Correlation of Clinicopathological and Prognostic Characteristics between Endometriosis-Associated and Primary Ovarian Cancer

Abstract Background: To establish the clinicopathological and prognostic correlations between endometriosis-associated and non-endometriosis-associated primary ovarian cancer, with a view to providing a reference guide for revision of diagnostic criteria for malignant transformation of endometriosis.Methods: Retrospectively collected clinicopathological and follow-up data of 174 clear cell and endometrial ovarian cancer patients. Cases were divided into endometriosis-associated and non-endometriosis-associated primary ovarian cancer, and comparative analysis of the clinicopathological characteristics and prognosis conducted.Results: Average age and proportion of menopausal patients in the endometriosis-associated ovarian cancer group were lower relative to the primary ovarian cancer group (P<0.05). Other clinicopathological features examined, including body mass index, age at menopause, operation history, dysmenorrhea, complications, tumor size, tumor side, ascites, CA125, HE4, CA199, stage, differentiation, expression of ER, PR, P53, P16, Ki67, MMR, HNF-1β and Napsin A were not significantly different between the groups (P>0.05). Furthermore, rates of resistance to platinum chemotherapy, relapse, progression-free survival and overall survival were comparable between the two groups (P > 0.05).Conclusion: Endometriosis-associated and primary ovarian cancers of the same pathological type are speculated to be homologous in terms of origin from malignant transformation of endometriosis. It may therefore be necessary to revise the diagnostic criteria for ovarian endometriosis malignancy.

Download Full-text

Second-line Intraperitoneal Platinum-based Therapy Leads to an Increase in Second-line Progression-free Survival for Epithelial Ovarian Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000667 ◽

2016 ◽

Vol 26 (4) ◽

pp. 626-631 ◽

Cited By ~ 2

Author(s):

Michelle M. Boisen ◽

Jamie L. Lesnock ◽

Scott D. Richard ◽

Sushil Beriwal ◽

Joseph L. Kelley ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Gynecologic Oncology ◽

Progression Free Survival ◽

Primary Response ◽

Published Data ◽

Second Line ◽

First Recurrence ◽

Oncology Practice ◽

Platinum Chemotherapy

ObjectiveOnly 3% of patients with epithelial ovarian cancer (EOC) have a longer treatment-free interval (TFI) after second-line intravenous (IV) platinum chemotherapy than with frontline IV therapy. We sought to examine what impact second-line combination IV/intraperitoneal (IV/IP) platinum therapy might have on the ratio of second-line to first-line TFI in patients treated with second-line IP platinum chemotherapy for first recurrence after front-line IV therapy.MethodsA retrospective analysis of women who received combination platinum-based IV/IP chemotherapy for recurrent EOC between January 2005 and March 2011 was conducted. Patients were identified from the tumor registry, and office records from a large gynecologic oncology practice and patient records were reviewed. The first and second TFIs were defined as the time from the end of previous platinum-based therapy to the start of next therapy.ResultsTwenty-five women received IV/IP chemotherapy for their first EOC recurrence after IV chemotherapy. In 10 patients (40%), we observed a longer TFI after IV/IP chemotherapy than after primary IV chemotherapy. For these 10 patients, the median TFI for primary response was 22 months (range, 15–28), whereas median TFI after IV/IP chemotherapy for recurrent disease was 37 months (range, 12–61).ConclusionsFor EOC patients with limited peritoneal recurrence, 40% of patients had a second-line IP-platinum TFI that exceeded their frontline IV-platinum TFI compared to published data. These data support the use of IV/IP chemotherapy as a treatment for recurrence.

