Prognostic significance of tumor laterality in advanced ovarian cancer

PURPOSE: To investigate the prognostic and predictive relevance of p53, Mdm2, and Bcl-2 protein expression in advanced ovarian cancer. PATIENTS AND METHODS: Tumor biopsy specimens from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for expression of p53, Mdm2, and Bcl-2 proteins. Both uni- and multivariate analyses of prognostic factors were performed, and correlations with classical clinicopathologic parameters and response to chemotherapy were examined. RESULTS: Forty-nine percent and 39% of cases were considered positive for expression of p53 and Bcl-2, respectively. p53 expression was correlated with loss of histologic differentiation and Bcl-2 expression with smaller residual disease after primary surgery. The absence of p53 expression and the presence of Bcl-2 expression were associated with improved survival but not with overall response to chemotherapy, although a positive correlation was found between Bcl-2 expression and the possibility of obtaining a completely negative second-look laparotomy. Expression of Mdm2 was found in 17% of cases. Although correlations were found with known favorable clinicopathologic factors, no prognostic significance was demonstrated for Mdm2 in this patient group. In multivariate analyses, histologic type, degree of differentiation, residual disease, and p53 alone or combined with Bcl-2 expression were found to be independently associated with overall survival. CONCLUSION: p53, and especially the combination of p53 and Bcl-2 expression data, represents an independent prognostic predictor in stage III ovarian cancer. Despite their role in the apoptotic process, p53 and Bcl-2 do not seem to be clinically useful predictors of response to combination chemotherapy in these patients.

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Prognostic Significance of Systematic Lymphadenectomy in Patients With Optimally Debulked Advanced Ovarian Cancer: A Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2020.00086 ◽

2020 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Yizi Wang ◽

Fang Ren ◽

Zixuan Song ◽

Xiaoying Wang ◽

Chiyuan Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

Meta Analysis ◽

Prognostic Significance ◽

Advanced Ovarian Cancer ◽

Systematic Lymphadenectomy

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Prognostic significance of systematic lymphadenectomy as part of primary debulking surgery in patients with advanced ovarian cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2012.05.014 ◽

2012 ◽

Vol 126 (3) ◽

pp. 381-386 ◽

Cited By ~ 26

Author(s):

Suk-Joon Chang ◽

Robert E. Bristow ◽

Hee-Sug Ryu

Keyword(s):

Ovarian Cancer ◽

Prognostic Significance ◽

Advanced Ovarian Cancer ◽

Debulking Surgery ◽

Systematic Lymphadenectomy ◽

Primary Debulking Surgery

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Expression of Apoptosis-Related Proteins Is an Independent Determinant of Patient Prognosis in Advanced Ovarian Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.22.3775 ◽

2000 ◽

Vol 18 (22) ◽

pp. 3775-3781 ◽

Cited By ~ 40

Author(s):

M. Baekelandt ◽

R. Holm ◽

J.M. Nesland ◽

C.G. Tropé ◽

G.B. Kristensen

Keyword(s):

