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.     

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.     

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.     

Pre-treatment tumor expression of ERCC1 in women with advanced stage epithelial ovarian cancer is not predictive of clinical outcomes: a Gynecologic Oncology Group study

Objective

Excision repair cross-complementation group 1 (ERCC1) is required for the repair of platinum-induced DNA damage. This study sought to assess the prognostic value of ERCC1 expression, measured by immunohistochemistry (IHC) using a highly specific antibody, in advanced epithelial ovarian cancer (EOC) patients treated with platinum-based chemotherapy.

Methods

Formalin-fixed, paraffin-embedded tumors were collected from two GOG phase III trials (GOG-172 and GOG-182) of patients with stage III/IV EOC treated with platinum-based chemotherapy. ERCC1 was detected by (IHC) using FL297 polyclonal antibody and tumors were categorized as negative or positive, based on nuclear staining of tumor cells. ERCC1 genotyping was performed as previously reported. Associations between ERCC1 expression and clinical characteristics, platinum responsiveness, progression-free survival (PFS) or overall survival (OS) were evaluated.

Results

Of 408 eligible patients, 27% had tumors that were ERCC1 positive. ERCC1 expression was not associated with clinical characteristics or platinum-responsiveness. Women with ERCC1-positive versus -negative tumors had similar median PFS (17.9 months versus 17.5 months, respectively, p = 0.59), median OS (52.0 months versus 47.0 months, respectively, p = 0.30), risk of disease progression (adjusted hazard ratio [HR] = 0.90, 95% confidence interval (CI): 0.71-1.15, p = 0.41), and risk of death (adjusted HR = 0.81, 95% CI: 0.61-1.07, p = 0.14). ERCC1 expression, as measured by IHC, was not associated with single nucleotide polymorphisms (SNPs), in codon 118 and C8092A, of the ERCC1 gene.

Conclusions

ERCC1 expression, measured by IHC in pre-treatment tumor specimens, using a highly specific antibody, has limited clinical value in patients with advanced EOC treated with platinum and taxane based chemotherapy.     

Single nucleotide polypmorphisms in ERCC1 are associated with disease progression, and survival in patients with advanced stage ovarian and primary peritoneal carcinoma; a Gynecologic Oncology Group study

Objective

This study evaluated common polymorphisms in excision repair cross-complementation group 1 (ERCC1) involved in repair of platinum-induced DNA damage in advanced-stage, epithelial ovarian/peritoneal/tubal cancer (EOC/PPC/FTC) patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy.

Methods

Pyrosequencing was performed to examine single nucleotide polymorphisms (SNPs) in codon 118 and C8092A in ERCC1 in leukocyte DNA from the Gynecologic Oncology Group phase III protocol, GOG-182. Kaplan-Meier method and adjusted Cox regression modeling were used to examine associations between ERCC1 polymorphisms and progression-free survival (PFS) and overall survival (OS).

Results

The genotype distribution at codon 118 (n = 278) in ERCC1 for CC, CT, and TT was 23%, 45% and 32%, and the median OS was 32, 47 and 43 months, respectively. Patients with the CT + TT versus CC genotype in codon 118 in ERCC1 were at a reduced risk of death (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.49-0.95, p = 0.025). The genotype distribution for C8092A in ERCC1 (N = 280) was 50%, 42% and 8%, and the median OS was 45, 40 or 30 months for CC, CA and AA, respectively. Women with the CA + AA versus CC genotype in C8092A in ERCC1 had a trend suggesting an increased risk of death (HR = 1.29, 95% CI = 0.97-1.72, p = 0.077).

Conclusions

The polymorphism in codon 118 in the DNA repair gene ERCC1 was an independent predictor for better survival in EOC/PPC/FTC patients treated with intravenous carboplatin- and paclitaxel-based chemotherapy. The relationship between the C8092A polymorphisms in ERCC1 and survival was modest with an effect size that was not always statistically significant.     

Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes among women with advanced stage ovarian cancer treated with platinum and taxane-based chemotherapy: a Gynecologic Oncology Group study

Purpose

Efflux transporters of the ATP-binding cassette (ABC) family are major determinants of chemoresistance in tumor cells. This study examined associations between functional variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes in patients with epithelial ovarian/primary peritoneal cancer (EOC/PPC) following platinum and taxane-based chemotherapy.

Methods

Sequenom iPLEXTMGOLD Assay and MALDI-TOF platform were used to genotype the non-synonymous G2677T/A (rs2032582; encoding Ala893Ser/Thr) and synonymous C3435T (rs1045642; encoding Ile1145Ile) variants in ABCB1, the non-synonymous G1249A variant in ABCC2 (rs2273697; encoding Val417Ile), and the non-synonymous C421A variant in ABCG2 (rs2231142; encoding Q141K, Gln141Lys) in normal DNA from up to 511 women in Gynecologic Oncology Group (GOG) phase III trials, GOG-172 or GOG-182. Progression-free survival (PFS) and overall survival (OS) were analyzed in relation to genetic polymorphisms using Kaplan-Meier and Cox proportional hazards model.

Results

The C421A variant (CA + AA versus CC) in ABCG2 was associated with a 6-month longer median PFS (22.7 versus 16.8 months, p = 0.041). In multivariate analysis, patients with variant genotypes were at a reduced risk of disease progression (hazard ratio [HR] = 0.75, 95% confidence interval [CI] = 0.59-0.96, p = 0.022). The association between C421A and OS was not statistically significant (HR = 0.88, 95% CI = 0.67-1.15, p = 0.356). None of the other variants measured in either ABCB1 or ABCC2 was associated with PFS or OS.

Conclusion

The C421A variant in ABCG2, previously shown to be associated with enhanced protein degradation and drug sensitivity, was associated with longer PFS in advanced stage EOC/PPC patents treated with platinum + taxane-based chemotherapy. This finding requires further validation.     

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.     

A common variation in the cannabinoid 1 receptor (CNR1) gene is associated with pre-eclampsia in the Central European population

Objective

Recently it has been proposed that tightly regulated levels of endogenous cannabinoids play a fundamental role in early placental development. The aim of this study was to investigate associations of three single-nucleotide polymorphisms (SNPs) in the cannabinoid 1 receptor (CNR1) gene (rs1049353, rs12720071 and rs806368) and their inferred haplotypes with pre-eclampsia, a severe pregnancy-associated condition characterized by abnormal development and remodeling of spiral decidual arteries.

Study design

The case-control study comprised a total of 115 pre-eclamptic women and 145 healthy pregnant controls, all originating from the Central-European Czech population. Using PCR-based methods, we tested rs1049353, rs12720071 and rs806368 in the CNR1 gene and haplotypes were constructed.

Results

Statistically significant difference in genotype distributions of rs806368 (p_g < 10⁻³) was observed when comparing the cases and the controls; the cases presenting with significantly lower proportion of CC homozygotes. In multivariate modeling, the rs806368 served as a predictor for pre-eclampsia development (β = 0.15; p = 0.04). Haplotype analysis revealed presence of four common haplotypes; the CAA haplotype being less frequent in pre-eclamptic cases compared to the controls (p < 0.008). Analysis of regression models confirmed the independent prediction role of AAC haplotype for pre-eclampsia onset (β = −0.18; p = 0.03).

Conclusion

This is the first study focusing on the relationship between SNPs in the CNR1 gene and pre-eclampsia risk. Although limited by a relatively small sample size, the study indicates that rs806368 in the CNR1 gene may act as a susceptibility marker for pre-eclampsia in humans.     

Survival impact of capsule rupture in stage I clear cell carcinoma of the ovary in comparison with other histological types

Objective

We analyzed a large number of stage I clear cell carcinoma of the ovary (CCC) patients to estimate the survival impact of the capsule status in stage I CCC patients, particularly in comparison with non-CCC patients.