Download Full-text

Hypodontia phenotype in patients with epithelial ovarian cancer

Radiology and Oncology ◽

10.2478/raon-2014-0034 ◽

2015 ◽

Vol 49 (1) ◽

pp. 65-70 ◽

Cited By ~ 2

Author(s):

Anita Fekonja ◽

Andrej Cretnik ◽

Danijel Zerdoner ◽

Iztok Takac

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Figo Stage ◽

Clinicopathological Characteristics ◽

Control Group ◽

Malignant Tumours ◽

Cancer Group ◽

Significant Difference ◽

The University ◽

And Control

Abstract Background. Ovarian cancer is usually diagnosed in an advanced stage and the present clinical and diagnostic molecular markers for early OC screening are insufficient. The aim of this study was to identify potential relationship between the hypodontia and epithelial ovarian cancer (EOC). Patients and methods. A retrospective study was conducted on 120 patients with EOC treated at the Department of Gynaecologic and Breast Oncology at the University Clinical Centre and 120 gynaecological healthy women (control group) of the same mean age. Women in both groups were reviewed for the presence of hypodontia and the patients with EOC also for clinicopathological characteristics of EOC according to hypodontia phenotype. Results. Hypodontia was diagnosed in 23 (19.2%) of patients with EOC and 8 (6.7%) controls (p = 0.004; odds ratio [OR] = 3.32; confidence interval [CI], 1.42-7.76). There was no statistically significant difference in patients with EOC with or without hypodontia regarding histological subtype (p = 0.220); they differed in regard to FIGO stage (p = 0.014; OR =3.26; CI, 1.23-8.64) and tumour differentiation grade (p = 0.042; OR = 3.1; CI, 1.01-9.53). Also, bilateral occurrence of EOC was more common than unilateral occurrence in women with hypodontia (p = 0.021; OR = 2.9; CI, 1.15-7.36). We also found statistically significant difference between the ovarian cancer group and control group in presence of other malignant tumours in subjects (p < 0.001). Conclusions. The results of the study suggest a statistical association between EOC and hypodontia phenotype. Hypodontia might serve as a risk factor for EOC detection.

Download Full-text

Clinical relevance of VEGF-receptor status in primary ovarian cancer: A pilot study for future biomarker analyses.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5556 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5556-5556

Author(s):

Pauline Wimberger ◽

Issam Chebouti ◽

Jan Dominik Kuhlmann ◽

Rainer Kimmig ◽

Eberhart Kuhlisch ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Cells ◽

Primary Tumor ◽

Prognostic Significance ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Cancer Tissue ◽

Vegf Receptor ◽

Antiangiogenic Treatment ◽

Primary Ovarian Cancer

5556 Background: Antiangiogenic treatment in addition to platinum/taxane based chemotherapy was shown to improve progression-free survival in first- and second-line chemotherapy in ovarian cancer patients. Predictive markers for antiangiogenic treatment are of high interest. Therefore we investigated VEGF-receptor (VEGFR) expression as possible biomarker candidate in primary ovarian cancer tissue and its clinical impact. Methods: A total of 82 patients with primary ovarian cancer were enrolled into this study. Primary tumor tissue was analyzed for the expression of VEGFR1, VEGFR2 and VEGFR3 by immunhistochemistry. Moreover, the presence of circulating tumor cells (CTC) in the blood was detected by immunomagnetic enrichment and multiplex reverse transcriptase-polymerase chain reaction (Adnatest Ovarian Cancer, Adnagen). Disseminated tumor cells (DTC) in the BM were identified by immunocytochemistry using the pancytokeratin antibodyA45B/B3 and subsequent automatic detection based on staining and cytomorphology. Results: Positivity for at least one VEGFR was observed in 43% of cases. The positivity rates for VEGFR1, -2 and -3 were 34%, 17% and 27%, respectively. VEGFR-status of the primary tumor neither correlated with established clinicopathogical parameters (age, FIGO-stage, nodal status, grading, histological subtype) nor with the presence of CTC or DTC. In addition, VEGFR-status does not provide prognostic significance in regard to progression-free and overall survival (OS). Nevertheless, a trend was observed that patients, being positive for VEGFR3 at primary diagnosis, were more likely to experience suboptimal debulking (p = 0.074). CTC-positivity after adjuvant therapy significantly correlated with OS, but multivariable analysis showed only residual tumor as prognostic factor for OS. Conclusions: The VEGFR-family, albeit frequently expressed in our patient cohort, provided neither prognostic nor predictive relevance, but could probably be a predictor for debulking efficiency. The implementation of VEGFR-status into future biomarker studies should carefully be considered.

