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

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.

2021 ◽  
Vol 8 (2) ◽  
pp. 114-121
Author(s):  
Manjusha Hurry ◽  
Shazia Hassan ◽  
Soo Jin Seung ◽  
Ryan Walton ◽  
Ashlie Elnoursi ◽  
...  

**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.


2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 147-151 ◽  
Author(s):  
F. De Smet ◽  
N. L.M.M. Pochet ◽  
K. Engelen ◽  
T. Van Gorp ◽  
P. Van Hummelen ◽  
...  

We investigated whether prognostic information is reflected in the expression patterns of ovarian carcinoma samples. RNA obtained from seven FIGO stage I without recurrence, seven platin-sensitive advanced-stage (III or IV), and six platin-resistant advanced-stage ovarian tumors was hybridized on a complementary DNA microarray with 21,372 spotted clones. The results revealed that a considerable number of genes exhibit nonaccidental differential expression between the different tumor classes. Principal component analysis reflected the differences between the three tumor classes and their order of transition. Using a leave-one-out approach together with least squares support vector machines, we obtained an estimated classification test accuracy of 100% for the distinction between stage I and advanced-stage disease and 76.92% for the distinction between platin-resistant versus platin-sensitive disease in FIGO stage III/IV. These results indicate that gene expression patterns could be useful in clinical management of ovarian cancer.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17536-e17536
Author(s):  
Snezhanna Gening ◽  
Tatyana Abakumova ◽  
Tatyana Gening

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]


2019 ◽  
Vol 65 (1) ◽  
pp. 56-62
Author(s):  
Alisa Villert ◽  
Larisa Kolomiets ◽  
Natalya Yunusova ◽  
Yevgeniya Fesik

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.


2003 ◽  
Vol 21 (15) ◽  
pp. 2849-2855 ◽  
Author(s):  
Mahesh A. Varia ◽  
Frederick B. Stehman ◽  
Brian N. Bundy ◽  
Jo Ann Benda ◽  
Daniel L. Clarke-Pearson ◽  
...  

Purpose: The objectives of this prospective randomized study of consolidation therapy were to evaluate recurrence-free survival (RFS), overall survival (OS), and the morbidity of intraperitoneal (IP) chromic phosphate suspension (32P) therapy in patients with stage III epithelial ovarian carcinoma who have no detectable evidence of disease at the second-look laparotomy (SLL) procedure after primary chemotherapy. Patients and Methods: In a multi-institution clinical cooperative trial, 202 eligible patients with a negative SLL were randomly selected to receive either 15 mCi IP 32P (n = 104) or no further therapy (NFT; n = 98). Results: With a median follow-up of 63 months in living patients, 68 patients in the IP 32P group (65%) and 63 patients in the NFT group (64%) have developed tumor recurrence. The relative risk of recurrence is 0.90 (IP 32P to NFT) (90% confidence interval [CI], 0.68 to 1.19). The 5-year RFS rate is 42% and 36% for the IP 32P and NFT groups, respectively; the difference is not statistically significant (log-rank test, P = .27). There was no statistically significant difference in OS (P = .19). The relative risk of death is 0.85 (IP 32P to NFT) (90% CI, 0.62 to 1.16). Sixteen patients (8%) experienced grade 3 or 4 adverse effects, with eight in each respective group. Conclusion: Intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after a negative SLL. Despite complete pathologic remission at SLL after initial surgery and platinum-based chemotherapy, 61% of stage III ovarian cancer patients had tumor recurrence within 5 years of negative SLL. This indicates a need for more effective initial therapy and further studies of consolidation therapy.


2018 ◽  
Vol 28 (5) ◽  
pp. 915-924 ◽  
Author(s):  
Jennifer J. Mueller ◽  
Henrik Lajer ◽  
Berit Jul Mosgaard ◽  
Slim Bach Hamba ◽  
Philippe Morice ◽  
...  

