Improved Classification of Epithelial Ovarian Cancer: Results of 3 Danish Cohorts

2011 ◽  
Vol 21 (9) ◽  
pp. 1592-1600 ◽  
Author(s):  
Karina Dahl Steffensen ◽  
Marianne Waldstrøm ◽  
Anni Grove ◽  
Bente Lund ◽  
Niels Pallisgård ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
P53 Protein ◽  
Benign Tumors ◽  
Braf Mutations ◽  
P53 Expression ◽  
Gynecology And Obstetrics

ObjectiveAn increasing body of evidence has suggested that epithelial ovarian cancer (EOC) patients can broadly be divided into 2 groups on the basis of histopathologic parameters and molecular profiles. Type 1 tumors are slow-growing tumors with inherent mutations such as KRAS or BRAF mutations, whereas type 2 tumors are more rapidly growing tumors of which many contain TP53 mutations. In the present study, we performed a comprehensive study in a large Danish material to evaluate the clinical importance.Materials and MethodsA total of 512 tissue samples were included (430 EOCs, 34 borderline, 28 benign tumors, and 20 normal ovaries). KRAS mutations (codon 12/13) and BRAF codon 600 mutations were analyzed from formalin-fixed paraffin-embedded tissue by ARMS qPCR. p53 expression was examined by immunohistochemistry.ResultsOf the EOC patients, 25% had histopathologically classified type 1 tumors, and of these, 44% were either KRAS or BRAF mutated. Of patients with histopathologic type 2 tumors, 66% showed p53 protein overexpression, whereas 4 (1.5%) patients contained a KRAS mutation. In a univariate survival analysis, a large difference in survival was seen between patients with type 1 and type 2 tumors. Patients with type histologic 2 tumors had significantly worse survival compared with patients with type 1 tumors (P< 10−5). International Federation of Gynecology and Obstetrics (FIGO) stage, tumor grade, residual tumor, and KRAS/BRAF mutation were independent predictors of overall survival in the multivariate analysis. Patients with KRAS/BRAF mutated carcinomas showed independent decreased overall survival with a hazard ratio of 2.01 (95% confidence interval, 1.13–3.57;P= 0.018).ConclusionsKRAS/BRAF mutations are with very few exceptions constrained to patients with histopathologic type 1 tumors, whereas p53 overexpression is very frequent in type 2 tumors. KRAS/BRAF mutations had independent prognostic importance. The classification presented here should have a major therapeutic implication and serve as a hallmark of future clinical trials.

Natural History of Stage IV Epithelial Ovarian Cancer

1999 ◽  
Vol 17 (3) ◽  
pp. 767-767 ◽  
Author(s):  
H. Bonnefoi ◽  
R. P. A'Hern ◽  
C. Fisher ◽  
V. Macfarlane ◽  
D. Barton ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Natural History ◽  
Epithelial Ovarian Cancer ◽  
Median Overall Survival ◽  
Response Rate ◽  
Residual Disease ◽  
Stage Iv ◽  
Therapeutic Implications ◽  
Gynecology And Obstetrics

PURPOSE: In this report we present the natural history, prognostic factors, and therapeutic implications of stage IV epithelial ovarian cancer (EOC). PATIENTS AND METHODS: We reviewed 192 patients with stage IV EOC as defined in 1985 by the International Federation of Gynecology and Obstetrics. RESULTS: The site of stage IV–defining disease was cytologically positive pleural effusion in 63 patients, liver in 50 patients, lymph nodes in 26 patients, lung in six patients, other sites in 15 patients, and disease at multiple stage IV–defining metastatic sites in 32 patients. Surgery was performed before chemotherapy in 169 patients; 25 patients (14.8%) were left with only microscopic residual disease or less than 2 cm of macroscopic residual disease. The overall response rate to chemotherapy was 56%; the complete response rate was 18%. The median progression-free survival was 7.1 months, and the median overall survival was 13.4 months. The median overall survival of patients with positive pleural effusions only was 13.4 months as compared with 10.5 months for patients with visceral disease only, but this difference was not statistically significant. The 5-year survival rate was 7.6%, with only six patients surviving more than 5 years. Univariate and multivariate analysis showed that two parameters were associated with a shorter survival time: visceral involvement (lung or liver) and diagnosis before 1984. CONCLUSION: Patients with stage IV EOC initially respond to chemotherapy as often as those with less advanced disease, but the long-term prognosis is very poor. The size of residual disease is not a prognostic factor in this group of patients, and, therefore, the role of debulking surgery in these patients needs to be reconsidered.

Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. London Gynaecological Oncology Group.

