IL-17A and CCL2 in blood serum and circulating neutrophils in patients with ovarian tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17536-e17536
Author(s):  
Snezhanna Gening ◽  
Tatyana Abakumova ◽  
Tatyana Gening
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Statistical Processing ◽  
Stage Iv ◽  
Ovarian Tumors ◽  
Stage I ◽  
Stage Iii ◽  
Ccl2 Expression ◽  
Ccl2 Level ◽  
Benign Ovarian Tumors

e17536 Background: During the ovarian carcinogenesis, circulating neutrophils (Nph) phenotype switches to the pro-tumor, with an increase in the Nph C-C motif ligand 2 (CCL2) expression. Proinflammatory interleukin-17A (IL-17A) is able to induce the CCL2 expression in Nph. The study aimed to evaluate the IL-17A and CCL2 levels in serum and circulating Nph in patients with ovarian tumors. Methods: The study included 97 ovarian cancer (OC) patients, 30 patients with benign ovarian tumors (BT) and the control (n=22). The levels of IL-17A (LLC "Cytokine", Russia) and CCL2 (Vector-Best-Volga, Russia) in serum and Nph lysate were assessed by ELISA. The systemic inflammation was assessed by neutrophil to lymphocyte ratio (NLR). Informed voluntary consent was obtained from all women. Statistical processing was performed using one-way ANOVA, Spearman correlations (Statistica 13.0 (TIBCO, USA)). Results: We found an increase in NLR in BT (4.3 ± 1.0) compared with the control (2.2 ± 0.1) (p = 0.020), a decrease in stage I-II OC (2.4 ± 0.2) compared with BT (p = 0.053), and an increase in stage III (4.5 ± 0.9) and IV (4.6 ± 0.5) compared with stage I-II OC (p = 0.054 and p = 0.046, respectively). The cytokines levels are presented in Table. The serum level of IL-17A in BT was higher than in the control (p = 0.010). In stage I-II OC, the serum IL-17A level was decreased in comparison with the BT (p = 0.004). In stage IV OC, the serum IL-17A was higher than in stage I-II (p = 0.015) and the control (p = 0.017). The level of IL-17A in Nph in BT did not differ from the control. In all stages of the OC, the IL-17A Nph level was lower than in the control (p1, 2, 3 = 0.0001). In stage IV OC, the expression of IL-17A in Nph was lower compared with stage III (p = 0.031). The serum and Nph levels of IL-17A were correlated only in stage I-II OC (r = 0.679, p = 0.011). The CCL2 serum levels in BT (p = 0.0002) and OC stage I-II, III, IV were higher compared with the control (p1 = 0.031, p2 = 0.001, p3 = 0.0005, respectively). The Nph CCL2 level was higher in BT than in the control (p = 0.001). In stage I-II OC, the expression of CCL2 in Nph was higher than in the control (p = 0.034), but lower than in the BT (p = 0.003). In OC stages III and IV, the Nph CCL2 level was higher than in the control, but did not differ from that in BT and stages I-II. In stage III OC, the CCL2 level in Nph negatively correlated with the serum IL-17A level (r = -0.405, p = 0.049). Conclusions: The pro-tumor polarization of circulating Nph is not IL-17A-dependent in patients with ovarian tumors. The patterns of the systemic immune response differ in benign ovarian tumors, early, and advanced ovarian cancer.[Table: see text]

Residual tumor status in clinical trials of advanced ovarian cancer: A systematic review

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15024-15024
Author(s):  
M. Beltrán ◽  
X. Hernández ◽  
C. Abal ◽  
M. Velasco ◽  
J. Rubio ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Disease Status ◽  
Stage I ◽  
Stage Iii ◽  
Over Time

