Prostatic intraepithelial neoplasia (PIN) is the most likely precursor
of human prostate cancer. The prevalence and immunophenotype of PIN i
n dogs with spontaneous prostate cancer has not been previously descri
bed. To investigate the association between PIN and prostate cancer, w
e evaluated the prostates of dogs with spontaneous prostate carcinoma.
The prevalence of PIN was determined in formalin-fixed prostates from
29 dogs with spontaneous prostate cancer. Using immunoperoxidase tech
niques, we compared basal cell layer integrity (high molecular weight
keratin 34 beta-E12), proliferative index (MIB-1), and microvessel den
sity (Factor VIII-related antigen) in 14 prostates which contained ben
ign epithelium, PIN, and carcinoma. PIN was present in 19 of 29 (66%)
prostates from dogs with spontaneous prostate cancer. The basal cell l
ayer was intact in benign epithelium, disrupted in 72% of: acini with
PIN, and absent in carcinoma. The mean proliferative index was 17%, 25
%, and 40% for benign epithelium, PIN, and carcinoma, respectively, an
d these differences were significant. The mean microvessel density in
foci of PIN and carcinoma (32 and 39 vessels per mm(2), respectively)
was greater than in benign epithelium (23 vessels per mm(2)). High-gra
de PIN is common in the prostates of dogs with spontaneous carcinoma.
The basal cell layer is partially disrupted in PIN, whereas it is abse
nt in prostate cancer. The proliferative index and microvessel density
of PIN are intermediate between benign epithelium and cancer. These r
esults are similar to those reported for human PIN and prostate cancer
, and indicate that PIN is part of a morphologic continuum in the prog
ression of prostate cancer. To our knowledge, this is the first descri
ption of high-grade PIN spontaneously occurring in animals. The canine
prostate may serve as: a useful model for examining factors that modu
late PIN and prostate cancer progression. (C) 1997 Wiley-Liss, Inc.