Methods

Clinicopathologic data on 564 patients with stage I epithelial ovarian cancer (EOC) collected under the central pathological review system were subjected to uni- and multivariable analyses to evaluate the disease-free survival (DFS) and overall survival (OS).

Results

There was no significant difference in both the OS and DFS of CCC patients between IA and IC(ir) (intraoperative capsule rupture) {IA vs. IC(ir); OS: P = 0.1402, DFS: P = 0.2701}. In contrast, CCC patients at IC(non-ir) {IC excluding for IC(ir), such as preoperative capsule rupture, positive ascites/washing, and surface involvement} showed a poorer OS and DFS than those at IC(ir), or those at the corresponding stage in non-CCC. In multivariable analysis, the capsule status was an independent prognostic factor of a poor OS and DFS {OS: HR, 2.832; 95% CI 1.156-6.938; P = 0.023; DFS: HR, 4.327; 95% CI, 1.937-9.667; P = 0.0004)} {In contrast, non-CCC: N.S. (OS/DFS)}. Furthermore, in CCC patients, intraperitoneal recurrences were more frequently observed in IC(non-ir) CCC than IA or IC(ir) CCC (P = 0.0083) {In contrast, non-CCC: N.S.}.

Conclusion

This study suggests that CCC patients other than those with intraoperative capsule rupture show a considerable risk for mortality despite adjuvant chemotherapy.     

Prognostic value of metabolic tumor volume measured by FDG-PET/CT in patients with cervical cancer

Objective

To determine if preoperative metabolic tumor volume (MTV) measured by integrated ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (FDG-PET/CT) imaging has prognostic value in patients with cervical cancer treated primarily with radical hysterectomy.

Methods

Patients with FIGO stage IB to IIA cervical cancer were imaged with FDG-PET/CT before radical surgery. MTV was measured from attenuation-corrected FDG-PET/CT images using a standard uptake value (SUV)-based automated contouring program. We evaluated the relationship of MTV to disease-free survival (DFS).

Results

A total of 63 patients were included in the study. The cut-off value for predicting recurrence was determined using a receiver operating characteristic (ROC) curve. MTV in this study was found to be correlated with lymph node (LN) metastasis, parametrium (PM) involvement, FIGO stage, and SUV_max. In univariate analysis, MTV ≥ 23.4 mL (HR 1.017, 95% confidence interval (CI) 1.005-1.029, P = 0.004), SUV_max ≥ 9.5 (HR 5.198, 95% CI 1.076-25.118, P = 0.04), LN metastasis (HR 12.338, 95% CI 1.541-98.813, P = 0.018), PM involvement (HR 14.274, 95% CI 1.785-114.149, P = 0.012), and lymphovascular space invasion (HR 8.871, 95% CI 1.104-71.261, P = 0.04), were related to DFS. In multivariate analyses, age (HR 0.748, 95% CI 0.587-0.952, P = 0.018) and MTV ≥ 23.4 mL (HR 49.559, 95% CI 1.257-1953.399, P = 0.037) were determined to be independent prognostic factors of DFS.

Conclusion

Preoperative MTV is an independent prognostic factor for DFS in patients with cervical cancer treated by radical surgery.     

Insurance status and racial differences in uterine cancer survival: a study of patients in the National Cancer Database

Objective.

To examine the impact of race and insurance on survival among a large cohort of uterine cancer patients from the National Cancer Database (NCDB).

Methods.

Women diagnosed with stages I-III uterine cancer between 2000 and 2001 were selected from the NCDB. Kaplan-Meier (KM) and multivariate Cox proportional hazards were used to estimate 4 year survival rates and hazard ratios (HR) and 95% confidence intervals (CIs), respectively.

Results.

