PCNA and Ki67 proliferation markers as criteria for prediction of clinical behaviour of melanocytic tumours in cats and dogs.

Melanocytic tumours in domestic animals vary from benign to highly malignant. Diagnosis and prognosis are mainly based on the somewhat uncertain interpretation of cytological signs of malignancy in histological sections. The purpose of the present retrospective study was to compare the accuracy of prognosis based on the classical morphological criteria with that provided by quantitative computerized analysis of proliferation-associated antigens. Twenty-seven melanocytic tumours (20 canine and seven feline) from 24 animals (20 dogs and four cats) were examined. These comprised eight tumours histologically classified as benign melanoma (BM) (seven canine, one feline), 16 classified as primary malignant melanoma (PMM) (13 canine, three feline) and three classified as metastatic melanoma (MMM) (three feline). Tumour size, predominant histological cell type, invasive growth and clinical outcome were recorded for each case. In addition, the proliferation (phase) index and growth fraction were measured, after bleaching, by means of quantitative image analysis of tissue sections immunolabelled for proliferating cell nuclear antigen (PCNA) and MIB-1 (Ki67). Lesions classified histologically as benign or malignant, differed significantly (Copyright P<0.001) in respect of Ki67 and PCNA positivity. No such difference could be shown between PMM and MMM. High growth fraction (measured by the Ki67 positive cells) and macroscopic invasive growth were associated with decreased survival time (P=0.027 and P=0.024, respectively). Moreover, the established cytological classification also proved to be associated with the survival time (P<0.001). The results suggest that Ki67 is a potentially important prognostic factor in melanomas of the cat and dog. Other criteria, including tumour size, predominant cell type and intensity of PCNA expression, were not of significant prognostic value (P>0.05). 1999 W.B. Saunders and Company Ltd.