinic of the Pomeranian Medical University in Szczecin, Poland. A total of 641 women were found to carry a mutation (1.7%) and of these, 220 had a prophylactic oophorectomy (34.3%). A total of 12 women had an occult cancer diagnosed at the time of prophylactic oophorectomy (5.5%). We estimate that 26 more ovarian cancers would have been diagnosed by January 2015 in the absence of these oophorectomies and that an additional 25 cancers will be prevented in the future (total 51). During this period, 1611 ovarian cancers were diagnosed in the region; therefore we estimate that approximately 1.6% of ovarian cancers were prevented between 1999 and 2015 by our genetic testing program. We conclude that the prophylactic oophorectomies performed between 1999 and 2010 as a result of widespread BRCA1 mutation testing have reduced the incidence of ovarian cancer in Pomerania by a small amount (about 1.6%), and that the impact of genetic testing will increase in the coming years.

Human epididymal protein 4 (HE4) is a novel biomarker and a promising prognostic factor in ovarian cancer patients.

PURPOSE OF INVESTIGATION: The aim of this work was to compare serum concentrations of HE4 in patients with benign and malignant epithelial tumors and to determine the association of preoperative concentrations of HE4 with some clinicopathologic factors. METHODS: We enrolled 94 patients, including 39 females with freshly diagnosed ovarian cancer. HE4 concentrations were measured with ELISA HE4 EIA assay from Fujirebio Diagnostics. RESULTS: Serum concentrations of HE4 differed significantly in patients with ovarian cancer (324.1 pM) compared with benign epithelial tumors (26.1 pM; p < 000.1). There was also a significant difference between HE4 concentrations at diagnosis of ovarian cancer (324.1 pM) and in patients with complete clinical remission (23.3 pM; p < 0.0001). Patients with poorly differentiated tumors had significantly higher concentrations of HE4. Preoperative HE4 levels were higher in patients in whom relapse was noted and who died before the end of the two-year follow-up period. CONCLUSION: On the basis of these findings and reports in the literature it appears likely that HE4 can complement CA125 in the monitoring of therapy in ovarian cancer and may also serve for prognostication.

Favorable effects of long-term therapy with gonadoliberin analogues in three patients with advanced and recurrent ovarian cancer.

BACKGROUND: Numerous scientific reports indicate a high possibility of gonadotrophin involvement in ovarian cancer neoplasia. CASE PRESENTATION: In a 49-year-old patient with recurrent ovarian cancer, a present survival of ten years has been achieved. She has been using GnRH analogues for nine years. A 32-year-old patient with a primary highly advanced ovarian cancer received standard therapy and additional implants with GnRH analogues as consolidation therapy for 20 months. Overall survival is 14 years. In a 56-year-old patient with advanced ovarian cancer GnRH analogues were used as consolidation therapy for seven years, achieving seven years of a complete clinical remission and nine and a half years of survival up to now. CONCLUSION: It seems that gonadoliberin analogues should find their place in ovarian cancer therapy.

Serum YKL-40 levels in patients with ovarian cancer and women with BRCA1 gene mutation--comparison to CA 125 antigen.

PURPOSE OF INVESTIGATION: Our work was undertaken to determine the usefulness ofYKL-40 as a tumor marker in patients with ovarian cancer and women with BRCA 1 gene mutations. METHODS: Our study population consisted of 111 patients. They were divided into five study groups: I--newly diagnosed ovarian caner, II--recurrence of ovarian cancer, III--complete remission, IV--benign epithelial tumors and V--patients with BRCA 1 gene mutations. YKL-40 and CA 125 were determined in patient sera. RESULTS: YKL-40 in newly diagnosed ovarian cancer patients was significantly higher (181.17 n/ml) than in patients with BRCA 1 gene mutation (97.74 ng/ml, p < 0.01), women with benign epithelial cancer (57.19 ng/ml, p < 0.005) and patients with ovarian cancer at the time of complete remission (58.12 ng/ml, p < 0.005). Taking 124 ng/ml as a cut-off value for YKL-40 (95th percentile for healthly women) we observed higher levels in 50% of patients from group I and in 38% from group II. CONCLUSIONS: YKL-40 appears to demonstrate no advantage over CA 125 as a biomarker of ovarian cancer, particularly in women with early-stage tumors. More research is needed on carriers of the BRCA 1 gene muation in view of the elevated YKL-40 concentrations in this group.