15024 Background: To determine whether the proportion of optimal disease status after surgery has changed along a defined period (the platinum era) on the setting of randomized clinical trials (RCT) in advanced ovarian cancer ( AOC). Methods: All RCT of chemotherapy for AOC in the platinum era (accrual period from 1980 to 2002) were searched. Studies were identified in an intensive review in MEDLINE, EMBASE and Cochrane Database, plus bibliographic references in the articles. We included those studies reporting stage, residual disease status and accruing both optimal and suboptimal disease. Simple linear regression models (slrm) were generated to evaluate the proportion of optimal disease status and of FIGO stages over time. Results are reported as two-side p values and 95% confidence intervals. Results: Seventy-five randomized studies, including 20,981 patients, fulfilled the inclusion criteria. Forty-two % of cases had optimal disease after surgery. Stage distribution was as follows: stage I-II, 7.5%, stage III, 72%, stage IV, 20%. Optimal disease status after surgery increased steadily over time, with larger proportions in more recent studies (r=.55; p < .005). Although there was a significant increase in stage I-II cases (r=.41; p < .005), inclusion of patients with stage III and stage IV did not change over time. Conclusions: Reported randomized clinical trials of chemotherapy for advanced ovarian cancer from 1980 to 2002 show a significant trend towards better postsurgical status of residual disease, with a larger proportion of patients with optimal disease in the more recent trials. This is marginally influenced by FIGO stage and therefore, occurs more likely from more extensive surgical debulking procedures. These changes in surgical approach result in an improvement of outcome, that may be independent of the postsurgical treatment used. No significant financial relationships to disclose.

Minimal Macroscopic Residual Disease (0.1–1 cm). Is It Still a Surgical Goal in Advanced Ovarian Cancer?

2016 ◽  
Vol 26 (5) ◽  
pp. 906-911 ◽  
Author(s):  
Luis M. Chiva ◽  
Teresa Castellanos ◽  
Sonsoles Alonso ◽  
Antonio Gonzalez-Martin
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Phase Iii ◽  
Stage Iii ◽  
Pubmed Database

ObjectiveThe objective of this review was to try to determine by searching in the literature what is the survival in patients with advanced ovarian cancer after a primary debulking with minimal macroscopic residual disease (MMRD; 0.1–10 mm). Additionally, this review aimed to explore the survival in patients with residual disease from 0.1 to 0.5 cm.MethodsA retrospective search was accomplished in the PubMed database looking for all English-language articles published between January 1, 2007 and December 31, 2014, under the following search strategy: “ovarian cancer and cytoreduction” or “ovarian cancer and phase III trial”. We selected those articles that contain information on both percentage of MMRD (0.1–1 cm) and median overall survival (OS) in this subset of patients with stage III to stage IV ovarian cancer after primary debulking surgery.ResultsThirteen publications were obtained including information of a total 11,999 patients with stage III to stage IV ovarian cancer. Five thousand thirty-seven patients (42%) had MMRD after the primary debulking (0.1–1 cm). Median overall survival in patients with MMRD was 40 months and disease-free survival (DFS) was 16 months. This group of patients obtained an advantage of 10 months in OS (40 vs 30 m) and 4 months in DFS (16 vs 12 m) compared with the group with suboptimal debulking (P < 0.001). Compared with the group of complete resection, patients with minimal macroscopic residuum showed a significant inferior median OS and DFS of 30 months and 14 months, respectively (OS, 70 vs 40 m; DFS, 30 vs 16 m) (P < 0.001). The group of residual disease of 0.1 to 0.5 cm reached a median survival of 53 months.ConclusionsPatients with ovarian cancer with MMRD after primary surgery obtain a modest but significant advantage in survival (10 months) over suboptimal patients. Patients with macroscopic residual disease (0.1–0.5 cm) obtain a better survival (53 months) than those with more than 0.5 to 1 cm. We propose that they should be classified as a different prognostic group.

scholarly journals Real-World Treatment Patterns, Survival, and Costs for Ovarian Cancer in Canada: A Retrospective Cohort Study Using Provincial Administrative Data

