The impact of disease distribution on survival in patients with stage III epithelial ovarian cancer cytoreduced to microscopic residual: a Gynecologic Oncology Group study

Objective

To assess the survival impact of initial disease distribution on patients with stage III epithelial ovarian cancer (EOC) cytoreduced to microscopic residual.

Methods

We reviewed data from 417 stage III EOC patients cytoreduced to microscopic disease and given adjuvant intravenous platinum/paclitaxel on one of three randomized Gynecologic Oncology Group (GOG) trials. We subdivided patients into three groups based on preoperative disease burden: (1) minimal disease (MD) defined by pelvic tumor and retroperitoneal metastasis (2) abdominal peritoneal disease (APD) with disease limited to the pelvis, retroperitoneum, lower abdomen and omentum; and (3) upper abdominal disease (UAD) with disease affecting the diaphragm, spleen, liver or pancreas. We assessed the survival impact of potential prognostic factors, focusing on initial disease distribution using a proportional hazards model and estimated Kaplan-Meier survival curves.

Results

The study groups had similar clinicopathologic characteristics. Median overall survival (OS) was not reached in MD patients compared to 80 and 56 months in the APD and UAD groups (P < 0.05). The five-year survival percentages for MD, APD, and UAD were 67%, 63%, and 45%. In multivariate analysis, the UAD group had a significantly worse prognosis than MD and APD both individually and combined (Progression Free Survival (PFS) Hazards Ratio (HR) 1.44; P = 0.008 and OS HR 1.77; P = 0.0004 compared to MD + APD).

Conclusion

Stage III EOC patients with initial disease in the upper abdomen have a worse prognosis despite cytoreductive surgery to microscopic residual implying that factors beyond cytoreductive effort are important in predicting survival.     

Expression of 67-kDa laminin receptor was associated with tumor progression and poor prognosis in epithelial ovarian cancer

Objective

67-kDa laminin receptor (67LR) has been identified as a prognostic biomarker for a variety of human cancers. We investigated the clinical significance of 67LR expression and its functional role in epithelial ovarian cancer (EOC).

Methods

67LR expression was evaluated by immunohistochemistry in 62 patients with EOC. We assessed the correlation of 67LR expression with clinical characteristics. In vitro experiment was performed for 67LR with inhibition using siRNA to evaluate its role in cell survival, apoptosis, and invasion in EOC cells.

Results

67LR was predominantly expressed on the cell membrane in the majority of EOC samples (45/62, 73%). 67LR expression was significantly correlated with advanced stage (P = 0.001). Patients with 67LR expression had shorter progression-free survival among all the patients (P = 0.010) and in particular among patients with advanced stages (P = 0.046). When 67LR expression was inhibited by siRNA in EOC cells (HeyA8 and A2780), there was a significant decrease of cell proliferation and invasion as well as increase of apoptosis.

Conclusion

These findings suggest that 67LR expression may play an important role in tumor progression into advanced stage with poor prognosis in EOC and down-regulation of 67LR on tumor cells may be a therapeutic target in those patients.     

Micropapillary pattern in serous borderline ovarian tumors: does it matter?

Objective

To evaluate the clinical and prognostic impact of micropapillary pattern in patients with serous borderline ovarian tumors (SBOT).

Methods

We retrospectively assessed 130 consecutive patients with typical (n = 97, 74.6%) or micropapillary (n = 33, 25.4%) SBOT. Clinicopathologic factors and outcomes were compared between these two groups.