Concentrations of follicle stimulating hormone are increased in ovarian tumor fluid: implications for the management of ovarian cancer.

PURPOSE OF INVESTIGATION: Significant progress has been made in recent years in the understanding of the mechanisms postulated by the gonadotropin theory of ovarian carcinogenesis. In the present study we compare FSH concentrations between serum and fluid from cysts or the rectouterine pouch of patients with epithelial tumors and non-neoplastic lesions. METHODS: We enrolled 277 patients. They were divided into five groups: I (n = 44)--ovarian cancer patients, II (n = 16)--borderline tumors, III (n = 40)--benign epithelial cystadenomas, IV (n = 137)--non-neoplastic lesions and V (n = 22)--admitted for "second-look" laparoscopy. RESULTS: There were any significant differences between FSH concentrations in serum and tumor fluid in patients with ovarian cancer (36.46 vs 28.11 mIU/ml) and borderline epithelial tumors (31.5 vs 22.7 mIU/ml). For benign cystadenomas the respective concentrations were 28.96 mIU/ml in serum and 6.93 mIU/ml in tumor fluid in these groups p < 0.0000001. The same highly significant differences were found in non-neoplastic lesions (24.97 vs 4.77 mIU/ml), p < 0.0000001. Patients who underwent "second-look" laparoscopy demonstrated significant differences (p < 0.05) as FSH concentration in serum and peritoneal fluid when neoplastic cells were not disclosed, but the difference was not significant (p = 0.752) when fluid from the rectouterine pouch was positive for carcinoma cells. CONCLUSIONS: The results of our study can reflect an ineffective tumor: blood barrier and easy diffusion of gonadotropins into the tumor tissue. Local reduction of FSH levels through administration of GnRH analogs may in some clinical situations produce clear therapeutic benefits for the management of ovarian malignancies.

Serum adiponectin in relation to endometrial cancer and endometrial hyperplasia with atypia in obese women.

OBJECTIVES: The aim of this work was to compare concentrations of adiponectin in the serum of obese women with endometrial cancer, endometrial hyperplasia with atypia, and normal endometrium. METHODS: We enrolled 105 obese women treated at the Department of Gynecological Surgery and Oncology of Adults and Adolescents. The patients were allocated to groups depending on the histological diagnosis (R - endometrial cancer, P - polyps, K - normal endometrium). We subdivided group R depending on the stage and grade of cancer. RESULTS: Significantly lower concentrations of adiponectin were found in patients with endometrial cancer (mean 15.28 microg/ml) as compared with polyps (29.94 microg/ml, p < 0.001) or normal endometrium (22.7 microg/ml, p < 0.05). Stage of cancer had no significant effect on the adiponectin level. When cancer grade was compared, lower levels of adiponectin were observed in patients with G3 (12.86 microg/ml) than G1 (19.04 microg/ml, p < 0.05). CONCLUSION: Reduced levels of adiponectin may represent an independent risk factor for endometrial cancer.

BRCA1 mutation, leptin and estrogen levels in breast cancer patients.

Pre- and postmenopausal patients with breast cancer were screened for mutation of the BRCAI gene and estrogens and leptin levels were measured. In postmenopausal BRCA1 mutation carriers, leptin levels were significantly lower and correlated with the body mass index (BMI). No significant difference in leptin levels was revealed between pre- and postmenopausal patients. Our findings suggest the existence of an alternative mechanism responsible for carcinogenesis in breast cancer patients with a genetic background.

