COMPARISON OF PROLIFERATIVE ACTIVITY AS ASSESSED BY PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA) AND KI-67 MONOCLONAL-ANTIBODIES IN MELANOCYTIC SKIN-LESIONS - A QUANTITATIVE IMMUNOHISTOCHEMICAL STUDY

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 metastases of malignant melanoma (MMM, 12 patients) were included in the study. Maximum nuclear density (ND(max)) of PCNA- and Ki-67-positive nuclei was assessed using interactive image analysis. ND(max) values for both PCNA and Ki-67 differed significantly between the three diagnostic groups (Kruskal-Wallis H-test: p much less than 0.001). Mean values (given as 1000 nuclei/mm3 tissue) increased considerably from benign to 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 ND(max) values of PCNA- and Ki-67-positive nuclei was significant (Linear regression analysis: r = 0.51, p much less than 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 < 0.0 1; Ki-67-Breslow index: r = 0.60, p much less than 0.001; PCNA - mitotic rate: r = 0.40, p < 0.01; Ki-67 - mitotic rate: r = 0.50, p < 0.001). Concerning patients' survival, ND(max) values of PCNA- and Ki-67-positive 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.