Prognostic role of E-cadherin in patients with advanced serous ovarian cancer.

Dec 2012

Bačić B, Haller H, Mrklić I, Košta V, Carić A, Tomić S.

Source

Department of Obstetrics and Gynaecology, Split University Hospital Centre and School of Medicine, Spinčićeva 1, 21000, Split, Croatia, boris.bacic@st.t-com.hr.

Abstract

PURPOSE:

To analyse correlation between expression of E-cadherin and clinical and pathological features and overall survival in advanced-stage serous ovarian carcinoma.

METHODS:

The expression of E-cadherin was analysed immunohistochemically in formalin-fixed, paraffin-embedded samples from 54 patients with advanced-stage serous ovarian cancer and related to clinicopathological characteristics and patients survival. The clinicopathological characteristics included the stage according to the International Federation of Gynecology and Obstetrics (FIGO), tumour differentiation, number of mitoses per 10 high-power fields (HPF), residual tumour size, and vascular invasion. Only patients with serous ovarian cancer FIGO stages III-IV were included. Overall survival (OS) was defined as time from surgery to the last follow-up date on 01.10.2010. OS was evaluated using Kaplan-Meier method, and log-rank test was used to asses the differences between the positive and E-cadherin negative group. Multivariate analysis was completed using the Cox proportional hazard regression model.

RESULTS:

E-cadherin immunoreactivity was not associated with FIGO stage, tumour grade, number of mitotic figures per 10 HPF, residual tumour volume or vascular invasion. Negative E-cadherin expression significantly predicted shorter OS (p < 0.001). The multivariate analyses showed that negative E-cadherin (p < 0.001), FIGO stage (p = 0.012) and residual tumour size >1 cm after the initial cytoreductive surgery (p < 0.001) were predictors of shorter OS.

CONCLUSION:

Negative E-cadherin expression like presence of residual tumour after primary cytoreductive surgery and higher FIGO stage seem to predict unfavourable clinical outcome in patients with advanced-stage serous ovarian cancer. Negative expression of E-cadherin was shown to be a significant independent predictor of poorer OS. E-cadherin as marker has prognostic value.

Springerlink

The molecular biology of epithelial ovarian cancer.

Dec 2012

Leary A, Pautier P, Tazi Y, Morice P, Duvillard P, Gouy S, Uzan C, Gauthier H, Balleyguier C, Lhommé C.

Source

Institut Gustave-Roussy, département de médecine, comité pluridisciplinaire de gynécologie, 114, rue Édouard-Vaillant, 94800 Villejuif, France.

Abstract

Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.

PubMed

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

Dec 2012

Cândido EB, Silva LM, Carvalho AT, Lamaita RM, Filho RM, Cota BD, Silva-Filho AL.

Source

1Department of Obstetrics and Gynecology, Federal University of Minas Gerais, Belo Horizonte, Brazil.

Abstract

Innate and adaptive immune cells secrete different cytokines, which participate through distinct mechanisms in cell-mediated immunity and humoral immune responses. The aim of this study was to evaluate the immune response through analysis of type 1 (Th1), Th2, and Th17 cells in patients with epithelial ovarian cancer (EOC). Our study included 44 patients with EOC (study group) and 32 gynecological patients with no ovarian disease (control group). Fragments of ovarian tissue and blood samples were collected in both groups and aliquots of intracystic fluid and peritoneal fluid were recovered from the EOC patient group. Interleukin (IL)-2/IL-4/IL-6/IL-10/IL-17/tumor necrosis factor (TNF)-α/interferon (IFN)-γ levels were measured by cytometric bead array. Statistical analysis included chi-squared, Student t, Mann-Whitney, Kruskal-Wallis tests, and Cox regression model. Patients with EOC were associated with higher levels of TNF-α/IL-4/IL-6/IL-10 compared to the control group. Both IL-10 and TNF-α concentrations were higher in patients with stage III/IV EOC and also associated with higher levels of cancer antigen 125. Higher Th1-mediated immune response was observed when the cytoreduction was considered optimal. 

However, patients with EOC with unsatisfactory cytoreductive surgery and undifferentiated tumors were associated with higher concentrations of Th2 cytokines in the 4 sites studied. Higher IL-6/IL-10 and lower IFN-γ concentrations were also associated with a lower overall survival rate in patients with EOC. The EOC group presented a predominantly Th2 response and an immunosuppressant standard and had association between IL-6/IL-10/IFN-γ and prognosis.

PubMed

New insights into ovarian cancer pathology.

Sept 2012

Prat J.

Source

Department of Pathology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.

Abstract

Malignant epithelial tumors (carcinomas) are the most common ovarian cancers and also the most lethal gynecological malignancies. Based on histopathology and molecular genetic alterations, ovarian carcinomas are divided into five main types [high-grade serous (70%), endometrioid (10%), clear-cell (10%), mucinous (3%), and low-grade serous carcinomas (<5%)] that account for over 95% of cases. These types are essentially distinct diseases, as indicated by differences in epidemiological and genetic risk factors, precursor lesions, patterns of spread, and molecular events during oncogenesis, response to chemotherapy, and prognosis.

For a successful specific treatment, reproducible histopathological diagnosis of the tumor cell type is critical. The five tumor types are morphologically diverse and resemble carcinomas of the uterus. Actually, recent investigations have demonstrated that a substantial number of cancers, traditionally thought to be primary ovarian tumors (particularly serous, endometrioid, and clear-cell carcinomas), originate in the fallopian tube and the endometrium and involve the ovary secondarily. This presentation summarizes recent advances in the molecular pathology which have greatly improved our understanding of the biology of ovarian carcinoma and are also relevant to patient management.

PubMed

Influence of a family history of breast and/or ovarian cancer on breast cancer outcomes.

Sept 2011

Cao AY, He M, DI GH, Wu J, Lu JS, Liu GY, Shen ZZ, Shao ZM.

Source

Breast Cancer Institute, Cancer Hospital/Cancer Institute, Department of Oncology, Shanghai Medical College, Institutes of Biomedical Science, Fudan University, Shanghai, P.R. China.

Abstract

Various published studies have been inconclusive in attempting to relate a family history of breast and/or ovarian cancer(BOC) to the survival of breast cancer patients. The aim of the study was to investigate the association of a family history of BOC with tumor characteristics, treatment response and the difference between the prognosis of familial breast cancer (FBC) patients and sporadic breast cancer (SBC) patients. Data on 348 operable FBC patients and 345 SBC patients were retrospectively analyzed. The overall survival (OS) and recurrence/metastasis-free survival (RFS) were compared for both groups. FBC cases were diagnosed at a relatively younger age (51.1±10.4 vs. 53.7±11.0 years, P=0.054) and presented a lower T stage (P=0.000) than the SBC cases. Patients with a family history of BOC had a significantly greater risk of recurrence/metastasis (P= 0.04) and a non-significantly increased risk of death (P=0.06) compared to the SBC patients. In a multivariate analysis, family history of BOC was an independent predictive factor for both recurrence/metastasis rate (P=0.01, HR=0.012, 95% CI 0.02-0.57) and mortality (P=0.044, HR=0.43, 95% CI 0.19-0.98) in the hormone receptor-positive population. Our results found that women diagnosed with FBC had an early onset of disease in the population studied, and the poor outcome of patients with a family history of BOC associated with survival was restricted to the hormone receptor-positive population.

PubMed