Ovarian Cancer ◽

Residual Disease ◽

Prognostic Significance ◽

Advanced Ovarian Cancer ◽

Disease Status ◽

Stage Iii ◽

Expression Data ◽

Response To Chemotherapy ◽

Independent Prognostic Significance ◽

Related Proteins

PURPOSE: The present study was undertaken to investigate the prognostic and predictive relevance of the expression of apoptosis-related proteins Bax, Bcl-XL, and Mcl-1 in advanced ovarian cancer. PATIENTS AND METHODS: Tumor biopsies from 185 consecutive and homogeneously treated patients with stage III ovarian cancer were examined immunohistochemically for the expression of Bax, Bcl-XL and Mcl-1 proteins. Their prognostic relevance was examined in a uni- and multivariate survival analysis. RESULTS: Sixty-six percent of cancer cases expressed Bax, 62% Bcl-XL, and 53% Mcl-1. The expression of Bax correlated with tumor differentiation (P = .016) and less residual disease after surgery (P < .0001). In univariate analysis, Bax expression was associated with improved (P = .0004) prognosis and Mcl-1 expression with poorer (P = .011) prognosis. None of the factors studied was of independent prognostic significance by itself, but when Bax and Bcl-2 expression data were considered together, this combined variable was of independent prognostic significance (P = .0115), together with residual disease status (P = .0016), differentiation grade (P = .0014), and the presence of ascites (P = .0122). Patients with a long median survival (104 months) could be discriminated from those with a short one (16 months) by combining the individual patients’ expression data for p53, Bax, and Bcl-2 with their residual disease status (P < .00001). None of the factors studied was able to predict response to chemotherapy. CONCLUSION: The expression of selected apoptosis-related proteins is of independent prognostic significance and may be helpful in a molecular substaging of patients with stage III ovarian cancer.

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Venous thromboembolism in advanced ovarian cancer patients undergoing front-line adjuvant chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5570 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5570-5570

Author(s):

Alok Pant ◽

Julian C. Schink

Keyword(s):

Ovarian Cancer ◽

Venous Thromboembolism ◽

Adjuvant Chemotherapy ◽

Epithelial Ovarian Cancer ◽

Bowel Resection ◽

Prognostic Significance ◽

Advanced Ovarian Cancer ◽

Ca 125 ◽

Front Line ◽

Advanced Epithelial Ovarian Cancer

5570 Background: To define the incidence and prognostic significance of venous thromboembolism (VTE) in patients with advanced, epithelial ovarian cancer undergoing front-line adjuvant chemotherapy after extended period (28 day) post-operative prophylaxis. Methods: A retrospective analysis of patients with advanced, epithelial ovarian cancer who underwent surgery and chemotherapy at a single institution from January 2008 through December 2011 was performed. Exclusion criteria were prior history of VTE, VTE during the post-operative period, clear cell histology, use of anti-coagulation for a different indication, and lack of compliance with 28 days of post-operative prophylaxis with a low molecular weight heparin. Results: 128 patients met criteria for inclusion. Sixteen patients had a reported VTE during the time they were on front line chemotherapy (12.5%). Nine patients (7%) had a pulmonary embolus (PE) and 8 (6.3%) had a deep vein thrombus (DVT). The average BMI in the group that developed VTE was 28 and in the group without VTE was 26.5 (p = 0.23). Three out of 16 (23%) patients who developed VTE had undergone a suboptimal cytoreduction compared to 12/112 (11%) in the group with no VTE (p = 0.4). Six of the 16 (37%) patients who developed VTE during chemotherapy underwent a bowel resection and/or splenectomy during their cytoreductive surgery compared to 18 of 112 (16%) patients who did not develop VTE (p=0.079). Eight of the patients in the VTE group had indwelling venous catheters during chemotherapy (50%) compared to 39 (35%) in the group with no VTE (p = 0.27). In the group that developed VTE, there was a trend towards increased pre-operative CA-125, higher rates of bowel resection and/or splenectomy during surgery, decreased use of aspirin, and inferior survival. On multivariate analysis, patients who developed VTE had significantly longer post-operative hospital stays (7 vs 5 days [p = 0.009]) and lower rates of complete response (p = 0.01). Conclusions: A 12.5% risk of VTE merits consideration of prophylaxis during chemotherapy in this cohort. A randomized, controlled trial is needed to clarify whether the benefits of long term prophylaxis outweigh the risks and costs of such therapy.

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Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis

Thrombosis and Haemostasis ◽

10.1160/th08-01-0052 ◽

2009 ◽

Vol 101 (03) ◽

pp. 541-546 ◽

Cited By ~ 13

Author(s):

Andreas Scorilas ◽

Sonia Markakis ◽

Diane Kowalski ◽

Robert L. Camp ◽

Eleftherios P. Diamandis ◽

...

