Comparison of proliferative activity as assessed by proliferating cell nuclear antigen (PCNA) and Ki‐67 monoclonal antibodies in melanocytic skin lesions

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Abstract
Immunostaining with the monoclonal antibodies PCNA and Ki-67 provides a simple method for the assessment of growth fractions of tumors. Contrary to Ki-67, PCNA antibody can be applied on aldehyde- or alcohol-fixed and paraffin-embedded tissues, thus allowing studies on archival material. For 77 melanocytic skin lesions, we compared PCNA immunostaining on formalin-fixed tissue with Ki-67 immunostaining on frozen material of the same lesion. 16 benign melanocytic nevi (BMN, from 16 patients), 43 primary malignant melanomas (PMM, 42 patients), and 18 skin mclastases of malignant melanoma (MMM, 12 patients) were included in the study. Maximum nuclear density (NDmax) of PCNA- and Ki-67-positivc nuclei was assessed using interactive image analysis. NDmax values for both PCNA and Ki-67 differed significantly between the three diagnostic groups (Kruskal-Wallis H-test: p ≪ 0.001). Mean values (given as 1000 nuclei/mm1 tissue) increased considerably from benign lo malignant lesions (PCNA: BMN: 23.8 ± 28.4 [mean ± standard deviation], PMM: 48.1 ± 41.0, MMM: 117.0 ± 64.6; Ki-67: BMN: 6.4 ± 3.3, PMM 25.0 ± 31.1, MMM: 95.2 ± 47.2). Correlation between NDmax values of PCNA- and Ki-67-positive nuclei was significant (Linear regression analysis: r = 0.51, p ≪ 0.001). Furthermore, for PMM a significant correlation between histologic parameters related to prognosis (Breslow index and mitotic rate) and PCNA as well as Ki-67 expression was found (PCNA – Breslow index: r = 0.42, p < 0.01; Ki-67 – Breslow index: r = 0.60, p ≪ 0.001; PCNA – mitotic rale: r = 0.40, p <.0.01; Ki-67 – milotic rale: r = 0.50, p < 0.001). Concerning patients' survival, NDmax values of PCNA – and Ki-67-posilive nuclei as a single prognostic parameter were not superior to Breslow index. We conclude that PCNA and Ki-67 expression as assessed by interactive image analysis may be suitable for tumor grading in melanocytic skin lesions. The relevance of these parameters for prognosis remains to be determined by long-term follow-up studies.