Results

There were no significant between-group differences in age, menopausal status, parity, body mass index, cancer antigen 125 concentration, tumor size, tumor rupture, positive cytology, ovarian surface involvement, retrieved lymph nodes, use of laparoscopy, fertility-sparing and ovary-sparing procedures, complete staging and restaging, and adjuvant chemotherapy. However, the incidences of advanced stage (II-III) tumors (10.3% vs 36.4%, P = 0.001), microinvasion (2.1% vs 15.2%, P = 0.012), peritoneal implants (8.3% vs 33.4%, P < 0.001), and lymph node involvement (0% vs 21.2%, P < 0.001) were significantly higher in patients with micropapillary than with typical SBOT. Five patients with typical (5.2%) and three with micropapillary (9.1%) SBOT had recurrent disease (P = 0.418), and one patient (3%) in micropapillary SBOT group died due to the disease (P = 0.254). The 5-year disease-free survival (DFS) rates for patients with typical and micropapillary SBOT were 96% and 86%, respectively (P = 0.148). All three patients with micropapillary SBOT who had recurrence had peritoneal implants (one noninvasive and two invasive). Multivariate analysis showed that peritoneal implant was the only significant factor related to DFS (P = 0.002).

Conclusions

Because micropapillary SBOT was significantly associated with peritoneal implants, especially invasive implants, and lymph node involvement, complete staging procedures, including lymph node dissection, are recommended. However, micropapillary SBOT itself was not significantly associated with DFS. Peritoneal implant was the only factor independently associated with tumor recurrence.     

Polymorphisms in the CASP8 gene and the risk of epithelial ovarian cancer

Objective

The CASP8 gene plays a central role in the apoptotic pathway and is therefore a plausible cancer susceptibility gene. However, the precise role of the CASP8 gene in epithelial ovarian cancer carcinogenesis is unclear. Therefore, we analyzed the correlation between single nucleotide polymorphisms (SNPs) and haplotypes in CASP8 and the risk and clinical characteristics of epithelial ovarian cancer (EOC) in the Chinese population.

Subjects and methods

Eight tag SNPs were identified using the MassARRAY system to genotype 37 genetic polymorphisms around and in the CASP8 gene in 100 unrelated, healthy females. Then, a case-control study of 218 EOC patients and 285 controls who were matched on residence, age and race was conducted using these 8 tag SNPs.

Results

The risk of developing EOC was significantly decreased in association with CASP8 rs3834129 ins > del (odds ratio (OR)_del/del = 0.129, 95% confidence interval (95% CI): 0.038-0.439; OR_ins/del = 0.769, 95% CI, 0.534-1.108), rs3769827 T > C (OR_C/C = 0.187, 95% CI: 0.070-0.500; OR_T/C = 0.729, 95% CI: 0.505-1.052), rs6704688 C > T (OR_T/T = 0.344, 95% CI, 0.168-0.707; OR_C/T = 0.802, 95% CI, 0.552-1.166), and with the del-C-T haplotype of these 3 SNPs (OR = 0.615, 95% CI: 0.453-0.8363). Moreover, a notably later onset was significantly associated with the rs3834129 ins/del + del/del and the rs3769827 T/C + C/C genotypes (p < 0.0001).

Conclusions

Genetic variants of the CASP8 gene protect against EOC carcinogenesis and delay the age of EOC onset. Furthermore, these protective effects may be due to the dysfunctional expression of caspase-8 caused by the − 652 6 N del variant in the promoter.     

Trends in therapy and survival of advanced stage epithelial ovarian cancer patients in the Netherlands

Objective

The aim of this study was to describe trends in survival and therapy in advanced stage epithelial ovarian cancer (EOC) in the Netherlands and to determine if changes in therapy affected survival.

Methods

All EOC patients diagnosed in the Netherlands during 1989-2009 were selected from the Netherlands Cancer Registry. Differences in treatment over time were tested by the Cochran-Armitage trend test. Multivariable relative survival analyses were performed to test whether changes in treatment are associated with survival.

Results

23,399 EOC patients were diagnosed, of whom 15,892 (67.9%) in advanced stage (stage ≥ 2b). In advanced stage patients, the proportion receiving (neo-)adjuvant chemotherapy and optimal debulking (residuals < 1 cm) increased over time in all age groups. In elderly patients (≥ 75 years) a stable proportion (approximately 28%) did not receive any treatment. Five-year relative survival in advanced stage patients increased from 18% in 1989-1993 to 28% in 2004-2009. In the multivariable model survival improved over time (relative excess risk (RER) of 2004-2009 was 0.71, 95% CI 0.67-0.75 compared to 1989-1993). This RER attenuated to 0.85 (95% CI 0.80-0.90) and 0.91 (95% CI 0.83-0.99) with inclusion of treatment variables in the model (surgery with chemotherapy or optimal surgery with chemotherapy, respectively). This suggests that the improvement was mainly, although not entirely, caused by changes in treatment.

