Purpose: Ovarian/primary peritoneal serous carcinoma (OC/PPC) and diffuse peritoneal malignant mesothelioma (DMPM) are highly aggressive tumors that are closely related morphologically and histogenetically. It remains unclear whether both tumors are molecularly distinct neoplasms. The current study compared global gene expression patterns in OC/PPC and DMPM. Experimental Design: Ten OC/PPC and five DMPM effusions were analyzed for gene expression profiles using the Affymetrix U133 Plus 2 arrays and the dCHIP analysis program. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Results: Unsupervised hierarchical clustering using all 54,675 genes in the array classified the samples into two groups: DMPM specimens versus OC/PPC specimens. A total of 189 genes that were differentially expressed in these two groups were selected based on statistical significance. Genes overexpressed in DMPM (n = 68) included calretinin, vitronectin, claudin 15, a 4 laminin, hyaluronan synthase 1, cadherin 11, RAB7, v-maf, and the epidermal growth factor^containing fibulin-like extracellular matrix protein 1. Genes overexpressed in OC/PPC (n = 121) included insulin-like growth factor II (IGF-II); IGF-II binding protein 3; cyclin E1; folate receptors 1 and 3; RAB25; MUC4; endothelin-1; CD24; kallikreins 6, 7, and 8; claudins 3, 4, and 6; Notch3; and MMP-7. Quantitative real-time PCR validated the differential expression of 13 genes, and immunohistochemistry confirmed the differences for four gene products. Conclusions: Expression profiling separates OC/PPC from DMPM and identifies a number of genes that are differentially expressed in these tumors. The molecular signatures unique to OC/PPC and DMPM should provide a molecular basis to study both tumors and new potential markers for facilitating their differential diagnosis.Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive cancer that originates from the native mesothelial cells of the peritoneal cavity. DMPM is less common than its pleural counterpart (9:1 ratio), differs in its gender predilection (roughly similar incidence in women and men), and has a weaker etiologic link to asbestos exposure (1, 2). The prognosis of DMPM patients has been extremely poor in earlier series, with median survival of 10 to 12 months (2). However, recent studies have shown improved survival (26-92 months) when DMPM patients are treated aggressively with combined debulking and preheated i.p. chemotherapy consisting of cisplatin, doxorubicin, and paclitaxel as major agents (2 -4). Recently, a response rate of 25% was achieved following pemetrexed treatment (5). The majority of DMPM are of the epithelioid type (6).Ovarian cancer (OC) is the most lethal gynecologic malignancy in the Western world and the fourth most frequent cause of cancer-related death in women (7). As DMPM, OC and the closely related and morphologically indistinguishable primary peritoneal carcinoma (PPC) are thought to develop from the peritoneal mesot...

Objective The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers. Methods Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls. Results In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P= 0.015, McNemar's test). Conclusion Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer.

Abstract. Patients with the most common advanced human cancers such as lung, breast, uterus, and cancers of the digestive system almost always develop bone metastases, with painful and untreatable consequences. This study aimed to determine the prognostic implications of the neutrophil/lymphocyte (N/L) ratio in the peripheral blood of patients with malignant bone metastasis. Study participants were identified from a prospective cohort of cancer patients with bone metastasis. Data for the N/L ratios were obtained from clinical and pathological records and were analyzed together with other known prognostic factors in the multivariate and univariate analyses. The results showed the average N/L ratio of all 497 patients to be 4.25±2.44 (range 0.54-45.50 years). Multivariate analysis revealed that tumor type and a high N/L ratio were significantly associated with poor prognosis. For the high N/L ratio group, the estimated hazard ratio of death was 1.348 [95% confidence interval (CI), 1.062-1.712] compared with the low N/L ratio group. The average N/L ratio of the 225 patients in the surgery group was 2.79±2.46 (range 0.77-22.75 years). Multivariate analysis revealed that a preoperatively high N/L ratio (P=0.013; HR=2.945; 95% CI, 1.256-6.906) was significantly associated with poor prognosis after bone metastasis in the surgery group. In conclusion, the N/L ratio was confirmed to be an independent prognostic factor in patients with bone metastasis. Thus, the N/L ratio may serve as a clinically accessible and useful biomarker for patient survival.

No abstract

No abstract