Expression of CDCP1 and ADAM12 in the ovarian cancer microenvironment.

PURPOSE: The tumor microenvironment in ovarian cancer (OC) seems to play an important role, and besides tumor cells, biomarkers can derive from endothelial cells. We investigated CDCP1 and ADAM12 expression in relation with other clinical and pathological characteristics in OC patients. METHODS: We retrospectively evaluated patient files between 2006-2011. A histochemical score was developed to evaluate tumor staining, the microvessel density (MVD), and stromal expression patterns for both ADAM12 and CDCP1. A CD34 antibody was used to assess tumor MVD. RESULTS: 102 patients were selected and 83% had FIGO stage III/IV. A high CDCP1 tumor score correlated significantly with a shorter overall survival (OS) (p<0.01). Cases with positive CDCP1 had an elevated CD34 MVD (p<0.01). An absent/low ADAM12 tumor score correlated with significantly improved OS (p<0.01). Mean CD34 MVD was higher in cases with positive ADAM12 MVD (p=0.012). CONCLUSIONS: Our results indicate that both tumor markers are negative prognostic factors for overall survival and additional studies are required to validate their future potential.

Expression of Nestin and CD133 in serous ovarian carcinoma.

Pupose: Nestin and CD133 are regarded as putative markers of cancer stem cells (CSCs) and related to poor prognosis in various cancer sites. Since few studies have focused on their role in ovarian cancer, we aimed to investigate their predictive value and association with neoangiogenesis. METHODS: Immunohistochemical analysis for nestin and CD133 was performed on 85 serous ovarian carcinoma tumor samples using tissue microarray technique. Nestin immunoreactivity was detected in both tumor and endothelial cells, whilst CD133 was only identified in tumor cells. CD34 endothelial expression was used to assess intratumor microvessel density (MVD). RESULTS: Of the tissue samples 49.4% were nestin-positive and 24.7% were positive for CD133. In both univariate and multivariate analysis nestin or CD133 expressions in tumor cells were not significantly associated with clinicopathological parameters (age, serum CA125, peritoneal carcinomatosis, malignant ascites, tumor grade). However, in multivariate analysis nestin expression in tumor cells proved to be an independent prognostic factor, associated with poorer survival and time to progression (p=0.025 and p=0.05, respectively). This has not been achieved for CD133. Furthermore, a significant concordance between nestin endothelial expression (nestin-determined MVD) and CD34-determined MVD was achieved. CONCLUSION: In addition to the well-known clinicopathological characteristics, tumor expression of nestin might be a valuable prognostic factor for survival in patients with advanced ovarian cancer. With regard to its endothelial expression, nestin might be as reliable as CD34 for quantifying tumor angiogenesis. Further investigation is justified in order to better clarify the role of these biomarkers.

The role of CDCP1 (CUB domain-containing protein 1) and ADAM12 (a disintegrin and metalloproteinase 12) in ovarian cancer.

Ovarian cancer (OC) is the second most common gynecological cancer and the deadliest in industrialized countries, with poor outcomes that indicate an urgent need to provide a greater insight into the molecular mechanisms underlying OC. Insights into the complex tumor microenviroment show that besides tumor islets, OC biomarkers can derive from newly formed blood vessels that have endothelial cells with a different molecular signature in comparison with their normal counterparts. In this view, recent research has been able to highlight promising candidates such as CDCP1 and ADAM12. Our present review summarises their implications in cancer progression with a focus on OC.

Current insights into the association of Nestin with tumor angiogenesis.

Tumor angiogenesis is regarded as a hallmark of cancer and provides an important target for therapy. Nestin is an intermediate filament protein (IF) originally recognized as a neural stem cell marker. Development and progression of cancer requires sustained angiogenesis, dependent on the proliferation and migration of endothelial cells which seem to be better portrayed by nestin expression in various malignancies such as central nervous system, gastro-intestinal cancers, malignant melanoma, lung, prostate or breast cancer. The purpose of the present review was to emphasize the insights into nestin expression in relation to tumor angiogenesis in different types of cancer. Current evidence suggests that nestin positivity in tumor cells reflects stem-like properties of those cells. Whether or not expressed in both tumor and endothelial cells, nestin overexpression might reflect the extent of angiogenesis and function as a molecular anti-angiogenic target for cancer.