Conclusion

Treatment in advanced stage EOC patients in the Netherlands improved over the last two decades; more patients received (neo)adjuvant chemotherapy and underwent optimal debulking surgery. Changes in treatment led to partial improvement of survival in EOC patients.     

Oral misoprostol versus intracervical prostaglandin E2 gel for active management of premature rupture of membranes at term

Objective

To compare the efficacy and safety of oral misoprostol with intracervical prostaglandin E2 (PGE2) gel for the active management of premature rupture of membranes (PROM) at term.

Methods

Women with pregnancies between 37 and 42 weeks presenting with PROM at term and a Bishop score of 5 or less were randomly assigned to receive either a 4-hourly oral dose of 50 µg of misoprostol up to a maximum of 3 doses or 2 applications of intracervical PGE2 gel at a 6-hour interval. Oxytocin was given if labor had not started after 12 hours.

Results

Twenty women in the misoprostol group (n = 31) delivered within 12 hours compared with 5 in the PGE2 group (n = 30) (P < 0.001). The induction-to-delivery interval in the misoprostol group was shorter than in the PGE2 gel group (615 min vs 1070 min; P < 0.001). The mode of delivery was comparable between the 2 groups (P = 0.821). Abnormalities in uterine contractions and neonatal outcomes were also comparable. The requirement for oxytocin was lower and patient satisfaction was better in the misoprostol group.

Conclusion

Oral misoprostol is a safe and efficacious alternative to intracervical PGE2 gel in the active management of PROM at term.     

Clinico-pathologic comparison of type II endometrial cancers based on tamoxifen exposure

Objective

To compare clinico-pathologic variables and protein expression of potential regulatory components in patients who develop type II endometrial cancer with and without antecedent tamoxifen.

Methods

Clinico-pathologic variables were compared for all surgically staged patients (2000-2008) with grade 3 endometrioid, papillary serous, clear cell, and carcinosarcoma of the uterus based on tamoxifen exposure [Tam (+) vs. Tam (−)]. Overall survival was analyzed using a multivariable Cox regression model and Kaplan-Meier estimates. Protein expression of ERα, PR, mTOR, p-mTOR, IGF-1R, EGFR, VEGF and HER-2/neu was compared by immunohistochemistry using a semiquantitative scoring system.

Results

Of 115 patients with high grade endometrial cancers, 15 received tamoxifen. These patients were older at diagnosis than Tam (−) patients. A higher percentage of Tam (+) patients had carcinosarcoma compared to Tam (−) patients (60% vs. 30%, P = 0.038). Overall survival for Tam (+) patients was shorter than Tam (−) patients (16.6 vs. 32.2 months, P = 0.004). The hazard ratio for death for Tam (+) patients was 2.53 (P = 0.014), controlling for age and stage. Intensity and extent of staining were similar for ERα, PR, VEGF, EGFR, p-mTOR and HER-2/neu. The average expression score for IGF-1R and mTOR in the Tam (+) group was significantly higher than the Tam (−) group: 10.3 vs 7.0, P = 0.001 and 6.0 vs 3.1, P = 0.029, respectively.

Conclusion

There are differences in the biology of type II endometrial cancers that develop in women with prior tamoxifen exposure. Tamoxifen associated cancers show higher expression of IGF-1R and mTOR, which should be further investigated.     

Goserelin versus leuprolide before hysterectomy for uterine fibroids

Objective

To compare goserelin and leuprolide given before hysterectomy for symptomatic large fibroid uteri.

Methods

A randomized study of 66 premenopausal women with fibroid uteri at least 14 weeks of gestation in a gravid uterus. Women were randomized to receive either subcutaneous depot 3.6 mg goserelin or 3.75 mg leuprolide every 4 weeks for a total of 3 doses. Hysterectomy was performed within 1 month of the last dose.