ObjectiveWe sought to describe a large, international cohort of patients diagnosed with primary mucinous ovarian carcinoma (PMOC) across 3 tertiary medical centers to evaluate differences in patient characteristics, surgical/adjuvant treatment strategies, and oncologic outcomes.MethodsThis was a retrospective review spanning 1976–2014. All tumors were centrally reviewed by an expert gynecologic pathologist. Each center used a combination of clinical and histologic criteria to confirm a PMOC diagnosis. Data were abstracted from medical records, and a deidentified dataset was compiled and processed at a single institution. Appropriate statistical tests were performed.ResultsTwo hundred twenty-two patients with PMOC were identified; all had undergone primary surgery. Disease stage distribution was as follows: stage I, 163 patients (74%); stage II, 8 (4%); stage III, 40 (18%); and stage IV, 10 (5%). Ninety-nine (45%) of 219 patients underwent lymphadenectomy; 41 (19%) of 215 underwent fertility-preserving surgery. Of the 145 patients (65%) with available treatment data, 68 (47%) had received chemotherapy—55 (81%) a gynecologic regimen and 13 (19%) a gastrointestinal regimen. The 5-year progression-free survival (PFS) rates were 80% (95% confidence interval [CI], 73%–85%) for patients with stage I to II disease and 17% (95% CI, 8%–29%) for those with stage III to IV disease. The 5-year PFS rate was 73% (95% CI, 50%–86%) for patients who underwent fertility-preserving surgery.ConclusionsMost patients (74%) presented with stage I disease. Nearly 50% were treated with adjuvant chemotherapy using various regimens across institutions. The PFS outcomes were favorable for those with early-stage disease and lower but acceptable for those who underwent fertility preservation.


2005 ◽  
Vol 15 (2) ◽  
pp. 217-223 ◽  
Author(s):  
V. Loizzi ◽  
G. Cormio ◽  
L. Resta ◽  
C. A. Rossi ◽  
A. R. Di Gilio ◽  
...  

The aim of this study was to compare the outcome of patients with advanced ovarian carcinoma treated with neoadjuvant chemotherapy (NACT) with those treated conventionally with primary debulking surgery. From 1994 to 2003, all consecutive cases of advanced-stage epithelial ovarian carcinoma treated with NACT at the University of Bari were identified. A well-balanced group of women who underwent primary debulking surgery followed by platinum-based chemotherapy was selected as controls. Kaplan–Meier and Cox proportional hazards analyses were used to determine the predictors for survival. Thirty women with advanced-stage epithelial ovarian carcinoma were treated with NACT and compared to 30 patients who underwent primary debulking surgery. Patients in the NACT were significantly older and had a poorer performance status compared to the controls. However, no statistical difference was observed in overall disease-specific survival (P = 0.66) and disease-free survival (P = 0.25) between the two groups. Although patients in the NACT group are significantly older and have a poorer performance status, this treatment modality does not compromise survival. Prospective randomized trials comparing NACT to conventional treatment to determine the quality of life and cost/benefit outcomes are now appropriate for women presenting advanced epithelial ovarian cancer.


2003 ◽  
Vol 19 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Cristina Rodríguez-Burford ◽  
David C. Chhieng ◽  
Cecil R. Stockard ◽  
Marc J. Kleinberg ◽  
Mack N. Barnes ◽  
...  

Ovarian cancer has a high mortality rate largely due to the limited number of ovarian carcinomas detected at an early stage. Understanding the molecular changes occurring during the progression of ovarian carcinoma would aid in the development of therapies that may inhibit or target metastasis. Primary and metastatic lesions from 54 and 40 patients with advanced ovarian carcinoma, respectively (including matched primary and metastatic lesions from 30 patients) were evaluated for nuclear accumulation of p53 (clone BP53-12-1) and cytoplasmic and membranous immunostaining of p185 erbB-2 (clone 3B5) by immunohistochemistry. No differences in the immunostaining of p53 and p185erbB-2 (cytoplasm or membrane) were observed between primary and metastatic lesions of the matched cases. Similarly, no differences in the proportion of positive cases of p53 between primary and metastatic lesions of the matched cases was observed. Thus, novel therapies that target p53 or p185erbB-2 can utilize specimens from either primary or metastatic lesions to characterize these targets prior to therapy. Spearman correlations between p53 and p185erbB-2 (cytoplasm or membrane) immunohistochemistry scores were insignificant for the matched cases, all primary lesions, and all metastatic lesions. Also, no significant associations occurred between nuclear accumulation of p53 (positive versus negative) and phenotypic expression of p185erbB-2 (cytoplasm or membrane) immunostaining scores for the matched cases, all primary lesions, and all metastatic lesions. Thus, the nuclear accumulation of p53 and immunostaining of p185erbB-2 in the cytoplasm or on the cellular membranes are independent.


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