1998 ◽  
Vol 16 (7) ◽  
pp. 2426-2434 ◽  
Author(s):  
M Gore ◽  
P Mainwaring ◽  
R A'Hern ◽  
V MacFarlane ◽  
M Slevin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Total Dose ◽  
Single Agent ◽  
Dose Intensity ◽  
Hematologic Toxicity ◽  
Dose Increase ◽  
Gynecology And Obstetrics ◽  
Carboplatin Auc

PURPOSE We have examined the role of an increase in cisplatin dose-intensity in patients with advanced epithelial ovarian cancer by means of single-agent carboplatin therapy. PATIENTS AND METHODS Two hundred twenty-seven patients were randomized to treatment and eligible for analysis. The dose of carboplatin was calculated according to the Calvert formula. One hundred seventeen patients received carboplatin at an area under the concentration time curve (AUC) of 6 for six courses, administered every 28 days, and 110 patients received carboplatin at an AUC of 12 for four courses, administered every 28 days. Patients were eligible provided they had not received prior chemotherapy or radiotherapy and had International Federation of Gynecology and Obstetrics stages II to IV or relapsed stage I epithelial ovarian cancer. RESULTS The planned total-dose increase was 33% for the patients treated with carboplatin AUC 12, but the received percentage total-dose increase was 20%. There were no differences in progression-free or overall survival between the two treatment arms; the overall survival rate at 5 years was 31% and 34% of patients treated at AUCs 6 and 12, respectively. There was significantly more toxicity associated with carboplatin AUC 12, which resulted in more treatment delays and/or dose reductions (52% v 18%; P < .001). CONCLUSION We have shown that carboplatin can be delivered at an AUC of 12 for four courses without granulocyte colony-stimulating factor support, although significant hematologic toxicity occurs. Nonhematologic toxicities were not clinically significant. Carboplatin offers an opportunity to intensify cisplatin therapy, but a greater than two-fold increase in dose-intensity probably needs to be achieved before significant effects on survival will be produced and hematologic support will be required.

scholarly journals Detection of Human Cytomegalovirus in Patients with Epithelial Ovarian Cancer and its Impacts on Survival

2020 ◽  
Author(s):  
Min Yin ◽  
Aiping Chen ◽  
Fei Zhao ◽  
Xuechao Ji ◽  
Chuan Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Benign Tumors ◽  
Early Protein ◽  
Viral Carcinogenesis ◽  
Formalin Fixed Paraffin Embedded

Abstract Background: The cause of epithelial ovarian cancer(EOC) is not elucidated. Viral infection may induce chronic inflammatory infection and play a role in the pathogenesis of cancers. Some viruses are considered to be oncomodulatory, modulating cellular pathways such as cell proliferation, tumor progression, vascular disease development, and immune evasion. Human cytomegalovirus (HCMV) has been detected in several types of cancers including ovarian cancer. However, the role of HCMV in ovarian carcinogenesis remains controversial. Objective: To investigate the potential role of HCMV infection in EOC, we evaluated the prevalence of HCMV proteins in EOC tissue and its impacts on patients’ survival. Methods: Formalin-fixed, paraffin-embedded tissues from 66 patients with EOC and 30 patients with benign ovarian cystadenoma were studied. Specimens were detected for expression of HCMV immediate-early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry. Results: HCMV-IE protein expression was detected in 82% of EOC and 36% of benign tumors; pp65 was detected in 97% of EOC and 63% of benign tumors. Extensive expression of HCMV-IE protein was associated with higher stage of EOC. Reactivation of latent HCMV within the tumor at interval debulking surery may be induced by neoadjuvant chemotherapy before surgery. Extensive HCMV-IE expression was associated with shorter median overall survival than focal or negative expression (39 versus 41 months, P=0.03). Multivariate analysis indicated that HCMV-IE expression was an independent prognostic factor for overall survival (P = 0.034). Conclusions: This study demonstrate a high prevalence of HCMV proteins in tissue sections from patients with EOC. HCMV infection can be potential risk factor for EOC development. Extensive HCMV-IE expression indicated a poor prognosis. The relationship between HCMV and clinical outcomes highlight the need for further researches on the oncomodulatory of HCMV in ovarian cancer. Keywords: Epithelial ovarian cancer, Human cytomegalovirus, Viral carcinogenesis, Survival

scholarly journals Detection of Human Cytomegalovirus in Patients with Epithelial Ovarian Cancer and its Impacts on Survival

2020 ◽  
Author(s):  
Min Yin ◽  
Aiping Chen ◽  
Fei Zhao ◽  
Xuechao Ji ◽  
Chuan Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Protein Expression ◽  
Epithelial Ovarian Cancer ◽  
Human Cytomegalovirus ◽  
Hcmv Infection ◽  
Benign Tumors ◽  
Early Protein ◽  
Formalin Fixed Paraffin Embedded