Clinical outcomes and cost-effectiveness of primary treatment of ovarian cancer in North-Western Romania.

PURPOSE: Ovarian cancer has the poorest survival rate among gynaecological malignancies. Besides the comparison of different therapeutic strategies aimed to improve outcomes, studies have also begun to focus on aspects of cost-effectiveness of these strategies. In this context, we proposed to evaluate the survival impact, costs and cost-effectiveness of two primary treatment options, primary debulking surgery (PDS) versus neoadjuvant chemotherapy (NACT), in patients with advanced ovarian cancer treated in a tertiary cancer center of the North-Western Romania. METHODS: The study included patients with stages IIIC and IV ovarian cancer treated at the "Prof. Dr. Ion Chiricuta" Institute of Oncology, Cluj-Napoca, between 2008-2011, by either PDS or NACT. Survival was the measure of the effectiveness of the two treatments. A cost-effectiveness analysis was carried out by estimating the incremental cost-effectiveness ratio (ICER) and the average cost-effectiveness ratio (ACER). RESULTS: There was no significant difference in overall survival between the two treatment groups. The median costs for the NACT subgroup were 3580.41 € compared to 2990.19 € for the PDS subgroup, with an incremental cost of 590.22 €. The effectiveness measured in years of survival was 3.34 years for NACT and 3.57 years for PDS. The corresponding median ICER was -2566.17 €/year of survival. ACER was higher for NACT compared to PDS (1071.98 vs. 837.59 €/year of survival). CONCLUSIONS: Despite the higher costs, NACT did not prove to be a more effective therapeutic strategy in terms of survival of patients with stage IIIC/IV ovarian cancer. Altogether, our results state that NACT might be less cost-effective than PDS.

The role of CD146 in serous ovarian carcinoma.

PURPOSE: The heterogeneous phenotype of epithelial ovarian cancer (EOC) explains the unpredictable behaviour in terms of response to therapy, time to progression and survival. In this context, CD146, a cell adhesion molecule, has been focused on as a marker of poor prognosis in various solid cancers, being also capable to modulate the activity of endothelial cells. Therefore, we proposed to investigate its role in serous ovarian carcinoma. METHODS: The study included 101 patients diagnosed with EOC and treated within "Ion Chiricuta" Oncology Institute by optimal surgical debulking followed by platinum-based chemotherapy. Clinico-pathological characteristics were collected from patient files. CD146 expression was assessed by immunohistochemistry in serous ovarian carcinoma primary tumours, taking into account both staining intensity and the percentage of positive tumor cells. Expression of CD146 in endothelial cells of tumour microvessels was also evaluated. CD34 immunostaining was used for intratumoral microvessel density estimation. RESULTS: CD146 positivity in tumor cells was objectified in 49.5% of samples and 37.1% presented a high CD146 endothelial expression. Our analysis showed that CD146 was as reliable as CD34 for microvascular density estimation. The distribution of cases according to CD146 tumor expression was similar regardless of age, initial serum CA125 level, FIGO stage, presence/absence of malignant ascites. Multivariate analysis confirmed that expression of CD146 in tumor cells was a negative prognostic factor for overall survival, significantly asociated with a higher risk of chemotherapy resistance. CONCLUSIONS: Although CD146 immunoreactivity in tumor cells did not correlate with the routinely used clinico-pathological parameters, expression of CD146 in tumor cells was an independent pronostic factor for survival in serous ovarian carcinomas. Moreover, CD146 might be regarded as a novel biomarker of tumor neovasculature.