2021 ◽  
Vol 8 (2) ◽  
pp. 114-121
Author(s):  
Manjusha Hurry ◽  
Shazia Hassan ◽  
Soo Jin Seung ◽  
Ryan Walton ◽  
Ashlie Elnoursi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Health System ◽  
Advanced Disease ◽  
Stage Iv ◽  
Treatment Patterns ◽  
Stage I ◽  
Stage Iii ◽  
Advanced Stage ◽  
Poor Survival ◽  
Stage Disease

**Background:** In 2020, approximately 3100 Canadian women were diagnosed with ovarian cancer (OC), with 1950 women dying of this disease. Prognosis for OC remains poor, with 70% to 75% of cases diagnosed at an advanced stage and an overall 5-year survival of 46%. Current standard of care in Canada involves a combination of cytoreductive surgery and platinum-based chemotherapy. **Objective:** There are few studies reporting current OC costs. This study sought to determine patient characteristics and costs to the health system for OC in Ontario, Canada. **Methods:** Women diagnosed with OC in Ontario between 2010 and 2017 were identified. The cohort was linked to provincial administrative databases to capture treatment patterns, survival, and costs. Overall total and mean cost per patient (unadjusted) were reported in 2017 Canadian dollars, using a macro-based costing methodology called GETCOST. It is programmed to determine the costs of short-term and long-term episodes of health-care resources utilized. **Results:** Of the 2539 OC patients included in the study, the mean age at diagnosis was 60.4±11.35 years. The majority were diagnosed with stage III disease (n=1247). The only treatment required for 74% of stage I patients and 54% of stage II patients was first-line (1L) platinum chemotherapy; in advanced stages (III/IV) 24% and 20%, respectively, did not receive further treatment after 1L therapy. The median overall survival (mOS) for the whole cohort was 5.13 years. Survival was highest in earlier stage disease (mOS not reached in stage I/II), and dropped significantly in advanced stage patients (stage III: mOS=4.09 years; stage IV: mOS=3.47 years). Overall mean costs in patients stage I were CAD $58 099 compared to CAD $124 202 in stage IV. **Discussion:** The majority of OC patients continue to be diagnosed with advanced disease, which is associated with poor survival and increased treatment costs. Increased awareness and screening could facilitate diagnosis of earlier stage disease and reduce high downstream costs for advanced disease. **Conclusion:** Advanced OC is associated with poor survival and increased costs, mainly driven by hospitalizations or cancer clinic visits. The introduction of new targeted therapies such as olaparib could impact health system costs, by offsetting higher downstream costs while also improving survival.

scholarly journals Chemokine expression in patients with ovarian cancer or benign ovarian tumors

2021 ◽  
Author(s):  
Marek Nowak ◽  
Łukasz Janas ◽  
Malwina Soja ◽  
Ewa Głowacka ◽  
Krzysztof Szyłło ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adnexal Mass ◽  
Advanced Ovarian Cancer ◽  
Serum Levels ◽  
Ovarian Tumors ◽  
Benign Tumors ◽  
Significant Elevation ◽  
Chemiluminescence Method ◽  
Benign Ovarian Tumors ◽  
Potential Use

IntroductionChemokines play a crucial role in tumor growth and progression according to proangiogenic and immunosuppressive acting. This study was aimed to investigate the serum levels of selected chemokines in patients with ovarian cancer or benign ovarian tumors to point on their role in tumorigenesis and their potential use in preoperative diagnosing of adnexal mass.Material and methodsThe study group consisted of 59 women with ovarian cancer: 17 epithelial ovarian cancer (EOC) patients and 42 women with benign ovarian tumors. We measured in sera obtained preoperatively the level of CA125 and the panel of 5 chemokines: CX3CL1/Fractalkine, CXCL1/GRO-α, CXCL12/SDF-1, CCL20/MIP-3α and IL-17F, using chemiluminescence method with multiplexed bead based immunoassay.ResultsCX3CL1 was significantly elevated in sera of advanced ovarian cancer patients compared to women with benign ovarian tumors. The significant elevation of CXCL1 was also observed (both: early and advanced stage). The similar pattern was present with standard ovarian cancer marker – CA125. In our patients with endometriotic cysts CA125 levels were significantly higher than in women with other benign tumors whereas all analyzed chemokines had similar serum titers in patients with endometriotic vs other benign ovarian cysts.ConclusionsCX3CL1 and CXCL1 are elevated in sera of EOC patients what points on their role in cancer development. Moreover, they might be useful in preoperative differential diagnosis of ovarian tumors, especially as they were not elevated in cases of endometriosis.

