Background and Aim: The biological role of never growth factor and its p75 receptor in prostate cancer is still controversial. The aim of this work was to evaluate the localization of p75 in normal and neoplastic human prostate as prognostic marker. Patients and Methods: Human samples of normal and prostate cancer were analyzed at light and ultrastructural levels (transmission electron microscopy, TEM). At the light microscopical level, p75 immunoreactivity (IR) in normal human prostate was restricted to the basal cells of the acini, at epithelial-stromal junction. This result was confirmed by TEM. Normal prostatic stromal cells were p75 negative, except for nerves and blood vessels. Prostatic intraepithelial neoplasia showed a relevant proliferation of the epithelial compartment, inclusive of the basal cells that remained p75 IR. However, samples of adenocarcinoma, medium to high grade neoplasia, showed different patterns of p75 localization. In fact, while basal cells of the epithelial compartment became progressively p75 negative, a novel strong p75 IR was detected in the stromal compartment, adjacent to the neoplastic acini. Ultrastructural analysis showed that the stromal p75 IR was localized on plasma membrane of smooth muscle cells. Other stromal cells were p75 negative. The amount of p75 IR in the stroma seems to be positively correlated to Gleason score. Results: Our study shows a novel morphological localization of p75 in the stroma of prostate tumour. The positive correlation of this stromal localization with the tumour malignancy suggests a progressive dedifferentiation of the smooth muscle cells that are normally p75 negative. This dedifferentiation of neoplastic smooth muscle cells around the neoplastic acini could be relevant for metastatic invasion of the stroma. Conclusion: Our findings of p75 in the stromal compartment of prostate cancer shows that it could be a novel marker for a better definition of the prostatic cancer malignancy and prognosis.
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