Download Full-text

BRCA1 Promoter Methylation and Clinical Outcomes in Ovarian Cancer: An Individual Patient Data Meta-Analysis

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djaa070 ◽

2020 ◽

Vol 112 (12) ◽

pp. 1190-1203 ◽

Cited By ~ 1

Author(s):

Roshni D Kalachand ◽

Britta Stordal ◽

Stephen Madden ◽

Benjamin Chandler ◽

Julie Cunningham ◽

...

Keyword(s):

Ovarian Cancer ◽

Statistical Tests ◽

Meta Analysis ◽

Progression Free Survival ◽

Clinicopathological Characteristics ◽

Mixed Effects ◽

Mixed Effects Modeling ◽

Brca1 Promoter Methylation ◽

Individual Participant ◽

Survival Differences

Abstract Background BRCA1 methylation has been associated with homologous recombination deficiency, a biomarker of platinum sensitivity. Studies evaluating BRCA1-methylated tubal and ovarian cancer (OC) do not consistently support improved survival following platinum chemotherapy. We examine the characteristics of BRCA1-methylated OC in a meta-analysis of individual participant data. Methods Data of 2636 participants across 15 studies were analyzed. BRCA1-methylated tumors were defined according to their original study. Associations between BRCA1 methylation and clinicopathological characteristics were evaluated. The effects of methylation on overall survival (OS) and progression-free survival (PFS) were examined using mixed-effects models. All statistical tests were 2-sided. Results 430 (16.3%) tumors were BRCA1-methylated. BRCA1 methylation was associated with younger age and advanced-stage, high-grade serous OC. There were no survival differences between BRCA1-methylated and non–BRCA1-methylated OC (median PFS = 20.0 vs 18.5 months, hazard ratio [HR] = 1.01, 95% CI = 0.87 to 1.16; P = .98; median OS = 46.6 vs 48.0 months, HR = 1.02, 95% CI = 0.87 to 1.18; P = .96). Where BRCA1/2 mutations were evaluated (n = 1248), BRCA1 methylation displayed no survival advantage over BRCA1/2-intact (BRCA1/2 wild-type non–BRCA1-methylated) OC. Studies used different methods to define BRCA1 methylation. Where BRCA1 methylation was determined using methylation-specific polymerase chain reaction and gel electrophoresis (n = 834), it was associated with improved survival (PFS: HR = 0.80, 95% CI = 0.66 to 0.97; P = .02; OS: HR = 0.80, 95% CI = 0.63 to 1.00; P = .05) on mixed-effects modeling. Conclusion BRCA1-methylated OC displays similar clinicopathological features to BRCA1-mutated OC but is not associated with survival. Heterogeneity within BRCA1 methylation assays influences associations. Refining these assays may better identify cases with silenced BRCA1 function and improved patient outcomes.

Download Full-text

High expression of RRM2 promotes the pathogenesis of malignant ovarian endometriosis.

10.21203/rs.3.rs-342433/v1 ◽

2021 ◽

Author(s):

Binkai Yang ◽

Yuanjing Hu ◽

Tian Wang ◽

Na Li ◽

Wenwen Zhang

Keyword(s):