Among the 39,510 evaluable patients, African Americans had a higher risk of death compared to whites (HR = 1.43 95% CI 1.31-1.56) after adjusting for age, clinical and facility factors and zip code level education. After additional adjustment for treatment, the risk death decreased among African Americans (HR = 1.33 95%CI 1.21-1.46) and subsequent adjustment for insurance further reduced the hazard of death (HR = 1.28 95% CI 1.17-1.40). Patients with insurance other than private had an increased risk of death (uninsured HR = 1.44 95% CI 1.20-1.72, Medicaid HR = 1.70, 95% CI 1.46-1.99, Medicare among patients aged 18-64 HR = 2.49, 95% CI 2.10-2.95, Medicare among patients aged 65-99 HR = 1.22, 95% 1.11-1.34).

Conclusions.

The largest contributors to African American/white survival disparities in this study were clinical factors, including stage at diagnosis, grade and histopathology. Patients without private health insurance had worse uterine cancer survival that may be improved through future health care reform aimed at improving access to preventive services and adequate treatment.     

Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility

Objective

Endometriosis has been considered an epigenetic disease. Single nucleotide polymorphisms (SNPs) located in genes encoding enzymes of the folate and choline metabolism may affect DNA methyltransferase activity.

Study design

We studied 16 SNPs in 12 folate and choline metabolism genes, including BHMT (rs7356530 and rs3733890), BHMT2 (rs625879), CBS (844ins68), CHDH (rs893363 and rs2289205), CHKA (rs7928739), MTHFD1 (rs2236225), MTHFR (rs1801133), MTR (rs1805087), MTRR (rs1801394), PCYT1A (rs712012 and rs7639752), PEMT (rs4244593 and rs4646406) and TCN (rs1801198) in one hundred and sixty-three infertile women with minimal endometriosis and one hundred and fifty fertile women.

Results

There were no significant differences between genotype and allele frequencies of these gene variants in infertile women with endometriosis (n = 163) and controls (n = 150). The lowest, but not statistically significant, p values of the trend test were observed for the CBS 844ins68 and MTR rs1805087 (p_trend = 0.0527 and p_trend = 0.0771, respectively) polymorphisms. However, the exhaustive multifactor dimensionality reduction analysis revealed an epistatic interaction between rs1801133 of MTHFR and rs4244593 of PEMT in endometriosis-associated infertility (p = 0.0240).

Conclusions

Our results showed moderate evidence for the contribution of SNPs located in genes encoding folate and choline metabolism enzymes to infertility in women with endometriosis.     

Preoperative determinants for failure of transobturator tapes in the management of female urodynamic stress incontinence

Objectives

To determine significant preoperative risk factors for failure of transobturator tapes.

Methods

Secondary analysis of data from the E-TOT (Evaluation of Transobturator Tapes) study. Patient-reported outcomes (n = 310) and objective outcomes (n = 297) were analyzed using univariate and multivariate analyses.

Results

On univariate analysis, body mass index (BMI) ≥  35, maximum urethral closure pressure (MUCP) ≤ 30 cm H₂O, preoperative mixed incontinence on urodynamics, history of at least one previous incontinence procedure, and preoperative symptoms of urgency, nocturia, or urgency incontinence were associated with failure. On multivariate regression, BMI ≥ 35 (OR 6.37; 95% CI, 1.73-23.44; P = 0.005), nocturia (OR 2.18; 95% CI, 1.04-4.58; P = 0.039), urgency incontinence (OR 3.35; 95% CI, 1.07-10.51; P = 0.039), and previous incontinence surgery (OR 2.33; 95%CI, 1.1-5.48; P = 0.048) were independently associated with patient-reported failure. MUCP ≤ 30 cm H₂O (OR 7.06; 95% CI, 2.85-17.48; P < 0.001) and previous incontinence procedure (OR 6.22; 95%CI, 2.34-16.52; P < 0.001) were independently associated with objective failure.

Conclusion

History of previous incontinence surgery was the only independent risk factor for failure of transobturator tapes based on both the patient-reported and objective outcome.     

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.     