Results

A total of 34 women randomized to the goserelin group and 31 women to the leuprolide group were available for analysis. Preoperative hemoglobin level (P = 0.89), operative blood loss (P = 0.72), and operating time (P = 0.39) were not different between the 2 groups. Postoperative hemoglobin was higher in the leuprolide group (P = 0.003), but blood transfusion requirement was not different between the groups (P = 1.0). Other outcomes and side effects of the drugs were similar.

Conclusions

Goserelin and leuprolide administered before hysterectomy for uterine fibroids have similar perioperative outcomes.     

Should stage IIIC ovarian cancer be further stratified by intraperitoneal vs. retroperitoneal only disease?: a Gynecologic Oncology Group study

Objective

To examine whether clinical outcomes varied with intraperitoneal (IP) and/or retroperitoneal (RP) involvement in stage IIIC epithelial ovarian cancer (EOC) patients with microscopic residual disease after cytoreduction.

Methods

Retrospective review was performed for EOC patients enrolled in Gynecologic Oncology Group (GOG)-182 who underwent primary cytoreduction to microscopic residual disease. Patients were divided into 3 groups: stage IIIC by lymphadenopathy with < 2 cm IP spread (RP); > 2 cm IP spread and negative nodes (IP/RP−); and > 2 cm IP dissemination and positive lymphadenopathy (IP/RP+). Product-limit and multivariate proportional hazards modeling were used.

Results

Analyses included 417 stage IIIC women who underwent primary cytoreduction with lymphadenectomy to microscopic residual. There were 203, 123, and 91 in the RP, IP/RP−, and IP/RP+ groups, respectively. IP/RP+ and IP/RP− were associated with worse progression-free survival (PFS) (Hazard Ratio (HR) 1.68, 95% confidence interval (CI) 1.23-2.30; HR 1.38, 95% CI 1.04-1.84) vs. RP only. IP/RP+ was associated with worse overall survival (OS) (HR 1.79, 95% CI 1.24-2.57) while IP/RP− trended towards worse OS (HR 1.21, 95% CI 0.85-1.73) vs. RP only. Median PFS for IP/RP+ and IP/RP− groups was 21 and 29 months, respectively, vs. 48 months in the RP group (p = 0.0007) and median OS of 63 and 79 months vs. “not reached,” respectively (p = 0.0038).

Conclusions

Among EOC patients surgically cytoreduced to microscopic residual disease, those upstaged to IIIC by retroperitoneal involvement demonstrated significant improvement in PFS and OS compared to patients with intraperitoneal tumor, suggesting that these women may represent a unique subset of FIGO stage IIIC patients.     

Immunoexpression of B7-H3 in endometrial cancer: relation to tumor T-cell infiltration and prognosis

Objective

B7-H3, a member of the B7 family of immune regulatory ligands regulates T cell-mediated peripheral immune response. The purpose of this study was to correlate the expression of B7-H3 and number of lymphocytes in patients with endometrial cancer.

Material and methods

A total of 107 patients with primary endometrial carcinoma (type I/endometrioid, n = 81; type II, n = 18) and endometrial hyperplasia (n = 8) were investigated. Expression of B7-H3 in endometrial hyperplasia, endometrial carcinoma, and the endothelium of tumor-associated vasculature was assessed using immunohistochemistry from paraffin-embedded tissue blocks. Detection of CD8-positive tumor-infiltrating lymphocytes (TIL) and CD8-positive tumor-associated lymphocytes (TAL) was correlated with the expression of B7-H3.

Results

Patients with high grade tumors and patients with type II carcinomas expressed significantly more B7-H3 than low grade and endometrioid tumors (p = < 0.0001 and p = 0.0001, respectively). The expression of B7-H3 in the endothelium of identified vasculature in the tumor specimens showed similar results with strong relation to high grade tumors (p = 0.001) and type II carcinomas (p = 0.004). We found a significant correlation between B7-H3 expression on cancer cells and tumor T-cell infiltration (TIL) (p = 0.017). In a univariate survival analysis, overexpression of B7-H3 in tumor cells was associated with shortened overall survival (p = 0.005).

