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Abstract
BackgroundThe current study evaluated the metalloproteinases MMP-2 and MMP-9 expression in epithelial cells and the surrounding stroma in ovarian tumors and the association of MMPs with the histological subtypes, the clinical stage and the presence of steroid hormone receptors. Tumor samples were obtained from 88 patients undergoing surgical cytoreduction of primary ovarian tumors in Instituto Nacional de Cancerología, from México City. The formalin fixed and paraffin embedded samples were processed in order to demonstrate the presence of androgen receptor,estrogen receptor alpha, progesterone receptor, MMP-2,MMP-9 and collagen IV by immunohistochemistry and/or immunofluorescence.ResultsMMP-2 and MMP-9 were differentially expressed in the epithelium and the stroma of ovarian tumors associated to histological subtype, clinical stage and sexual steroid hormone receptor expression. Based on Cox proportional hazard regression model we demonstrated that MMP-2 located in the epithelium and the stroma are independent prognostic biomarkers for overall survival in epithelial ovarian tumors. Kaplan Meir analysis of the combination of AR (+) with MMP-2 (+) in epithelium and AR (+) with MMP-2 (−) in stroma displayed a significant reduction of survival.ConclusionsThe presence of MMP-2 in the stroma of the tumor was a protective factor while the presence of MMP-2 in the epithelium indicated an adverse prognosis. The presence of AR associated with MMP-2 in the tumor cells was a risk factor for overall survival in epithelial ovarian cancer.
Highlights
Ovarian cancer is the third in frequency and the first in lethality out of all gynecological malignancies and every year about 185.000 women die of this causeworldwide [1]
Histological subtypes The following proportions of histological subtypes were observed in epithelial ovarian tumors: serous borderline tumor 20/88, high grade serous carcinoma 21/88, endometrioid carcinoma 21/88, mucinous carcinoma 11/88, and low grade serous carcinoma 9/88
Ovarian cancer cells express Matrix metalloproteinase (MMP)-2 and MMP-9 Differential frequency in the expression of MMP-2 and MMP-9 was observed in epithelial and stromal compartments considering the total of tumor samples: 85 and 56% in epithelium and 65 and 16% in stroma, respectively
Summary
Ovarian cancer is the third in frequency and the first in lethality out of all gynecological malignancies and every year about 185.000 women die of this causeworldwide [1]. MMP-2 and MMP-9, known as “gelatinases”, destroy the barriers enclosing a tumor, including collagen IV of the basement membrane and the extracellular matrix, allowing invasion into the surrounding tissue [6, 7]. Previous studies have described the expression of MMPs in epithelial ovarian cancer and evaluated the presence of MMP-2 and MMP-9 in the tumor as potential biomarkers of aggressiveness of the malignancy, registering the disease-free period and the overall survival of patients [13,14,15,16,17,18]. The current study evaluated the metalloproteinases MMP-2 and MMP-9 expression in epithelial cells and the surrounding stroma in ovarian tumors and the association of MMPs with the histological subtypes, the clinical stage and the presence of steroid hormone receptors. The formalin fixed and paraffin embedded samples were processed in order to demonstrate the presence of androgen receptor,estrogen receptor alpha, progesterone receptor, MMP-2,MMP-9 and collagen IV by immunohistochemistry and/or immunofluorescence
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