Kinetic profiles of intraepithelial and invasive prostatic neoplasias: thekey role of down-regulated apoptosis in tumor progression

The cell kinetic of prostatic intraepithelial neoplasia (PIN) is poorly und erstood. Herein we report the kinetic pattern of PIN, both not associated ( primary) and associated (secondary) with coexistent invasive carcinoma (PCa ). Surgical specimens collected in 20 cases of primary PIN, 20 of secondary PIN and 20 of PCa were studied by MIB-1 immunostaining, in situ end-labeli ng (ISEL) and DNA histogram analysis, and the cell density in each case was estimated using the formula N=(n pi/4)(2). Fifty high-power fields (HPF), or the complete lesion if smaller, were screened in each lesion, and both m ean and standard deviation were recorded. Statistical differences were stud ied by means of Fisher's exact test. ISEL indices were significantly (P<0.0 001) lower in PCa (0.1+/-0.3) than in primary PIN (0.5+/-0.3), while the MI B-I indices were similar in both conditions (P=0.56). Statistically signifi cant differences were also detected for both MIB-I and ISEL indices when se condary PIN (MIB-1 1.9+/-0.7, ISEL 3.7+/-3.3) was compared with primary PIN (MIB-I 2.5+/-2.1, ISEL 0.5+/-0.3) and PCa (P<0.0001). In terms of cellular ity, primary PIN (26.3+/-7.1) revealed scores significantly lower (P<0.0001 ) than those recorded in PCa (39.0+/-8.8) and secondary PIN (32.9+/-14.3). In conclusion, early prostatic tumor is mainly defined by down-regulated ap optosis rather than by increased proliferation. Secondary PIN displays uniq ue kinetic features suggesting an evolved stage of primary PIN.