Gene Expression ◽

Ovarian Cancer ◽

Malignant Transformation ◽

Expression Profiles ◽

Quantitative Polymerase Chain Reaction ◽

Gene Expression Profiles ◽

High Expression ◽

Ovarian Endometriosis ◽

Ki 67 ◽

Significant Difference

Abstract Objective: Our objective was to investigate the upregulated expression of ribonucleotide reductase M2 (RRM2) in the ectopic endometrium (EC) of ovarian endometriosis (OE) patients that may indicate malignant transformation. RRM2 may be used as a marker of OE, which contribute to the research of the mechanism of the malignant transformation of OE.Methods: The gene expression profiles of ovarian cancer and OE were downloaded from Gene Expression Omnibus (GEO), and a common hub gene, RRM2, was identified. The expression of RRM2 was low in OE and high in ovarian cancer. A total of 44 patients with endometriosis-associated ovarian cancers (EAOC) and 44 with OE were enrolled in this study. Immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of RRM2, while the relationship between RRM2 and Ki-67 was analyzed by IHC co-localization. Results: There was no significant difference in the expression of RRM2 in the eutopic endometrium (EU), EC, and cancer tissues of EAOC patients. Compared with OE patients, the mRNA and protein expression levels of RRM2 were higher in the EC of EAOC patients (p＜0.01). Moreover, the high expression of RRM2 was consistent with the expression of Ki-67 in EC of EAOC patients.Conclusions: The upregulated expression of RRM2 in the EC of OE patients may indicate malignant transformation. RRM2 may be used as a marker of OE, which allows the investigation of the mechanism of the malignant transformation of OE.

Download Full-text

Ex vivo assay prediction of progression free interval following platinum chemotherapy in primary ovarian cancer

Journal of Clinical Oncology ◽

10.1200/jco.2005.23.16_suppl.5098 ◽

2005 ◽

Vol 23 (16_suppl) ◽

pp. 5098-5098

Author(s):

A. Nickles Fader ◽

J. Comerci ◽

J. Kelley ◽

H. Schellhas ◽

S. Hosford

Keyword(s):

Ovarian Cancer ◽

Ex Vivo ◽

Primary Ovarian Cancer ◽

Free Interval ◽

Platinum Chemotherapy ◽

Ex Vivo Assay

Download Full-text

A Modified Intraperitoneal Chemotherapy Regimen for Ovarian Cancer: Technique and Treatment Outcomes

Cancers ◽

10.3390/cancers13194886 ◽

2021 ◽

Vol 13 (19) ◽

pp. 4886

Author(s):

Ji Hyun Kim ◽

Hyeong In Ha ◽

Min Hae Kim ◽

Mi Ra Han ◽

Sang-Yoon Park ◽

...

Keyword(s):

Ovarian Cancer ◽

Treatment Outcomes ◽

Chemotherapy Regimen ◽

Gynecologic Oncology ◽

Progression Free Survival ◽

Completion Rate ◽

Study Cohort ◽

Colonic Surgery ◽

Gynecologic Oncology Group ◽

Primary Ovarian Cancer

This study aimed to investigate treatment outcomes concerning three institutional modifications to intraperitoneal (IP) chemotherapy for patients with ovarian cancer. The medical records of 27 patients treated with IP chemotherapy were retrospectively reviewed. All patients had three IP chemotherapy institutional modifications; modified Gynecologic Oncology Group 172 regimen was used for the chemotherapy regimen. With institutional modifications, 63.0% (17/27) completed all six cycles of IP chemotherapy. Of the 17 and 10 patients with primary and recurrent ovarian cancer, respectively, 55.6% (15/27) underwent left colonic surgery, including low anterior resection. In patients with primary ovarian cancer, the IP chemotherapy completion rate was 76.5% (13/17). In patients with and without left colonic surgery, the IP chemotherapy completion rates were 53.3% (8/15) and 75.0% (9/12), respectively. No complications related to left colonic surgery during IP chemotherapy were identified. The most frequent grade 3–4 toxicities were gastrointestinal toxicities (33.3%) and neutropenia (29.6%). The median progression-free survival was 19.5 months in all patients and 25.2 months in patients with primary ovarian cancer. Three institutional modifications to IP chemotherapy increased the completion rate for planned IP chemotherapy, even after left colonic surgery. Further studies involving a larger study cohort are required to confirm survival outcomes using these modifications.

Download Full-text

The Diagnostic Superiority of the HE-4 Marker over CA-125 and CA 19-9 in the Differentiation of a Large Pelvic Tumor – a Case Report

Journal of Endometriosis and Pelvic Pain Disorders ◽

10.5301/je.5000150 ◽

2013 ◽

Vol 5 (1) ◽

pp. 40-45

Author(s):

Anita Chudecka-Głaz ◽

Janusz Menkiszak ◽

Aneta Cymbaluk-Płoska ◽

Donald Rutkowski ◽

Miłosz Kawa ◽

...