Prognostic impact of neo-adjuvant vs adjuvant vs neo-adjuvant plus adjuvant chemotherapy in advanced ovarian cancer: Analysis of National Cancer Database.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5552-5552
Author(s):  
Suresh Mukkamala ◽  
Sukamal Saha ◽  
Sabarina Ramanathan ◽  
David Livert ◽  
Rajen Oza ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Bowel Resection ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
National Cancer Data Base ◽  
Stage Iii ◽  
Prognostic Impact ◽  
Chi Square ◽  
Cancer Data ◽  
In The Beginning

5552 Background: Patients (Pts) with advanced ovarian cancer (OvCa) are usually treated with primary debulking (deb) surgery (Sx) followed by adjuvant (adj) chemotherapy (CRx). Recently neo-adjuvant (neo-adj) CRx is increasingly being used to reduce the bulk of the tumor. Hence, we analyzed for any prognostic impact of neo-adj vs adj vs neo-adj plus adj CRx along with deb Sx in the management of advanced OvCa. Methods: Only Stage III and IV Pts in National Cancer Data Base (NCDB) from 2006-2014, who underwent deb Sx without bowel resection (1), with bowel resection (2) and with bowel and bladder resection (3) were analyzed. Group (gp) A Pts had neo-adj CRx, gp B had adj CRx and gp C Pts had neo-adj plus adj CRx. The Pearson Chi square testing was used to evaluate the survival between gp A vs B vs C. Results: A total of 20910 Pts in stage III and 7483 Pts in stage 4 were included. Stage III Pts had a better 5 year (yr) survival in gp B compared to gp A and C, in all Pts who underwent Sx 1, 2 and 3 (Table 1). Stage IV Pts had a better 5 yr survival in gp C compared to gp A and B who underwent Sx 1 and 2, and gp B had a better 5 yr survival in Pts who underwent Sx 3 (Table 1). Overall survival was worse for all stages in Pts with neo-adj ( gp A) than gp Band C. Conclusions: Deb Sx followed by adj CRx had better survival than in gp A or C. This may be secondary to less bulkier disease in the beginning in gp B than those in gp A or C requiring neo-adj CRx for the later. Pts survival also improved after addition of adj CRx following deb Sx compared to no adj CRx. A prospective multicenter randomized trial between each group may further validate the true benefits of neo-adj CRx in advanced OvCa. [Table: see text]

Prognostic implications of lymph node metastasis in advanced ovarian cancer: Analysis of National Cancer Database.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5567-5567
Author(s):  
Sukamal Saha ◽  
Sabarina Ramanathan ◽  
Suresh Mukkamala ◽  
Hayman S. Salib ◽  
Rajen Oza ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lymph Node ◽  
Bowel Resection ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Stage Iii ◽  
National Cancer Database ◽  
Group A ◽  
Prognostic Implications ◽  
Group B