Keyword(s):

Ovarian Cancer ◽

Survival Analysis ◽

Protein Expression ◽

Prognostic Significance ◽

Advanced Ovarian Cancer ◽

Progression Free Survival ◽

Protein Analysis ◽

Free Survival ◽

Response To Chemotherapy

SummaryKallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered to be important prognostic biomarkers in cancer. In this study we sought to determine the prognostic value of kallikrein-related peptidase 8 (KLK8,hK8,KLK-8) in ovarian cancer using a novel method of compartmentalised in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For the evaluation of kallikrein-related peptidase 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred twenty-six of 150 cases had sufficient tissue for AQUA analysis. There were significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade (p=0.0011), residual disease (p=0.0063) and clinical response to chemotherapy(p=0.0346). In univariate survival analysis there was a significant correlation between KLK8 tumour mask expression and five years progression-free survival, meanwhile it was not associated with five-year overall survival (p =0.0694). Specifically, low KLK8 expression correlated with better outcome (top vs. bottom quartile, p=0.0319). In multivariate survival analysis, adjusting for well-characterised prognostic variables, tumour KLK8 expression level retained its prognostic significance for progression-free survival (95%CI: 0.341–1.027, p=0.045). The possibility that KLK8 may be a suitable candidate as a diagnostic and prognostic marker warrants further investigation.

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Fibronectin and Periostin as Prognostic Markers in Ovarian Cancer

Cells ◽

10.3390/cells9010149 ◽

2020 ◽

Vol 9 (1) ◽

pp. 149 ◽

Cited By ~ 4

Author(s):

Katarzyna Aleksandra Kujawa ◽

Ewa Zembala-Nożyńska ◽

Alexander Jorge Cortez ◽

Tomasz Kujawa ◽

Jolanta Kupryjańczyk ◽

...

Keyword(s):

Ovarian Cancer ◽

Prognostic Factor ◽

Prognostic Markers ◽

Cox Regression ◽

Prognostic Significance ◽

Advanced Ovarian Cancer ◽

Independent Prognostic Factor ◽

Benign Tumors ◽

Molecular Features ◽

Kaplan Meier

Previously, based on a DNA microarray experiment, we identified a 96-gene prognostic signature associated with the shorter survival of ovarian cancer patients. We hypothesized that some differentially expressed protein-coding genes from this signature could potentially serve as prognostic markers. The present study was aimed to validate two proteins, namely fibronectin (FN1) and periostin (POSTN), in the independent set of ovarian cancer samples. Both proteins are mainly known as extracellular matrix proteins with many important functions in physiology. However, there are also indications that they are implicated in cancer, including ovarian cancer. The expression of these proteins was immunohistochemically analyzed in 108 surgical samples of advanced ovarian cancer (majority: high-grade serous) and additionally on tissue arrays representing different stages of the progression of ovarian and fallopian tube epithelial tumors, from normal epithelia, through benign tumors, to adenocarcinomas of different stages. The correlation with clinical, pathological, and molecular features was evaluated. Kaplan–Meier survival analysis and Cox-proportional hazards models were used to estimate the correlation of the expression levels these proteins with survival. We observed that the higher expression of fibronectin in the tumor stroma was highly associated with shorter overall survival (OS) (Kaplan–Meier analysis, log-rank test p = 0.003). Periostin was also associated with shorter OS (p = 0.04). When we analyzed the combined score, calculated by adding together individual scores for stromal fibronectin and periostin expression, Cox regression demonstrated that this joint FN1&POSTN score was an independent prognostic factor for OS (HR = 2.16; 95% CI: 1.02–4.60; p = 0.044). The expression of fibronectin and periostin was also associated with the source of ovarian tumor sample: metastases showed higher expression of these proteins than primary tumor samples (χ2 test, p = 0.024 and p = 0.032). Elevated expression of fibronectin and periostin was also more common in fallopian cancers than in ovarian cancers. Our results support some previous observations that fibronectin and periostin have a prognostic significance in ovarian cancer. In addition, we propose the joint FN1&POSTN score as an independent prognostic factor for OS. Based on our results, it may also be speculated that these proteins are related to tumor progression and/or may indicate fallopian–epithelial origin of the tumor.

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