Conclusions

B7-H3 is overexpressed on cancer cells and in the endothelium of tumor-associated vasculature in high grade tumors (G3) and type II carcinomas. B7-H3 expression on cancer cells is correlated with the number of T cells infiltrating the tumor. Endometrium tumor development and progression may be associated with downregulation of T-cell-mediated antitumor immunity through B7-H3.     

Impact of beta blockers on epithelial ovarian cancer survival

Objective

Stress may promote ovarian cancer progression through mechanisms including autonomic nervous system mediators such as norepinephrine and epinephrine. Beta blockers, used to treat hypertension, block production of these adrenergic hormones, and have been associated with prolonged survival in several malignancies. We sought to determine the association between beta blocker use and epithelial ovarian cancer (EOC) disease progression and survival.

Methods

We performed an institutional retrospective review of patients with EOC treated between 1996 and 2006. Patients underwent cytoreductive surgery followed by platinum-based chemotherapy. Women were considered beta blocker users if these medications were documented on at least two records more than 6 months apart. Statistical tests included Fisher's exact, Kaplan-Meier, and Cox regression analyses.

Results

248 met inclusion criteria. 68 patients used antihypertensives, and 23 used beta blockers. Median progression-free survival for beta blocker users was 27 months, compared with 17 months for non-users (p = 0.05). Similarly, overall disease-specific survival was longer for beta blocker users (56 months) compared with non-users (48 months, p = 0.02, hazard ratio = 0.56). Multivariate analysis identified beta blocker use as an independent positive prognostic factor, after controlling for age, stage, grade, and cytoreduction status (p = 0.03). Overall survival remained longer for beta blocker users (56 months) when compared with hypertensive patients on other medications (34 months) and patients without hypertension (51 months) (p = 0.007).

Conclusions

In this cohort of patients with EOC, beta blocker use was associated with a 54% reduced chance of death compared with that of non-users.     

Surgical staging of early stage epithelial ovarian cancer: results from the CDC-NPCR ovarian patterns of care study

Objectives

The objectives of this study were to determine the adequacy of surgical staging performed on surgically treated epithelial ovarian cancer (EOC) patients with apparent early stage disease and to determine if receipt of surgical staging had an influence on survival.

Methods

Detailed surgical staging information was collected from medical records for 721 patients diagnosed between 1998 and 2000 with EOC. Patients resided in California or New York and were identified through population-based cancer registries.

Results

Nearly 90% of patients had removal of the omentum and evaluation of bowel serosa and mesentery but only 72% had assessment of retroperitoneal lymph nodes and the majority of patients did not receive biopsies of other peritoneal locations. Only lymph node assessment (as well as node assessment combined with washings and omentectomy) had a statistically significant association with improved survival. The 5-year survival for women with node sampling was 84.2% versus 69.6% for those without this surgical procedure, and patients who did not have lymph node assessment had nearly twice the risk of death as those who did. When patients were stratified by receipt of chemotherapy, lack of node sampling had an effect only on patients who also had no chemotherapy (adjusted HR = 2.2, CI = 1.0-4.5).

Conclusions

The results of this population-based study confirm the prognostic importance of surgical staging for women with EOC, and the important role of gynecologic oncologists in treating these patients. Adjuvant chemotherapy does not appear to further improve survival for those women who receive adequate surgical staging.     

A cost analysis of postoperative management in endometrial cancer patients treated by robotics versus laparoscopic approach

Objective

The purpose of this study is to compare postoperative pain management and costs in endometrial cancer patients who had a robotic-assisted or laparoscopic-assisted hysterectomy.

Methods

This is a retrospective cohort study of all endometrial cancer patients from 9/2005 to 6/2010 who had a completed robotic-assisted or laparoscopic-assisted hysterectomy. All surgeries were performed by gynecologic oncologists on the da Vinci S surgical system. Demographic data, patient-recorded pain scores, pain-management interventions, and postoperative pain medication costs were compared. Data was analyzed using Student's t-tests and Pearson's χ² tests in SPSS.