5567 Background: During debulking surgery (Surg) for advanced ovarian cancer (OvCa), lymph node (LN) sampling are not routinely performed. Hence, prognostic implications of LN involvement following debulking surg and chemotherapy (ChemoRx) were analyzed from National Cancer Database (NCDB). Methods: Only Stage III and Stage IV patients (pts) from 2004 –2014 NCDB pts undergoing Debulking surg. and ChemoRx were included. Group A included pts with debulking surg without bowel resection; Group B with major bowel resection and Group C with bowel and bladder resection. Pts were further subdivided according to the use of 1) NeoAdjuvant (NeoAdj) 2) Adjuvant (Adj) and 3) Neo Adj and Adj ChemoRx. Survival analysis was done based on -ve or +ve LN status. using Pearson Chi Square testing. Results: Out of 10,737 Stage III and 3,102 Stage IV pts, there were 6828 Group A, 6413 Group B and 598 Group C pts. Five year overall survival (OS) for all pts in Stage III with LN-ve vs LN +ve was 59.9% vs 53.9% and Stage IV was 48.7% vs 41.2%. In Group A, B, and C, the 5 yr OS was better in LN – ve than LN +ve pts (Table1). The OS for both LN –ve and LN +ve groups were better in Adjuvant chemoRx in all 3 groups. OS was slightly better in Stage III vs Stage IV pts. Conclusions: Even though LN dissection are not routinely done during debulking surg, overall pts with LN metastasis do worse than LN –ve pts irrespective of the timing of ChemoRx. Hence, LN sampling during debulking surg should be strongly considered as it may provide important prognostic information. [Table: see text]

Neoadjuvant chemotherapy in advanced epithelial ovarian cancer: An institutional experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17044-e17044
Author(s):  
Kavitha Jain ◽  
Arun Chaturvedi ◽  
Sanjeev Misra ◽  
Vijay Kumar ◽  
Sameer Gupta ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Ovarian Carcinoma ◽  
Epithelial Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response To Therapy ◽  
Stage Iii ◽  
Gynecological Malignancy

e17044 Background: Epithelial ovarian cancer is the second most common gynecological malignancy among Indian women. Primary debulking surgery remains the standard of care in advanced operable ovarian cancer patients, but is associated with morbidity. Neoadjuvant chemotherapy followed by delayed primary cytoreductive surgery maybe a better treatment strategy in advanced ovarian cancer. We present our experience of neoadjuvant chemotherapy in advanced ovarian cancer with special emphasis on treatment outcomes. Methods: A retrospective analysis of advanced epithelial ovarian carcinoma (Stage IIIc and IV) patients treated at the Department of Surgical Oncology at King George’s Medical University, Lucknow between 2012 and 2017 was done. Results: A total of 151 patients with advanced ovarian carcinoma were treated during this period. Median age at diagnosis was 46 years. Among these patients, 137 underwent surgery, of which 59.1% were optimally cytoreduced. Papillary serous adenocarcinoma was the most common histological subtype (76.1%). Recurrence was seen in 79.3% patients, with a median time to recurrence 17 months (range 6.5 - 39 months). They were managed with second line chemotherapy and surgery. Median overall survival in this study for optimally cytoreduced stage III patients was 39 months and 18 months for optimally cytoreduced stage IV patients. Median progression free survival for stage III was 12 months and stage IV was 6 months. Conclusions: Neoadjuvant chemotherapy facilitates surgery in advanced ovarian cancer and helps in assessing chemotherapy responsiveness. It provides an opportunity to modify systemic treatment if there no response to therapy or disease progression.

Long-term survival and prognostic factors in advanced epithelial ovarian cancer with special emphasis upon the effects of protocol inclusion

1994 ◽  
Vol 4 (3) ◽  
pp. 180-187 ◽  
Author(s):  
K. Bertelsen ◽  
J. E. Andersen
Keyword(s):  
Ovarian Cancer ◽  
Performance Status ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Residual Tumor ◽  
Stage Iii ◽  
Prognostic Impact ◽  
Term Survival ◽  
Long Term Survival

The Danish Ovarian Cancer Study Group registered 722 patients in stages III and IV during the period 1981–1986. The material included 85% of all ovarian cancer patients in the catchment area of the group and patients allocated to protocol as well as patients treated outside protocols. Five and 10-year survival were: stage III 17%, and 8%, respectively; and stage IV 4% and 2%. Patients allocated to protocol had a significantly better survival than patients not included in protocols even when only patients younger than 70 years were compared. All non-protocol patients had a poorer prognosis irrespective of the reason for exclusion. Five-year survival for stage III protocol patients was 25% vs. 9%, for non-protocol patients younger than 70 years. The 10-year survival was 11% and 4% for stage III protocol and non-protocol patients, respectively. A multivariate analysis showed that residual tumor, age, stage, and performance status had prognostic value. In non protocol patients histologic grade had an additional marginal prognostic impact. In conclusion the study showed that the statement that long-term survival in advanced ovarian cancer has been increased could not be proven by comparison of survival from randomized studies performed in the early eighties with survival of stage III and IV patients before the introduction of cisplatinum chemotherapy. It is necessary to consider survival of all patients, protocol and non-protocol in a geographically well-defined region for evaluation of survival improvement.

