IMMUNOHISTOCHEMICAL EVALUATION OF TYPE-IV COLLAGENASE (72-KD METALLOPROTEINASE) IN PROSTATIC INTRAEPITHELIAL NEOPLASIA

The aim of this study was to investigate the expression of type IV col lagenase (72-kd metalloproteinase, MMP-2) in prostatic intraepithelial neoplasia (PIN) in relation to normal prostate (NP) and prostatic ade nocarcinoma (PAc). Twenty formalin-fixed, paraffin-embedded prostatect omy specimens, in which NP, PIN and PAc were present, were immunohisto chemically examined. The NP ducts and acini not contiguous with PIN an d PAc showed slight MMP-2 immunostaining in the secretory cells, with some increase in intensity at the apical border, and moderate to stron g immunoreactivity of some basal cells. In NP adjacent to PIN and PAc, rare ducts and acini showed strongly stained cells either isolated or in small groups of two, located within the thickness of the epitheliu m, close to the basement membrane. In the majority of PIN ducts and ac ini, the stratified secretory cells showed moderate staining. Most of these ducts and acini also showed strongly stained cells, which were m ostly isolated, and either in contact with the basement membrane or sc attered among the secretory cells. Low and high grade PIN showed some difference in the frequency of dark cells, which were more numerous in the latter. A small group of neoplastic acini adjacent to high grade PIN (early invasive adenocarcinoma) was observed in one of the 20 case s. Intense immunostaining was present in the acini originating from th e PIN lesion. MMP-2 immunostaining of PAc was heterogeneous in intensi ty and location. Cribriform and solid/trabecular PAc showed weak cytop lasmic immunostaining; both moderately and intensely stained cells wer e seen in the cell layer adjacent to the stroma, intense immunostainin g was shown by small clusters of neoplastic cells or single neoplastic cells located in the stroma. In acinar PAc, weak cytoplasmic immunost aining for MMP-2 was seen throughout most areas of the tumours, wherea s moderately and intensely stained cells were observed less frequently than in cribriform and solid/trabecular adenocarcinoma. Intense immun ostaining of single or small clusters of neoplastic cells located in t he stroma was occasionally observed and, as with cribriform and solid/ trabecular PAc, mainly located towards the periphery of the tumour nod ules. Occasional ducts and acini with PIN and foci of PAc were either completely negative or very weakly stained. In conclusion, MMP-2 immun ostaining increases progressively from NP, through PIN, up to invasive PAc. These results directly support the hypothesis that increased exp ression of metalloproteinases is a marker of malignant conversion.