Results

Two-hundred fifteen (101 robotic and 114 laparoscopic) patients met the inclusion criteria. There were no significant differences between the groups in age, BMI, clinical stage, comorbidities, lymph nodes retrieved, and the number of narcotic vs. non-narcotic drug interventions administered. Robotic patients had a lower number of initial drug interventions (21 vs. 52; P < .001) and total drug interventions (162 vs. 219; P < .001) than laparoscopic patients. Robotics had a lower initial pain score (2.1 vs. 3.0; P = .012). There was a 50% reduction in the pain medication cost on the day of surgery for robotic patients ($12.24 vs. $24.45; P < .01), and a 56% cost reduction for the rest of their length of stay ($3.63 vs. $8.17; P < .01).

Conclusion

Endometrial cancer patients who have robotic surgery experience less initial postoperative pain and have fewer drug interventions. The cost associated for their pain management represents a savings of greater than 50%. These factors demonstrate the value of robotic surgery in regard to postoperative pain management by delivering higher quality care at a lower cost.     

HE4 is an independent prognostic marker in endometrial cancer patients

Objective

To evaluate the prognostic value of pretherapeutic serum HE4 in endometrial cancer in comparison to CA125.

Methods

HE4 and CA125 serum levels were analyzed by means of chemiluminescent microparticle immunoassays in 183 patients with endometrial cancer treated at the Department of Obstetrics and Gynecology, Innsbruck Medical University, between 1999 and 2009. The Kaplan-Meier method and Cox's proportional hazards analysis were performed to determine the prognostic significance of HE4, CA125 and the combination of both markers.

Results

In univariate analysis both markers, HE4 and CA125, were of prognostic value for overall survival (p < 0.001 and p = 0.028) and disease-free survival (p = 0.015 and p = 0.045). In multivariate analysis HE4 was seen to have independent prognostic value in overall survival (HR 2.407, p = 0.017) in contrast to CA125. The combination of both markers showed a higher hazard ratio (HR 4.04, p = 0.023) for overall survival in comparison to HE4 alone. In the subgroup endometrioid histological type (n = 132) only HE4 was of prognostic value for overall survival in univariate (p = 0.001) and multivariate analysis (p = 0.023).

Conclusions

Pretherapeutic serum HE4 levels alone and in combination with CA125 are an independent prognostic marker in endometrial cancer patients.     

Prognosis of ovarian clear cell carcinoma compared to other histological subtypes: a meta-analysis

Objective

To compare the survival outcome between clear cell carcinoma (CCC) and other histological subtypes in epithelial ovarian carcinoma (EOC).

Methods

From January 1974 to February 2011, we identified a total of 31,800 (CCC; 2152, non-CCC; 29648) patients from 12 studies meeting the inclusion criteria.

Results

Heterogeneity tests demonstrated significant between-study variation (I² = 92.1%) with no significant difference in hazard ratio (HR) for death between CCC and non-CCC (HR; 1.16, 95% CI; 0.85-1.57, random-effects model). Comparing the HR based on stage I + II, and stage III + IV, between CCC and non-CCC, showed that CCC patients had a higher hazard rate for death than those with non-CCC of the ovary (stage I + II; HR; 1.17, 95% CI; 1.01-1.36, stage III + IV; HR; 1.65, 95% CI; 1.52-1.79). In a comparison of CCC and serous EOC, advanced stage (III and IV) CCC only showed a poorer hazard rate for death than serous EOC (HR; 1.71, 95% CI; 1.57-1.86).

Conclusion

This analysis suggests that ovarian CCC patients had poorer prognosis than those with other histological subtypes of EOC, especially in advanced EOC stages. Different treatment strategies may be needed for patients with ovarian CCC.     

Burn injuries during pregnancy in Iran

Objective

To report on maternal and fetal outcome in 53 pregnant women seen at a referral burn center.

Methods

Possible links between outcome and maternal age, level of education, marital status, percentage of total body surface area (TBSA) burned, inhalation injury, source and intentionality of the burn, and trimester of pregnancy at the time of the burn were assessed.