Genetic variation in CD83 and risks of cervical and vulvar cancers: a population-based case-control study

Objectives

The CD83 glycoprotein is a marker of dendritic cell maturation that may contribute to the T cell response to oncogenic human papillomavirus (HPV) infection. Whether single nucleotide polymorphisms (SNPs) in CD83 influence the risk of HPV-related genital cancers has not been adequately studied. We investigated whether the common genetic variation of the CD83 region was associated with the risks of cervical and vulvar cancers in a population-based case-control study conducted in the Seattle-Puget Sound Region.

Methods

A total of 17 tagSNPs were genotyped in the CD83 region of 886 cervical cases, 517 vulvar cases and 1100 controls. Odds ratio (OR) and 95% confidence intervals (CI) were computed to assess the risk of cervical and vulvar cancers. The interaction between the tagSNPs and cigarette smoking was also explored.

Results

TagSNPs in the CD83 chromosomal region were not associated with risk of either cervical or vulvar cancer. TagSNP rs853360 was associated with a decreased risk of cervical squamous cell carcinoma (SCC) (OR = 0.80; 95% CI: 0.66-0.98).

Conclusions

Our results do not suggest that the common genetic variation of CD83 is related to cervical or vulvar cancers. The association between tagSNP rs853360 and risk of cervical SCC is likely to be due to chance. If larger or pooled studies confirm our results, CD83 has little or no influence in the risk of HPV-related cancers.     

Prevalence of cysts in epithelial ovarian cancer

Objective

Ovarian carcinomas mostly appear as large cystic masses. However, the exact prevalence of cysts in epithelial ovarian cancer (EOC) has never been documented as well as the tumor factors that are related to the presence of cysts. Demonstrating the prevalence of cysts in EOC is essential for research focused on predictive and prognostic biomarkers in ovarian cyst fluid.

Study design

From 233 patients with primary EOC who underwent surgery, pathological data were collected from pathology reports. Univariate and multivariate logistic regression were used to analyze the relationship between the presence of cysts and other tumor characteristics.

Results

Cysts in EOC were present in 83.7% of the patients and were mostly (61%) multilocular. The most common histological subtypes (serous, mucinous, endometrioid, clear cell) contained cysts in more than 85% of the cases. In univariate regression analysis, early FIGO stage, low tumor grade and a large tumor size were significantly associated with the presence of cysts (OR (95% CI) = 5.312 (1.81-15.57), 6.906 (2.31-20.66) and 1.169 (1.08-1.27), respectively). In multivariate regression analysis, apart from tumor size, only tumor grade was independently associated with the presence of cysts (adjusted OR (95% CI) = 4.234 (1.36-13.22)).

Conclusions

The large majority of all EOCs contained cysts. Histological subtype, FIGO stage, tumor necrosis and age were not associated with the presence of cystic EOC. In contrast, tumor grade and tumor size were independently related to the presence of cystic EOC. This means that cystic EOCs represent a subgroup of larger and more well-differentiated tumors. The evident relationship between the presence of cysts and differentiation grade is interesting from a clinical point of view as grading is especially important for the prognosis and treatment of patients with stage I EOC.     

Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers

Objective

There are few validated relapse prediction biomarkers for epithelial ovarian cancer (EOC). We have shown progranulin (PGRN) and secretory leukocyte protease inhibitor (SLPI) are up regulated, overexpressed survival factors in EOC. We hypothesized they would predict presence of occult EOC.

Method

PGRN, SLPI, and the known biomarker HE4 were measured in EOC patient plasma samples, prospectively collected every 3 months from initial remission until relapse. Clinical data and CA125 results were incorporated into statistical analyses. Exploratory Kaplan-Meier estimates, dividing markers at median values, evaluated association with progression-free survival (PFS) and overall survival (OS). Area-under-the-curve (AUC) statistics were computed from receiver operating characteristic (ROC) curves to evaluate discrimination ability. A Cox proportional hazards model assessed the association between PFS, OS, and biomarkers, adjusting for clinical prognostic factors.