Patterns of care for women with ovarian cancer in the United States.

1997 ◽  
Vol 15 (11) ◽  
pp. 3408-3415 ◽  
Author(s):  
K A Muñoz ◽  
L C Harlan ◽  
E L Trimble
Keyword(s):  
Ovarian Cancer ◽  
Older Women ◽  
Early Stage ◽  
Stage Iv ◽  
The United States ◽  
Stage I ◽  
Stage Iii ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Platinum Based Chemotherapy

PURPOSE To characterize treatments for ovarian cancer, to determine if recommended staging and treatment were provided, and to determine factors that influence receipt of recommended staging and treatment. METHODS A total of 785 women diagnosed with ovarian cancer in 1991 were selected from the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) program. Type and receipt of recommended staging and treatment were examined using data on surgery and physician-verified chemotherapy. RESULTS Most women with presumptive stage I and II ovarian cancer were treated with surgery alone (58%), while women with stage III or IV disease were treated with surgery plus platinum-based chemotherapy (75% stage III, 56% stage IV). Approximately 10% of women with presumptive stage I and II, 71% with stage III, and 53% with stage IV disease received recommended staging and treatment. The absence of lymphadenectomy and assignment of histologic grade were the primary reasons women with presumptive stage I and II cancer did not receive recommended staging and treatment, whereas for stages III and IV, it was due to older women not receiving surgery plus platinum-based adjuvant chemotherapy. Age, stage, comorbidity, "other" race/ethnicity, and treatment at a facility with an approved residency training program were associated with whether recommended staging and therapy were received. CONCLUSION Older women with late-stage disease did not receive recommended treatment. The majority of women with early-stage disease did not receive recommended staging and treatment.

Pathology of stage I versus stage III ovarian carcinoma with implications for pathogenesis and screening

2008 ◽  
Vol 18 (3) ◽  
pp. 465-469 ◽  
Author(s):  
A. V. YEMELYANOVA ◽  
J. A. COSIN ◽  
M. A. BIDUS ◽  
C. R. BOICE ◽  
J. D. SEIDMAN
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Screening Program ◽  
Ovarian Tumors ◽  
Stage I ◽  
Stage Iii ◽  
Advanced Stage ◽  
Ovarian Carcinomas ◽  
Pathologic Features ◽  
Abdominal Disease

The progression of ovarian carcinoma from stage I when it is confined to the ovaries and curable to disseminated abdominal disease, which is usually fatal, is poorly understood. An accurate understanding of this process is fundamental to designing, testing, and implementing an effective screening program for ovarian cancer. Pathologic features of the primary ovarian tumors in 41 FIGO stage I ovarian carcinomas were compared with those in 40 stage III carcinomas. The primary ovarian tumors in stage I cases, when compared with stage III, respectively, were significantly larger (15.4 versus 9.8 cm), were less frequently bilateral (12% versus 75%), more frequently contained a noninvasive component (88% versus 30%), had a higher proportion of a noninvasive component (42% versus 8%), and were more often nonserous (83% versus 20%) (P< 0.001 for all five comparisons). There are significant pathologic differences between the primary ovarian tumors in stage I and III ovarian carcinomas that are very difficult to explain by a simple temporal progression. These findings along with the growing body of literature suggest that early- and advanced-stage ovarian cancers are in many instances biologically different entities. This knowledge may have significant implications for our understanding of the biology of early- and advanced-stage ovarian cancer and therefore on the development of screening strategies for ovarian cancer.

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