Results

Of 5497 women, 53 (1.3%) were pregnant at the time of admission. Maternal and fetal deaths occurred at significantly higher rates in cases of inhalation injury (P = 0.001). The mean percentage of TBSA burned was significantly higher in cases of maternal or fetal death (P < 0.001 for both), and when the burn has a suicidal intent (P = 0.006). The maternal and fetal mortality rates were also higher when the burn was suicidal (P = 0.001 and P = 0.005).

Conclusion

Inhalation injury, suicidal burn injury, and percentage of TBSA burned were correlated with a higher maternal and fetal mortality.     

Timing of fertility preservation procedures in a cohort of female patients with cancer

Objective

Comparison of time intervals from diagnosis to chemotherapy between patients opting for embryo cryopreservation or ovarian tissue cryopreservation.

Study design

Retrospective analysis.

Setting

University hospital in the Netherlands.

Patients and methods

Thirty-five female patients undergoing fertility preservation procedures before treatment with chemotherapy for cancer. Embryo cryopreservation was performed in 12 patients and ovarian tissue cryopreservation in 23 patients. We investigated differences in time intervals (from diagnosis to start of chemotherapy) between patients opting for embryo cryopreservation and patients opting for ovarian tissue cryopreservation. We calculated time intervals between the moment of diagnosis, the moment of referral, the moment of consultation, the moment of finishing of the fertility preservation procedure and the start of chemotherapy.

Results

The median time between diagnosis and referral (median = 18 days) and between referral and consultation (median = 5 days) was comparable in both groups. A significant difference was found between ovarian tissue cryopreservation and embryo cryopreservation for the time interval between consultation and cryopreservation (p = 0.001). Ovarian tissue cryopreservation was completed for half of the patients within 6 days after consultation with the gynecologist, and the hormonal stimulation for embryo cryopreservation was completed for all patients within four weeks (median = 18 days), with a median of 11 days of hormonal stimulation. A significant difference was found between ovarian tissue cryopreservation and embryo cryopreservation in the time interval between fertility preservation and start of chemotherapy (median = 7 vs 19 days, p = 0.019). In sum, the total duration between diagnosis and chemotherapy was significantly shorter for ovarian tissue cryopreservation patients than for embryo cryopreservation patients (median = 47 vs 69 days, p = 0.042).

Conclusion

Embryo cryopreservation can be performed within the standard timeframe of cancer care in patients with breast cancer receiving adjuvant chemotherapy, but if delay of the start of chemotherapy is harmful, ovarian tissue cryopreservation can be done within one week.     

Carcinosarcoma of the ovary: a case-control study

Introduction

Carcinosarcoma of the ovary is a rare tumor with a grim prognosis. Chemotherapy for these tumors is chosen according to guidelines established for epithelial ovarian cancer (EOC). The purpose of this study is to compare response to chemotherapy and survival in patients with advanced stage carcinosarcoma of the ovary.

Methods

We identified women with advanced carcinosarcoma of the ovary who underwent first-line platinum and taxane-based chemotherapy. Each case was matched to two women with serous EOC. Cases and controls were matched by age, stage, and year of diagnosis. The Kaplan-Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the log-rank test and Cox proportional hazards model.

Results

Fifty women treated with first line platinum and taxane-based chemotherapy had advanced carcinosarcoma of the ovary and were selected as cases. The response rates to chemotherapy for cases and controls were 62% and 83% (P = 0.03), respectively. Median progression-free survival was 11 months (95% CI, 8 to 14 months) versus 16 months (95% CI, 12 to 21 months; P = 0.02) and median overall survival was 24 months (95% CI, 18 to 29 months) versus 41 months (95% CI, 33 to 49 months; P = 0.002) for cases and controls, respectively.

Conclusion

Patients with advanced carcinosarcoma of the ovary have a poorer response to platinum and taxane-based first-line chemotherapy and worse survival, compared to patients with serous EOC. Aggressive surgical treatment may play an important role. However, other alternative systemic therapeutic approaches should be sought for patients with carcinosarcoma of the ovary.     

