Ovarian Cancer Pathogenesis Correlated with Decreased Expression of Protein SLUG

Overview

Ovarian cancer is the fifth leading cause of cancer death among American women, in large part due to failure to diagnose the disease before it has spread to other organs. Recently, a change in the expression of regulatory molecules called microRNAs (miRNAs) in the fallopian tube epithelium has been recognized as an important early event in ovarian cancer growth. Two of these miRNAs, mir-335 and mir-92a, are thought to regulate the production of a zinc-finger transcription factor called SLUG, which coordinates cell differentiation and metastasis. The goal of this study was to analyze the expression of SLUG in ovarian cancer. The null hypothesis was that expression of SLUG would be the same between the two tissue types. This study used immunohistochemistry to analyze the presence of SLUG in murine xenografts made from the human ovarian cancer cell line OVCAR3. Sixteen OVCAR3 xenografts were compared to normal tissues from three non-tumor bearing mice. After being cut from paraffin blocks and attached to glass slides, the slides were dewaxed and placed into a pressure cooker for antigen retrieval. Slides were incubated with a blocking buffer before being incubated with rabbit anti-SLUG primary and anti-rabbit biotinylated secondary antibodies. Then the slides were incubated with an avidin/enzyme complex and exposed to the substrate DAB. The slides were counterstained with hematoxylin and coverslipped before they were examined by light microscopy. Histologic sections were evaluated by scoring the proportion of target cells staining for SLUG and the intensity of the stain. Both measures were score from 0 to 3 and then multiplied together to create an H-score for each section. Ovarian follicles were used as positive controls, while sections incubated without primary antibody were used as negative controls. Interobserver agreement was assessed by calculating a weighted Cohen’s Kappa statistic. The median H-scores between normal fallopian tube epithelia and ovarian cancers were compared using a Mann-Whitney U test. An alpha statistic less than 0.05 was considered statistically significant. The weighted Kappa statistic for the H-scores was 0.67 (95% CI 0.53 – 0.81), which falls within the “good” range of concordance. The null hypothesis was rejected, as the staining patterns for SLUG were markedly different between normal fallopian tube epithelium and ovarian cancer tumors. This suggests that SLUG expression may be an important biomarker for ovarian cancers and could play a role in ovarian cancer pathogenesis.

Competition history

• AJAS 2019 Category not listed

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