Vascular endothelial growth factor (VEGF) levels and mutation of the BRCA1 gene in breast cancer patients.

The aim of the study was to compare VEGF serum levels in breast cancer patients with and without BRCA1 gene mutation. We enrolled 80 patients, 22 premenopausal and 58 postmenopausal. We found statistically significant lower levels of VEGF in patients with BRCA1 gene mutation as compared with breast cancer patients without this mutation.

FSH and LH serum/tumor fluid ratios and malignant tumors of the ovary.

The aim of this work was to compare mean concentrations of gonadotropins in serum and fluid from malignant and benign ovarian tumors. We enrolled 126 patients diagnosed with malignant epithelial tumors (n=40), borderline epithelial tumors (n=14), benign cystadenomas (n=28) and simple cysts (n=44) of the ovary. Premenopausal and postmenopausal subgroups were formed in each group. The concentration of FSH and LH was measured in serum and tumor fluid and the serum/tumor fluid ratio was calculated. The results in each group were compared and the sensitivity, specificity, positive and negative predictive values were determined. Mean concentrations of both gonadotropins in ovarian cancer fluid were significantly higher than in the remaining groups (P ranged from <0.005 to <0.0001). Mean serum/fluid ratios were lowest in ovarian cancer (FSH=2.91, LH=4.19). Our findings support the hypothesis that gonadotropins are involved in ovarian carcinogenesis and suggest that gonadotropin serum/tumor fluid ratios could be of value in the differential diagnosis of functional and organic cysts of the ovary.

P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens.

BACKGROUND: The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups. RESULTS: High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001). CONCLUSIONS: We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.

GnRH analogues as an adjuvant therapy for ovarian cancer patients.

OBJECTIVES: Lowering gonadotropin levels with gonadotropin-releasing hormone (GnRH) analogues in patients with ovarian cancer remains open to debate. The aim of this study was to assess the results of treatment in stage III and stage IV ovarian cancer patients who had surgery supplemented with chemotherapy, radiotherapy, and GnRH analogues. Gonadotropin levels were monitored during treatment. METHODS: The study group comprised 69 patients aged 27-70 years, stratified according to the type of treatment. The overall disease-free, 5-year survival rates and the frequency of remissions were analyzed. Hormonal tests [follicle-stimulating hormone (FSH) and luteinizing hormone (LH)] were performed in 58 patients. Associations were checked between gonadotropin levels, clinical findings, and survival. The results were statistically compared. RESULTS: Statistically significant differences were noted when chemotherapy was supplemented with GnRH analogues and/or radiotherapy. Administration of GnRH analogues resulted in significantly lower levels of LH than of FSH. Levels of FSH were significantly lower in patients surviving at least 5 years or in complete remission at the time of this study. CONCLUSIONS: Combined therapy can produce favorable results in late-stage ovarian cancer, and GnRH analogues have an important role in treatment strategy.

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen.

In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatin-based chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB-IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P=0.005) or the only (in FIGO IIIC, P=0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(-) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P=0.047) and by BCL2 expression in the TP53(-) group (P=0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P=0.049); its loss was found with advancing FIGO stage (P=0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

[Adolescent endometriosis]. / Endometrioza u dziewczat.

DESIGN: The aim of our study was estimation of frequency of occurrence endometriosis at girls operated from different indications, research of predisposing factors and estimation of selected biophysical parameters. MATERIAL AND METHODS: Material determined 14 of patients in 13 to 21 years old of life operated on account of endometriosis of sexual organs in our Clinic in years 1996-1999. We study the frequency of occurrence of illness, analysis of perceptible clinical reasons, clinical stage of disease using ASF classification. It was analysed according to gynaecological age of girls, periodical complaints, cystical changes in ultrasound investigation. In serum of blood the level of CA125 was analysed with ready sets of firm Abbott. Congenital malformations were classed according to Buttram classification. CONCLUSIONS: On base obtained of results one ascertained, that protracted pain in pelvis not responding to analgesic and antiphlogistic treatment is indication to complex diagnostics with regard of laparoscopy making possible diagnosis of endometriosis. One ascertained also, that sensibilizing of doctors on predisposing factors to formations of endometriosis (congenital malformations, intrauterine device) can contribute to preventive activities.