Results

Samples from 23 advanced stage EOC patients were evaluated. PGRN at 3 months was the only biomarker independently associated with PFS (P < 0.0001) and OS (P < 0.003). When used to predict progression by 18 months, sensitivity and specificity were 93% and 100%, respectively, with AUC = 0.944. The Cox model hazard ratio for PFS, divided at 59 ng/ml by ROC analysis and adjusted for clinical factors, was 23.5 (95% CI: 2.49-220). Combinations with SLPI, HE4, and/or CA125 did not improve the model.

Conclusions

We report pilot data indicating a potential independent association of PGRN on EOC patient PFS and OS. A validation study will be required to confirm this finding and to inform whether PGRN warrants evaluation as a potential screening biomarker.     

The impact of tumor morcellation during surgery on the prognosis of patients with apparently early uterine leiomyosarcoma

Objective.

Uterine leiomyosarcoma (LMS) is usually diagnosed after surgery for leiomyoma; thus tumor morcellation frequently occurs. We evaluated the impact of tumor morcellation during surgery on the prognosis of patients with apparently early uterine LMS.

Methods.

Outcomes were retrospectively compared between patients who underwent total abdominal hysterectomy without tumor morcellation and those who underwent surgery that included abdominal, vaginal or laparoscopic tumor morcellation.

Results.

We assessed 56 consecutive patients with stage I and II uterine LMS between 1989 and 2010, 25 with and 31 without tumor morcellation. There were no significant between group differences in age, parity, menopausal status, body mass index, stage, mitotic count, tumor grade, lymph node dissection, adjuvant therapy, and follow-up duration. However, tumor size was significantly smaller (9.8 cm vs. 7.3 cm, P = 0.022) and ovarian tissue was more frequently preserved (38.7% vs. 72%, P = 0.013) in patients with tumor morcellation. In univariate analysis, only tumor morcellation was significantly associated with poorer disease-free survival (DFS) (odds ratio [OR], 2.59; 95% confidence interval [CI], 1.03-6.50; P = 0.043), and higher stage (I vs. II; (OR, 19.12; 95% CI, 1.19-307.11; P = 0.037)) and tumor morcellation (OR, 3.07; 95% CI, 1.05-8.93; P = 0.040) were significantly associated with poorer overall survival (OS). In multivariate analysis, higher stage (OR, 20.34; 95% CI, 1.27-325.58; P = 0.033) and tumor morcellation (OR, 3.11; 95% CI, 1.07-9.06; P = 0.038) were significantly associated with poorer OS. The percentage of patients with abdomino-pelvic dissemination, as shown by peritoneal sarcomatosis or vaginal apex recurrence, was significantly greater in patients with than without tumor morcellation (44% vs. 12.9%, P = 0.032).

Conclusion.

Tumor morcellation during surgery increased the rate of abdomino-pelvic dissemination and adversely affected DFS and OS in patients with apparently early uterine LMS.     

Variants in DENND1A and LHCGR are associated with endometrioid adenocarcinoma

Objective

The aim of this study was to explore the polycystic ovary syndrome (PCOS) related single nucleotide polymorphisms (SNPs) rs13405728 (in gene LHCGR), rs13429458 (in gene THADA) and rs2479106 (in gene DENND1A) in women with endometrial carcinoma.

Methods

We conducted a case-control study comprising 96 Han Chinese women with endometrial carcinoma, and 192 healthy controls. SNPs rs13405728, rs13429458 and rs2479106 were genotyped by polymerase chain reaction (PCR) and direct sequencing. The effects of body mass index (BMI) and age were evaluated using an unconditional logistic regression model adjusted for potential confounders.

Results

The allele frequencies of SNPs rs2479106 and rs13405728 were significantly different (P < 0.05) between endometrial carcinoma group and control group, and the difference was especially significant in the subgroup of endometrioid adenocarcinoma. Genotyping analysis showed that allele G in rs2479106 and allele A in rs13405728 could confer risk to endometrioid adenocarcinoma.

Conclusions

Our results suggest that SNPs rs2479106 in gene DENND1A and rs13405728 in gene LHCGR are associated with endometrioid adenocarcinoma.