scholarly journals Clear cell carcinoma of the ovary: a clinical and molecular perspective

2020 ◽  
pp. ijgc-2020-001656
Author(s):  
Yasushi Iida ◽  
Aikou Okamoto ◽  
Robert L Hollis ◽  
Charlie Gourley ◽  
C Simon Herrington
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Early Stage ◽  
Molecular Characteristics ◽  
Specific Gene ◽  
Tumor Type ◽  
Early Stage Disease ◽  
Platinum Based Chemotherapy ◽  
Carcinoma Of The Ovary

Clear cell carcinoma of the ovary has distinct biology and clinical behavior. There are significant geographical and racial differences in the incidence of clear cell carcinoma compared with other epithelial ovarian tumors. Patients with clear cell carcinoma are younger, tend to present at an early stage, and their tumors are commonly associated with endometriosis, which is widely accepted as a direct precursor of clear cell carcinoma and has been identified pathologically in approximately 50% of clear cell carcinoma cases. The most frequent and important specific gene alterations in clear cell carcinoma are mutations of AT-rich interaction domain 1A (ARID1A) (~50% of cases) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (~50% cases). More broadly, subgroups of clear cell carcinoma have been identified based on C-APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) and C-AGE (age-related) mutational signatures. Gene expression profiling shows upregulation of hepatocyte nuclear factor 1-beta (HNF1β) and oxidative stress-related genes, and has identified epithelial-like and mesenchymal-like tumor subgroups. Although the benefit of platinum-based chemotherapy is not clearly defined it remains the mainstay of first-line therapy. Patients with early-stage disease have a favorable clinical outcome but the prognosis of patients with advanced-stage or recurrent disease is poor. Alternative treatment strategies are required to improve patient outcome and the development of targeted therapies based on molecular characteristics is a promising approach. Improved specificity of the histological definition of this tumor type is helping these efforts but, due to the rarity of clear cell carcinoma, international collaboration will be essential to design appropriately powered, large-scale clinical trials.

Gynecologic Cancer InterGroup (GCIG) Consensus Review for Clear Cell Carcinoma of the Ovary

2014 ◽  
Vol 24 (Supp 3) ◽  
pp. S20-S25 ◽  
Author(s):  
Aikou Okamoto ◽  
Rosalind M. Glasspool ◽  
Seiji Mabuchi ◽  
Noriomi Matsumura ◽  
Hiroyuki Nomura ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Early Stage ◽  
Gynecologic Cancer ◽  
Phase Iii ◽  
Histologic Subtype ◽  
Phase Iii Study ◽  
Dual Inhibitors ◽  
Carcinoma Of The Ovary

AbstractClear cell carcinoma of the ovary (CCC) is a histologic subtype of epithelial ovarian cancer with a distinct clinical behavior. There are marked geographic differences in the prevalence of CCC. The CCC is more likely to be detected at an early stage than high-grade serous cancers, and when confined within the ovary, the prognosis is good. However, advanced disease is associated with a very poor prognosis and resistance to standard treatment. Cytoreductive surgery should be performed for patients with stage II, III, or IV disease. An international phase III study to compare irinotecan/cisplatin and paclitaxel/carboplatin as adjuvant chemotherapy for stage IIV CCC has completed enrollment (GCIG/JGOG3017). Considering the frequent PIK3CA mutation in CCC, dual inhibitors targeting PI3K, AKT in the mTOR pathway, are promising. Performing these trials and generating the evidence will require considerable international collaboration.

Significance of Ovarian Endometriosis on the Prognosis of Ovarian Clear Cell Carcinoma

2018 ◽  
Vol 28 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Jeong-Yeol Park ◽  
Dae-Yeon Kim ◽  
Dae-Shik Suh ◽  
Jong-Hyeok Kim ◽  
Yong-Man Kim ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Early Stage ◽  
Stage I ◽  
Ovarian Clear Cell Carcinoma ◽  
Ovarian Endometriosis ◽  
Early Stage Disease ◽  
Group 2 ◽  
Group 1

IntroductionThe aim of this study was to evaluate the significance of ovarian endometriosis on the prognosis of ovarian clear cell carcinoma (OCCC).MethodsPatients with OCCC were divided into 2 groups according to the presence of ovarian endometriosis: group 1, no coexisting ovarian endometriosis; group 2, clear cell carcinoma arising from ovarian endometriosis or the presence of ovarian endometriosis elsewhere in the ovary. Clinicopathologic characteristics, disease-free survival (DFS), and overall survival (OS) were compared between the 2 groups.ResultsOf 155 patients with OCCC, 77 were categorized into group 1 and 78 into group 2. Group 2 patients were younger than group 1 (median age, 48 vs 51 years; P = 0.005) and had higher incidence of early-stage disease (stage I, 77% vs 58%; P = 0.001) and lower incidence of lymph node metastasis (4% vs 17%; P = 0.008). Group 2 patients were observed to have a significantly higher 5-year DFS (P < 0.001) and OS (P = 0.001) compared with group 1. In stage I disease, group 2 had a significantly higher 5-year DFS (P = 0.004) and OS (P = 0.016) than did group 1. In the multivariate analysis, coexisting endometriosis and advanced International Federation of Obstetrics and Gynecology stage were significant factors for both DFS and OS rates.ConclusionsOvarian clear cell carcinoma with endometriosis was found more frequently in younger women and had a higher incidence of early-stage disease and a lower incidence of lymph node metastasis compared with OCCC without endometriosis. Ovarian endometriosis was associated with improved prognostic factors and a better DFS and OS even in stage I disease. Ovarian endometriosis was an independent prognostic factor for OCCC.