[Surgical treatment in child gynecology. Germ cell tumors of the ovary in girls]. / Leczenie operacyjne w ginekologii dziewczecej i dzieciecej. Nowotwory germinalne jajnika u dziewczat.

The authors presented 50 girls with germ cell tumours of the ovary. 9/50 (4.5%) were malignant germ-cell tumours. There were 5 patients with pure dysgerminomas, 1 with endotermal simus tumor, 3 with immature teratomas, 3 with gonadoblastoma, 38 with mature teratoma. Kariotype 46XY was present in patients. Authors prefer fertility sparing operative treatment. Primary postoperative therapy in malignant tumors was chemotherapy or radiotherapy. Authors recommend sift out ultrasonographic investigation. Girls should be individually considered for appropriate ovarian surgical procedures. The operative treatment should be as conservative as possible. Absence of follicle apparatus in the gonads require determination of levels of gonadotropin and kariotype.

[The comparison of CA-125 and CEA levels in serum and ovarian cyst fluid in girls and young women]. / Porównanie poziomu markerów nowotworowych CEA i CA-125 w surowicy krwi oraz w plynie z torbieli jajnika u dziewczat i mlodych kobiet.

OBJECTIVES: The aim of the study was to compare the CA-125 and CEA levels in serum and ovarian cyst fluid. MATERIALS AND METHODS: Concentration of the CA-125 and CEA were measured at 12 girls and young women with benign, low malignant potential and functional cysts hospitalized in our teaching department. Concentrations were measured using immunoenzymatic method. RESULTS: We did not observe any difference in serum levels of CA-125 and CEA between neoplastic and functional cysts. On the contrary we found very high levels of the markers in the neoplastic cyst fluid in comparison with the functional ovarian cyst fluid. CONCLUSION: It seems that high levels of the CA-125 and CEA in neoplastic cyst fluid in comparison with functional may be useful in differential diagnosis.

[The levels of selected hormones in serum and ovarian cyst fluid in girls and young women]. / Zachowanie sie wybranych hormonów w surowicy krwi i plynie z torbieli jajnika u dziewczat i mlodych kobiet.

OBJECTIVES: The aim of the study was to determinate levels of the FSH, LH and E2 in serum and ovarian cyst fluid in neoplastic tumors (7 benign, 1 of low malignant potential) and functional cysts. MATERIAL AND METHODS: We measured the concentrations of the FSH, LH and E2 at 12 girls and young women hospitalized in our teaching department using immunoenzymatic method. RESULTS: We found higher levels of gonadotropins in serum and particular in ovarian cyst fluid at neoplastic tumors in comparison with functional cysts. There were also high levels of estradiol and low of gonadotropins in functional ovarian cyst fluid. CONCLUSION: The differences of FSH, LH and E2 levels in ovarian cyst fluid in neoplastic and functional cyst have cognitive character and need more investigations.

[Laparoscopy in the diagnosis and treatment of pathology of sexual organs in girls]. / Laparoskopia w diagnostyce i leczeniu patologii narzadu plciowego u dziewczat.

DESIGN: The aim of our study was a clinical analysis of laparoscopies in girls which were performed in the Clinic of Gynaecological Surgery. MATERIAL AND METHODS: Laparoscopic procedures were carried out between 1996-1998. Patients were divided in to three groups: aged under 15, between 15-19 and over 19. 44% of patients from the youngest group had laparotomy. 43.8% of laparoscopic interventions were in aged group 20-24. CONCLUSION: Laparoscopy is very good diagnostic method in gynaecological diseases. It gave enabled operative treatment in 40-43.8% girls.