Association of myeloperoxidase with ovarian cancer

Abstract

Myeloperoxidase (MPO) is an oxidant generating enzyme normally restricted to myeloid cells, however aberrant MPO expression has been found to occur in non-myeloid cells in some disease states. The functional -463GA promoter polymorphism alters MPO expression levels. The -463G is within an SP1 binding site and is associated with higher gene expression. The G allele is most frequent with ~62% of European populations being GG homozygotes. The GA polymorphism has been associated with risk or survival in a variety of cancers including lung and breast cancer. In this study we determined the frequency of the -463G/A polymorphism in 230 ovarian cancer patients, 75 patients with borderline ovarian tumors, and 299 healthy controls. The GG genotype was found to be overrepresented in patients with early stage ovarian cancer (83.3% GG, p = 0.008) as compared to healthy controls (62% GG), suggesting that MPO oxidants may increase risk. Immunohistochemical analysis revealed MPO expression in a subset of columnar ovarian epithelial carcinoma cells in early stage carcinomas.

Figure 1

MPO expression in epithelial ovarian cancer cells. A. Digital confocal image (Delta Vision microscope) of stage 1 ovarian endometriod cancer shows MPO (Alexa Fluor 488, green) immunostaining in columnar ovarian epithelial cancer cells, and nearby CD68 positive (Alexa Fluor 594, red) monocyte-macrophages lacking MPO co-staining. B. Digital confocal image of another region of the same tumor showing MPO (Alexa Fluor 488, green) positive epithelial cancer cells in the absence of nearby CD68 positive macrophages (Alexa Fluor 594, red). C. Digital confocal image from the same tumor showing colocalization (yellow) of MPO (Alexa Fluor 488, green) and CD68 (red) in macrophages invading an epithelial structure. D. Control image of a nearby section of the same ovarian cancer section seen in panel A showing lack of fluorescent staining with the Alexa Fluor 488 anti-rabbit IgG in the absence of the primary antibody. E. Control image of a nearby section stained with an irrelevant rabbit IgG antibody and the Alexa Fluor 488 anti-rabbit IgG. F. Control image of a section near that seen in panel C stained with an irrelevant mouse IgG control antibody and Alexa Fluor 594 anti-mouse IgG. G. MPO immunoperoxidase staining in a papillary region of a borderline tumor. H. Boxed area in panel D is shown at higher magnification showing MPO immunostaining in a complex cellular structure. I. High levels of MPO immunostaining (red arrow) in a stage 3 serous tumor in both tumor cells and infiltrating neutrophils and monocyte-macrophages.