Clear Cell Carcinoma of the Ovary: A Distinct Histologic Type with Poor Prognosis and Resistance to Platinum-Based Chemotherapy in Stage III Disease

1996 ◽  
Vol 60 (3) ◽  
pp. 412-417 ◽  
Author(s):  
Barbara A. Goff ◽  
Ricardo Sainz de la Cuesta ◽  
Howard G. Muntz ◽  
Deborah Fleischhacker ◽  
Marit Ek ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Stage Iii ◽  
Histologic Type ◽  
Platinum Based Chemotherapy ◽  
Carcinoma Of The Ovary

scholarly journals The Frequency and Clinical Implication of Mismatch Repair Protein Deficiency in Chinese Patients with Ovarian Clear Cell Carcinoma

2021 ◽  
Author(s):  
Shuang Ye ◽  
Shuling Zhou ◽  
Siyuan Zhong ◽  
Boer Shan ◽  
Wenhua Jiang ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Mismatch Repair ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Early Stage ◽  
Progression Free Survival ◽  
Chinese Patients ◽  
Ovarian Clear Cell Carcinoma ◽  
Early Stage Disease ◽  
Platinum Sensitive

Abstract Background: To assess the prevalence of deficient mismatch repair (MMR) in Chinese ovarian clear cell carcinoma (CCC) patients and its association with clinicopathologic features.Methods: Immunohistochemistry with four antibodies against MLH1, PMS2, MSH2 and MSH6 were performed on whole section slides. Results were correlated with clinicopathologic variables.Results: A total of 108 cases were included in the study, with a median age of 52 years at first diagnosis. Early-stage disease and platinum-sensitive recurrence accounted for 62.3% and 69.6%, respectively. Overall, the estimated 5-year overall survival was 70.3% and 20.7% in patients with early and late stage tumor, respectively. Deficient MMR were identified in 5.6% (6/108) of the cohort and included MSH2/MSH6 (n=4) and MLH1/PMS2 (n=2). The average age of the six patients was 45.6 years. The rate of MMR-deficient tumors in women ≤ 50 years was relatively higher than that those over 50 years (10.0% Vs. 2.9%; P=0.266). A half of the patients with deficient MMR were diagnosed with a synchronous (endometrial or colorectal) and metachronous (endometrial) cancer, significantly more than those intact counterparts (P=0.002). All the six patients had early-stage tumor and the majority (83.3%) were platinum-sensitive. The median progression-free survival was slightly higher in patients with defective MMR expression than those intact counterparts (30 months Vs. 27 months), although significance was not achieved (P=0.471). Conclusions: Ovarian CCC patients with young age and concurrent diagnosis of endometrial and colorectal cancer are more likely to have MMR-deficient tumors. It merits further evaluation whether patients harboring MMR abnormality has favorable prognosis.

Glypican-3 expression predicts poor clinical outcome of patients with early-stage clear cell carcinoma of the ovary

2010 ◽  
Vol 63 (11) ◽  
pp. 962-966 ◽  
Author(s):  
T. Umezu ◽  
K. Shibata ◽  
H. Kajiyama ◽  
E. Yamamoto ◽  
A. Nawa ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Early Stage ◽  
Poor Clinical Outcome ◽  
Carcinoma Of The Ovary

scholarly journals The Clinical Characteristics and Treatment Results in the Patients with Clear Cell Carcinoma of the Ovary

2021 ◽  
Vol 4 (4) ◽  
pp. 01-08
Author(s):  
Chul Kim
Keyword(s):  
Cell Carcinoma ◽  
Clinical Characteristics ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Figo Stage ◽  
Stage I ◽  
Stage Iii ◽  
Treatment Results ◽  
Platinum Based Chemotherapy ◽  
Carcinoma Of The Ovary

