Immunohistochemical analysis of p27 and p21 proteins in canine mammary tumors
Veterinary Pathology Department, Yamaguchi University, Yamaguchi, Yamaguchi, Japan
AIM: The cell cycle progression is strictly regulated by cyclin-dependent kinases (CDKs). The p27 and p21, which belong to the CIP/KIP family of CDK inhibitors, can inhibit several CDKs. Dysregulated expression of p27 and p21 has been shown to be associated with tumor development and progression. Mammary tumors are the most common neoplasms in the dog and the common types are the compex type tumor and carcinoma. The object of this study was to evaluate p27 and p21 expression in mammary gland tumors of dogs. METHODS: Sixty-four canine mammary tumors (11 simple type adenomas, six complex type adenomas, 35 simple type carcinomas, nine complex type carcinomas, and three malignant myoepitheliomas) were examined for p27 and p21 expression by quantifying nuclear immunohistochemical staining, using a biotin-streptavidin immunoperoxidase method. The extent of the nuclear reactivity was classified as either absent, slight, focal (1-10% of tumor cells), moderate (10-50%) or intense (50-100%). RESULTS: Each of 11 simple type and six complex type adenomas showed intense reactivity with p27. The myoepithelial component in complex type adenomas showed intense reactivity. Six of 35 simple type carcinomas showed no detectable p27 reactivity, and 13 showed moderate reactivity, although 16 cases showed intense reactivity. Three of nine complex type carcinomas showed slight, focal p27 reactivity, and five showed moderate reactivity, while one showed intense reactivity. The reactivity of the myoepithelial component was slight, focal or moderate in eight of nine complex type carcinomas. Three malignant myoepitheliomas showed no detectable or moderate p27 reactivity. Decreased expression of p27 protein was revealed in the malignant tumors. In contrast to p27, nine of 11 simple type adenomas, six complex type adenomas, 26 of 35 simple type carcinomas, eight of nine complex type carcinomas, and three malignant myoepitheliomas showed no detectable or slight, focal reactivity with p21. The myoepithelial component showed no detectable p21 reactivity. However, two simple type adenomas and 10 carcinomas showed moderate or intense p21 reactivity. Histologically, squamous metaplasia of the epithelial component was seen in various degrees in the p21 positive cases. Solid sheets of cells with central keratinization and formation of small sized keratin pearls appeared. High levels of expression of p21 were limited in the area of squamous metaplasia. CONCLUSIONS: Decreased expression of p27 was principally associated with the progression of malignancy in mammary tumorigenesis of dogs. Expression of p21 was involved in squamous metaplasia of the epithelial component, but not in the tumor progression.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 892 (Susceptibility genes).