Figure 1.

Multistate prostate carcinogenesis determined by the progression of different qualitative states identifiable in the development of cancer from normal tissue. The time parameter (t ₀, t ₁,…, t _n−1, t _n) depends on a large number of variables interconnected in many ways in a nonlinear manner. This makes it extremely difficult to predict the exact time interval between two successive states. Although carcinogenesis is a continuum, its differentiation into successive states is based on differences in histological and clinical data. Proliferative inflammatory atrophy (PIA) is a frequently observed lesion in prostate biopsies and some investigators have postulated its involvement in prostate carcinogenesis. PIA shares genetic alterations with high-grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer. HGPIN is currently regarded as the precursor lesion on the basis of pathological, epidemiological, and cytogenetic evidence. HGPIN lesions can be subdivided into at least four different architectural patterns.