Androgen receptor expression is a biological marker for androgen sensitivity in high grade serous epithelial ovarian cancer

Objectives

In the present study we explore the effects of androgens and anti-androgens on primary cultures of EOC cells. We also investigate the effects of chemotherapy on AR expression. Epithelial ovarian cancer (EOC) arises from ovarian surface epithelial cells (OSE), which express the androgen receptor (AR). Androgen stimulation of OSE cells results in increased proliferation and protection from apoptosis. Nevertheless, in clinical trials anti-androgens have had a low objective response rate in relapsed ovarian cancer.

Methods

1. Androgen receptor (AR) expression and response to androgenic stimulation were correlated in primary ovarian cancer cells derived from ascitic fluid from patients with advanced ovarian cancer,2. AR expression in primary epithelial ovarian cancer was investigated before and after chemotherapy using paired histological samples which had been incorporated into a tissue microarray.

Results

Eleven primary ovarian cancer cultures were established from ascitic fluid. There was wide variation of expression of androgen receptor mRNA between cultures. Cell division increased after dihydro-testosterone (DHT) stimulation in 6 out of 11 primary cultures. The fraction of cells in S-phase increased from 4.4% in cells grown in serum-free medium to 8.3% in cells stimulated with 100 nM of DHT (P < 0.001). The increase in S-phase fraction was abrogated after treatment with the anti-androgen, bicalutamide in 4 out of 5 responsive cultures. There was a strong correlation (r² = 0.7) between nuclear AR expression by immunohistochemistry and S-phase fraction changes in primary cultures.Paired pre- and post-chemotherapy histological samples from 29 patients were incorporated into a tissue microarray (TMA). Nuclear and cytoplasmic AR expression by immunohistochemistry (IHC) decreased significantly after chemotherapy (P < 0.01).

Conclusion

AR expression correlates with increased S-phase fraction in response to androgenic stimulation. Immunohistochemical analysis of AR expression needs to be further tested in clinical trials to select AR positive EOC for anti-androgen therapy. Anti-androgen use early in the course of ovarian cancer is more likely to be effective as these data suggest that androgen receptor expression decreases with exposure to chemotherapy and this may explain the low response rates seen in clinical trials of patients heavily pre-treated with multiple courses of chemotherapy.     

Immunohistochemical expression of Annexin A2 and S100A proteins in patients with bulky stage IB-IIA cervical cancer treated with neoadjuvant chemotherapy

Objective

Abnormal expression of Annexin A2 and S100A proteins has been reported to induce sensitivity/resistance to chemotherapy in a variety of cancers. The aim of this study was to evaluate the significance of Annexin A2 and S100A protein expression to predict response to neoadjuvant chemotherapy and prognostic significance of these protein expressions in bulky stage IB-IIA cervical cancer patients.

Methods

Paired tumor samples (pre- and post-chemotherapy) were obtained from 68 patients who were treated with cisplatin-based neoadjuvant chemotherapy and radical hysterectomy at our hospital from 2006 to 2011. The expression of Annexin A2 and S100A proteins was analyzed by immunohistochemistry.

Results

Thirty-six patients were identified as chemotherapy-response and 32 were non-response. (a). Protein expression in tumor cells: (1). Exposure of tumor cells to chemotherapy results in a change of Annexin A2 and S100A expression (P < 0.05). (2). Annexin A2, S100A8 and S100A9 protein expression correlates with tumor response to chemotherapy (P < 0.05). (b). Protein expression in stromal cells: (1). Expression of Annexin A2, S100A8 and S100A9 was increased, but S100A2 and S100A4 was decreased after exposure to chemotherapy (P < 0.05). (2). Only S100A4 expression was associated with response to chemotherapy (P < 0.05). Multivariate analysis revealed that tumor size (P = 0.022), differentiation (P = 0.000), Annexin A2 expression in stromal cells (P = 0.009), and S100A8 expression in tumor cells (P = 0.008) were independent prognostic factors for progression-free survival of cervical cancer patients.

Conclusions

Expression of some of the measured proteins in tumor and stromal cells correlates with chemotherapy exposure, response to therapy, and progression-free survival.