Keyword(s):

Ovarian Cancer ◽

Ca 125 ◽

Greater Omentum ◽

Specific Marker ◽

Pelvic Tumor ◽

Ovarian Endometriosis ◽

Primary Ovarian Cancer ◽

Normal Limits ◽

Pelvic Tumors ◽

Ovarian Diseases

The HE-4 protein is a promising specific marker for the diagnosis of malignant pelvic tumors. The paper presents the case of a 41-year-old patient with a multi-chamber ovarian tumor several centimeters in diameter suspected to be a primary ovarian cancer or a metastatic one of gastrointestinal origin. The value of the HE-4 marker which is highly specific for an ovarian cancer was within normal limits and amounted to 24.33 pmol/L. The patient underwent surgery involving the unilateral removal of adnexa and the greater omentum during which the sample from the second ovary was collected. Histologic examination revealed ovarian endometriosis; however, diagnosis of the gastrointestinal tract did not reveal any abnormalities. The case presented also confirms the excellent sensitivity of the HE-4 marker in very difficult clinical cases, as well as its utility in the differential diagnosis of advanced endometriosis and malignant ovarian diseases.

Download Full-text

Persistence of EpCAM-positive disseminated tumor cells after platinum-based chemotherapy in the bone marrow of patients with primary ovarian cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.16023 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 16023-16023

Author(s):

P. Wimberger ◽

M. Heubner ◽

R. Kimmig ◽

M. E. Scheulen ◽

S. Kasimir-Bauer

Keyword(s):

Ovarian Cancer ◽

Bone Marrow ◽

Tumor Cells ◽

Gradient Centrifugation ◽

Progression Free Survival ◽

Disseminated Tumor Cells ◽

Rank Test ◽

Primary Ovarian Cancer ◽

Platinum Based Chemotherapy ◽

The Impact

16023 Background: The impact of chemotherapy on disseminated tumor cells (DTC) in ovarian cancer is still unknown. Therefore we evaluated in 30 patients with primary ovarian cancer, undergoing radical tumor debulking surgery, (1) the influence of first-line chemotherapy with carboplatinum and paclitaxel on DTC elimination in bone marrow (BM) and peripheral blood (PB), (2) the coexpression of the epitelial antigen EpCAM on DTC and (3) the impact on progression free survival (PFS). Methods: DTC were detected in PB (20ml) and bilateral BM aspirates (10ml) using density gradient centrifugation and immunocytochemistry, applying the anti-cytokeratin antibody A45-B/B3. EpCAM-positive DTC were analyzed by using the antibodies HEA-125-FITC and Ber-EP4-FITC. PFS was estimated using the Kaplan-Meier method and statistically evaluated using a two-sided log-rank test. A significant increase or decrease of DTC was assessed if the difference was = 2 DTC. Results: Before chemotherapy, we identified DTC in 16% of PB samples with a mean number of 2 cells (range 1–3) and in 50% of BM samples with a mean number of 3 cells/9x10E6 BM cells (range 1–8). After chemotherapy, DTC were detected in PB in only one patient but still in 50% of BM samples with a with a mean number of 17 cells/9x10E6 BM cells (range 1–100). In BM, chemotherapy completely eliminated DTC in 30% of the patients, no significant change was documented in 47% and a significant enhancement of DTC was shown in 33%, including 8 patients (27%) who had no DTC before chemotherapy. In case of significant increase of DTC, patients showed a trend for reduced PFS (12.8 months ± 0.7; mean PFS ± SEM) in comparison to patients with no increase (19.3 months ± 1.4) or decrease of DTC (p=0.07). DTC, persisting after chemotherapy, co-expressed EpCAM. Conclusions: It has to be considered, whether these patients with persisting EpCAM-positive DTC in BM might profit from an additive immunotherapy e.g. by the intraperitoneal application of a trifunctional antibody targeting EpCAM, CD3 and accessory cells. No significant financial relationships to disclose.

Download Full-text