Background: It is well known that clear cell carcinoma of the ovary (CCC) demonstrates different clinical behaviors from other epithelial ovarian cancer and has strong association with endometriosis, thromboembolic complication, hypercalcemia, and large pelvic mass. The introduction of cisplatin-based chemotherapy significantly changed the postoperative management of ovarian cancer patients. Different studies showed a better response rate of CCC to chemotherapy with paclitaxel plus carboplatin regime than with the conventional platinum-based regimens. Aim: The purpose of this study was to evaluate the patients’ clinical characteristics and treatment results for clear cell carcinoma (CCC) of the ovary treated in paclitaxel-platinum chemotherapy in comparison with those treated in conventional platinum-based chemotherapy after primary surgery Methods: We retrospectively reviewed the medical records of 40 patients with CCC who received treatment in the department of obstetrics and gynecology, Samsung Medical Center from March, 1996 to April 2006. The clinical characteristics, treatment results and follow-up data were collected from medical records and/or telephone surveys. Results: Mean age was 47 years (range 30–72 years). Patients with age less than 50years were 62.5%. Tumors were 15% (6/40) stage IA, 2.5% (1/40) stage IB, 37.5% (15/40) stage IC, 5% (2/40) stage II, 32.5% (13/40) stage III, and 7.5% (3/40) stage IV. Patients with CCC were more likely to have FIGO stage I & II disease than FIGO stage III & IV (60% vs. 40%). Five-year progression-free survival and overall survival were 91% and 80% in stage I & II, 36% and 55% in stage III & IV, respectively (5-yr PFS; P<0.01, 5-yr OS; P=0.03). With a median follow-up of 45 months (2-112 months), 75% (18/24) of stage I/II patients are alive, while 19% (3/16) of stage III/IV patients are alive. 37.5% (15/40) of the patients presented with endometriosis. Except for one patient who was referred by a local clinic, all patients underwent cytoreductive surgery. The rate of optimal debulking (≤ 1cm residual tumor diameter) was 90% (36/40). Overall, for women treated with platinum-based chemotherapy, 75% (27/36) had clinically complete responses to adjuvant chemotherapy. But there was no survival benefit according to chemotherapeutic differences in the patients who received cytoreductive surgery followed between conventional platinum-based chemotherapy (CAP or CP) and by paclitaxel and platinum-based chemotherapy (P=0.40). Univariate analysis showed that stage was the only favorable prognostic factor for women with clear cell carcinoma of the ovary (P=0.04). Conclusions: Our results suggest that CCC has a distinct clinical behavior, similar to previous studies, that frequently presents at early- stages and is associated with endometriosis. In addition, there was a close correlation between the level of CA-125 and survival, and there was no survival benefit according to chemotherapeutic differences. 〔CAP (CP) VS TP(TC)〕

Uterine Clear Cell Carcinoma: Does Adjuvant Chemotherapy Improve Outcomes?

2016 ◽  
Vol 27 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Julie M.V. Nguyen ◽  
Geneviève Bouchard-Fortier ◽  
Marcus Q. Bernardini ◽  
Eshetu G. Atenafu ◽  
Guangming Han ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Early Stage ◽  
Stage I ◽  
High Rate ◽  
Advanced Stage ◽  
Early Stage Disease ◽  
Uterine Clear Cell Carcinoma

ObjectivesWomen with uterine clear cell carcinoma (UCCC) are at high risk of relapse. Adjuvant chemotherapy (CT) is often recommended, although its effectiveness remains controversial. Our objective was to evaluate treatment-related outcomes of patients with UCCC, particularly those treated with adjuvant CT.MethodsIn this retrospective cohort study, patients diagnosed with UCCC at 2 academic cancer centers from 2000 to 2014 were included. Clinical, surgical, and pathological data were collected. Survival estimates were obtained using the Kaplan-Meier method and compared by log rank test. Multivariable analysis was used to determine the effect of CT and radiation therapy (RT) on overall survival (OS) and progression-free survival (PFS).ResultsWe included 146 patients with UCCC, with a median follow-up of 27 months (range, 1–160). Ninety-five (65%) patients presented with stage I to II disease and 51 (35%) with stage III to IV disease. Forty-six percent of patients with clinical stage I were upstaged after surgery: 29% were upstaged to stages III and IV. Thirty-one percent of patients with early-stage disease and 70% with advanced-stage received CT. Among recurrences, the majority had distant relapse in both early-stage (61.5%) and advanced-stage (96.3%) diseases. In both patients with early-stage and advanced-stage diseases, adjuvant CT did not improve OS or PFS. On multivariate analysis, CT was not a significant factor associated with improved PFS (hazard ratio [HR], 1.37; 95% confidence interval [CI], 0.69–2.71;P= 0.37) or OS (HR, 0.58; 95% CI, 0.24–1.38;P= 0.22), whereas RT was associated with improved PFS (HR, 0.51; 95% CI, 0.29–0.90;P= 0.02) and OS (HR, 0.19; 95% CI, 0.09–0.42;P< 0.001).ConclusionsThe high rate of upstaging after surgery highlights the importance of lymph node assessment. The high rate of distant recurrence questions the effectiveness of current CT regimens and warrants the development of novel systemic approaches. The role of adjuvant RT deserves further study.

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