Waters D J, Bostwick D G
Cancer Biology Laboratory, Purdue University, West Lafayette, Indiana 47907, USA.
J Urol. 1997 Feb;157(2):713-6.
Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer. Although the dog is the only non-human species in which spontaneous prostate cancer occurs frequently, the prevalence of PIN in the canine prostate is unknown. A naturally occurring animal model of PIN has not been described.
To determine if high grade PIN occurs spontaneously in the canine prostate, we evaluated totally embedded prostates from 35 outbred dogs that had no clinical evidence of prostatic disease. Prostates from three groups of dogs were analyzed: (1) 11 sexually intact dogs 7-17 years old (elderly sexually intact); (2) 13 sexually intact dogs 1-4 years old (young sexually intact); and (3) 11 dogs 7-17 years old that had been castrated (elderly castrated). The prevalence of PIN was determined by systematic evaluation of hematoxylin/eosin and high molecular weight keratin 34 beta-E12 stained tissue sections from formalin-fixed, paraffin embedded prostates that had been serially sectioned at 4 mm intervals.
Canine high grade PIN showed cytologic features identical to the human counterpart, including cell crowding, loss of polarity, and nuclear and nucleolar enlargement. Foci of high grade PIN were present in the prostates of 6 of 11 (55%) elderly, sexually intact dogs but only 1 of 13 (8%) dogs less than 4 years old. Foci of high grade PIN were detected in 1 of 11 (9%) elderly castrated dogs. In elderly, sexually intact dogs with PIN, foci of high grade PIN were present in 13 of 83 (16%) tissue sections evaluated; one of these dogs had focal adenocarcinoma in addition to PIN.
These results indicate that high grade PIN is frequently present in the prostate of elderly, sexually intact dogs. The prevalence of canine PIN, like human PIN, is apparently influenced by age and testicular androgens. The canine prostate may serve as a useful model to determine the factors that regulate the apparent progression from benign epithelium to PIN and invasive carcinoma.
前列腺上皮内瘤变（PIN）是人类前列腺癌最可能的前体病变。虽然犬是唯一一种经常发生自发性前列腺癌的非人类物种，但犬前列腺中PIN的患病率尚不清楚。尚未描述PIN的自然发生动物模型。
为了确定高级别PIN是否在犬前列腺中自发发生，我们评估了35只无前列腺疾病临床证据的远交系犬的全包埋前列腺。分析了三组犬的前列腺：（1）11只7 - 17岁性成熟犬（老年性成熟犬）；（2）13只1 - 4岁性成熟犬（年轻性成熟犬）；（3）11只7 - 17岁已去势犬（老年去势犬）。通过对福尔马林固定、石蜡包埋的前列腺进行苏木精/伊红和高分子量角蛋白34β - E12染色组织切片的系统评估来确定PIN的患病率，这些切片以4毫米间隔连续切片。
犬高级别PIN表现出与人类对应病变相同的细胞学特征，包括细胞拥挤、极性丧失以及核和核仁增大。11只老年性成熟犬中有6只（55%）的前列腺存在高级别PIN病灶，但4岁以下的犬中只有1只（8%）有。11只老年去势犬中有1只（9%）检测到高级别PIN病灶。在有PIN的老年性成熟犬中，评估的83个组织切片中有13个（16%）存在高级别PIN病灶；其中一只犬除了PIN外还患有局灶性腺癌。
这些结果表明高级别PIN在老年性成熟犬的前列腺中经常存在。犬PIN的患病率与人类PIN一样，显然受年龄以及睾丸雄激素的影响。犬前列腺可能是一个有用的模型，用于确定调节从良性上皮向PIN和浸润性癌明显进展的因素。
