Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer

Abstract

Molecular profiling is a powerful approach to identify potential clinical markers for diagnosis and prognosis as well as providing a better understanding of the biology of epithelial ovarian cancer. On the basis of the analysis of HuFL expression data, we have previously identified genes that distinguish low malignant potential and invasive serous epithelial ovarian tumors. In this study, we used immunohistochemistry to monitor a subset of differently expressed candidates (Ahr, Paep, Madh3, Ran, Met, Mek1, Ccne1, Ccd20, Cks1 and Cas). A tissue array composed of 244 serous tumors of different grades (0–3) and stages (I–IV) was used in this analysis. All markers assayed presented differential protein expression between serous tumors of low and high grade. Significant differences in Ccne1 and Ran expression were observed in a comparison of low malignant potential and grade 1 tumor samples (p < 0.01). In addition, irrespective of the grade, Ccne1, Ran, Cdc20 and Cks1 showed significant differences of expression in association with the clinical stage of disease. While high level of Ccne1 have previously been associated with poor outcomes, here we found that high level of either Ran or Cdc20 appear to be more tightly associated with a poor prognosis (p < 0.001, 0.03, respectively). The application of these biomarkers in both the initial diagnosis and prognostic attributes of patients with epithelial ovarian tumors should prove to be useful in patient management. © 2006 Wiley‐Liss, Inc.

Tumor Cell Dependence on Ran-GTP–Directed Mitosis

“…This is consistent with a role of Ran and its effector molecules in chromosome positioning (38), loading of spindle checkpoint proteins (39), and organization of kinetochore fibers (40), all mechanisms that are crucial for proper chromosome segregation. Supporting this model, the Ran targets TPX2 and Aurora A were recently identified in a chromosomal instability gene signature associated with poor outcome in various types of cancer (41), and gene profiling data in ovarian cancer (42) and experimental breast cancer (43) have consistently linked increased Ran levels to disease progression.…”

Transforming Growth Factor-β1, Transforming Growth Factor-β2, and Transforming Growth Factor-β3 Enhance Ovarian Cancer Metastatic Potential by Inducing a Smad3-Dependent Epithelial-to-Mesenchymal Transition

“…This study reported that Smad3 expression could be used to differentiate between grade 0 and grade 1 or grade 0 and grade 2 serous tumors. Furthermore, high Smad3 expression correlated with patients having survival times of <18 months (29). This particular study scored only two tissue core punches, whereas we scored three tissue core punches for each patient.…”

An apoptotic molecular network identified by microarray: On the TRAIL to new insights in epithelial ovarian cancer

“…19 Tissue sections were heated to 608C for 30 minutes, deparaffinized in toluene, and rehydrated in an ethanol gradient. After 3% H 2 O 2 treatment, slides were submerged in boiling citrate buffer (0.01 M citric acid adjusted to pH 6.0) for 15 minutes, blocked with a protein blocking serum-free reagent (DakoCytomation Inc., Mississauga, Ontario, Canada), and incubated with the antibody for 60 minutes at room temperature.…”