Abstract Background: The cause of epithelial ovarian cancer(EOC) is not elucidated. Viral infection may induce chronic inflammatory infection and play a role in the pathogenesis of cancers. Some viruses are considered to be oncomodulatory, modulating cellular pathways such as cell proliferation, tumor progression, vascular disease development, and immune evasion. Human cytomegalovirus (HCMV) has been detected in several types of cancers including ovarian cancer. However, the role of HCMV in ovarian carcinogenesis remains controversial.Objective: To investigate the potential role of HCMV infection in EOC, we evaluated the prevalence of HCMV proteins in EOC tissue and its impacts on patients’ survival.Methods: Formalin-fixed paraffin-embedded tissues from 66 patients with EOC and 30 patients with benign ovarian cystadenoma were studied. Specimens were analyzed for expression of HCMV immediate early protein (IE) and HCMV tegument protein (pp65) by immunohistochemistry. Results: HCMV-IE protein expression was detected in 82% of EOC and 36% of benign tumors; pp65 was detected in 97% of EOC and 63% of benign tumors. Extensive HCMV-IE protein expression was associated with higher stage of EOC. Reactivation of latent HCMV within the tumor at interval debulking surgery may be induced by neoadjuvant chemotherapy before surgery. Extensive HCMV-IE expression was associated with shorter median overall survival than focal or negative expression (39 versus 41 months, P=0.03). Multivariate analysis indicated that HCMV-IE expression was an independent prognostic factor for overall survival (P = 0.034). Conclusions: This study demonstrate a high prevalence of HCMV proteins in tissue sections from patients with EOC. HCMV infection can be potential risk factor for EOC development. Extensive HCMV-IE expression indicated a poor prognosis. The relationship between HCMV and clinical outcomes highlight the need for further researches on the oncomodulatory role of HCMV in ovarian cancer.

Prognostic significance of the controlling nutritional status (CONUT) score in epithelial ovarian cancer

2019 ◽  
Vol 30 (1) ◽  
pp. 74-82
Author(s):  
Yong Li ◽  
Can Zhang ◽  
Rui Ji ◽  
Hong Lu ◽  
Weiling Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Nutritional Status ◽  
Epithelial Ovarian Cancer ◽  
Prognostic Significance ◽  
Rank Test ◽  
Gynecology And Obstetrics ◽  
Pre Treatment ◽  
Conut Score

PurposeThe controlling nutritional status (CONUT) score is a nutritional indicator that serves as a prognostic factor for many malignancies. This study aimed to investigate the prognostic significance of pre-treatment CONUT scores in patients with epithelial ovarian cancer.MethodsWe evaluated newly diagnosed patients with epithelial ovarian cancer who were treated at the Nantong Tumor Hospital, between January 2013 and April 2016. Pre-treatment CONUT scores were calculated using serum albumin levels, total lymphocyte counts, and cholesterol levels. The optimal CONUT score cut-off was determined via receiver operating characteristic curve and Youden’s index. The difference in survival rates between the high-CONUT score group and the low-CONUT score group was analyzed using Kaplan-Meier curves and the log-rank test. Univariate and multivariate Cox proportional hazard regression models were used to identify prognostic factors influencing survival in these patients.ResultsIn total, 206 patients were included. The optimal cut-off value for the CONUT score was 3. The high-CONUT score group (score ≥3) had higher International Federation of Gynecology and Obstetrics (FIGO) stages, medium-large amounts of ascitic fluid, higher CA125 levels, and more chemoresistance than those with a low-CONUT score (score <3). The low-CONUT score group had longer median overall survival (64.8 vs 32.3 months, respectively; p<0.001) and longer median progression-free survival (32.3 vs 18.8 months, respectively; p=0.002) than those in the high-CONUT score group. Multivariate analysis showed that the CONUT score was an independent prognostic factor for overall survival.ConclusionsThe CONUT score predicts the prognosis of epithelial ovarian cancer and is thus helpful for individualizing treatment and improving survival in these patients.

Immune Response Evaluation Through Determination of Type 1, Type 2, and Type 17 Patterns in Patients With Epithelial Ovarian Cancer

2012 ◽  
Vol 20 (7) ◽  
pp. 828-837 ◽  
Author(s):  
Eduardo Batista Cândido ◽  
Luciana Maria Silva ◽  
Andréa Teixeira Carvalho ◽  
Rívia Mara Lamaita ◽  
Roberto Mundim Porto Filho ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Epithelial Ovarian Cancer ◽  
Response Evaluation

scholarly journals Trace Amine-Associated Receptor 1 (TAAR1) Is a Positive Prognosticator for Epithelial Ovarian Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8479
Author(s):  
Tilman L. R. Vogelsang ◽  
Aurelia Vattai ◽  
Elisa Schmoeckel ◽  
Till Kaltofen ◽  
Anca Chelariu-Raicu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Tnm Classification ◽  
Rank Correlation ◽  
University Hospital ◽  
Cancer Tissue ◽  
Low Grade ◽  
High Grade ◽  
Trace Amine

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.

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