Cellular Expression of Cyclooxygenase, Aromatase, Adipokines, Inflammation and Cell Proliferation Markers in Breast Cancer Specimen

Abstract

Current evidences suggest that expression of Ki67, cyclooxygenase (COX), aromatase, adipokines, prostaglandins, free radicals, β-catenin and α-SMA might be involved in breast cancer pathogenesis. The main objective of this study was to compare expression/localization of these potential compounds in breast cancer tissues with tissues collected adjacent to the tumor using immunohistochemistry and correlated with clinical pathology. The breast cancer specimens were collected from 30 women aged between 49 and 89 years who underwent breast surgery following cancer diagnosis. Expression levels of molecules by different stainings were graded as a score on a scale based upon staining intensity and proportion of positive cells/area or individually. AdipoR1, adiponectin, Ob-R, leptin, COX-1, COX-2, aromatase, PGF2α, F2-isoprostanes and α-SMA were localised on higher levels in the breast tissues adjacent to the tumor compared to tumor specimens when considering either score or staining area whereas COX-2 and AdipoR2 were found to be higher considering staining intensity and Ki67 on score level in the tumor tissue. There was no significant difference observed on β-catenin either on score nor on staining area and intensity between tissues adjacent to the tumor and tumor tissues. A positive correlation was found between COX-1 and COX-2 in the tumor tissues. In conclusion, these suggest that Ki67, COXs, aromatase, prostaglandin, free radicals, adipokines, β-catenin and α-SMA are involved in breast cancer. These further focus the need of examination of tissues adjacent to tumor, tumor itself and compare them with normal or benign breast tissues for a better understanding of breast cancer pathology and future evaluation of therapeutic benefit.

Fig 1. β-Catenin and Ki67 immunostaining in adjacent breast tissue to tumor or breast tumor tissue.

Adjacent breast tissue to tumor or breast tumor tissue labeled by indirect immunofluorescence for A/ β-catenin and B/ Ki67 (green) with DAPI as nuclear counterstain (blue).

Fig 2. Adiponectin and Adiponectin receptors immunostaining in adjacent breast tissue to tumor or breast tumor tissue.

Adjacent breast tissue to tumor or breast tumor tissue labeled by indirect immunofluorescence for A/ Adiponectin, and B/ Adiponectin receptor 1 and C/ Adiponectin receptor 2 (red) with DAPI as nuclear counterstain (blue).

Fig 3. Leptin and Leptin receptor immunostaining in adjacent breast tissue to tumor or breast tumor tissue.

Adjacent breast tissue to tumor or breast tumor tissue labeled by indirect immunofluorescence for A/ Leptin and B/ Leptin receptor Ob-R (red) with DAPI as nuclear counterstain (blue).

Fig 4. COX-1 and COX-2 immunostaining in adjacent breast tissue to tumor or breast tumor tissue.

Adjacent breast tissue to tumor or breast tumor tissue labeled by indirect immunofluorescence for A/ COX-1 (red) and B/ COX-2 (green) with DAPI as nuclear counterstain (blue).

Fig 5. F₂-isoprostane and PGF_2α immunostaning in adjacent breast tissue to tumor or breast tumor tissue.

Adjacent breast tissue to tumor or breast tumor tissue labeled by indirect immunofluorescence for A/ F₂-isoprostane and B/ PGF_2α (green) with DAPI as nuclear counterstain (blue).

Fig 6. Aromatase and α-SMA immunostaning in adjacent breast tissue to tumor or breast tumor tissue.

Adjacent breast tissue to tumor or breast tumor tissue labeled by indirect immunofluorescence for A/ Aromatase (red) and B/ α-SMA (green) with DAPI as nuclear counterstain (blue).