Alterations of E-cadherin and MMP-2 in cancer prostate

ABSTRACT

E-cadherin plays a crucial role in epithelial cell-cell adhesion and maintenance of tissue architecture. Alterations in expression or function of this protein result in loss of intercellular adhesion, with possible consequent increased tumor progression, metastasis, and poor prognosis in different cancer types. Matrix metalloproteinases [MMPs] constitute a multi-gene family of proteolytic enzymes that are capable of degrading connective tissue and almost all extracellular matrix components. Overexpression of MMPs is usually associated with the acquisition of invasiveness by tumor cells, cancer progression, angiogenesis and metastasis. To examine the expression of E-cadherin and MMP-2 in male prostatic lesions using immunohistochemical staining. 30 cases of formalin-fixed, paraffin embedded tissues of male prostatic lesions were examined for the expression of E-cadherin and MMP-2 using immunohistochemistry utilizing rabbit antihuman polyclonal antibodies for E-cadherin and MMP-2. The tissue specimens comprise samples of 25 prostatic adenocarcinoma [PAC] and five benign prostatic hyperplasia [BPH]. H and E histological examination revealed that of the 25 studied malignant cases, six were combined grade CG 10; three were CG9; two were CG8; three were CG7; four were CG6; and seven were CG5, according to combined Gleason's grading system. Immunostaining showed altered expression [cytoplasmic] of E-cadherin in poorly and moderately differentiated foci of carcinoma [CG6-10]. Cell membrane expression of E-cadherin was seen in well differentiated foci as well as in BPH. However for immunostaining of MMP-2, very weak expression of it was seen in BPH as well as in normal glands adjacent to tumor cells. Mild to moderate staining intensity was observed in well differentiated PAC and moderate intensity was seen in moderately differentiated PAC. Overexpression of MMP-2 in the form of positive cytoplasmic aggregates was shown in poorly differentiated PAC. The results suggest the implication of the altered expression of E-cadherin and MMP-2 in increased aggressiveness of the tumor with its subsequent increased invasiveness and progression. Also show that increased expression of collagenase type IV [MMP-2] and decreased expression of E-cadherin are associated with increasing Gleason score and that the expression of MMP-2 and E-cadherin exhibited strongest association with advanced prostate cancer