Cell proliferation in breast tumours: analysis of histological parameters Ki67 and PCNA expression

Ki67 and Proliferating Cell Nuclear Antigen (PCNA) are antigens expressed in the nucleus during various phases of cell division, which can be detected immunohistochemically using monoclonal antibodies. Thirteen fibroadenomas and 39 carcinomas were examined for expression of Ki67 and PCNA. A staining index was calculated for each tumour as the percentage of positive cells in the areas of highest density. The mean index for both antibodies was significantly lower in fibroadenomas than in malignant tumours. A wide range of proliferation rates was seen in the malignant group; the mean Ki67 index of Grade I carcinomas was 9% +/- 4.4 (mean +/- SD), of Grade II 14.3 +/- 8.7 and of Grade III 26.2 +/- 15.7. These differences are statistically significant. In malignant tumours there was a good correlation between the mitotic count and the Ki67 index (r = 0.61, p < 0.005) but none between the mitotic count and PCNA index. There was a weak correlation between the Ki67 and the PCNA indices (r = 0.38 p < 0.005), but no correlation was found between either index and oestrogen receptor status, patient age or tumour size. Ki67 immunohistochemistry is a convenient method for assessing cell proliferation, applicable in most laboratories. The validity of measuring proliferation in this way has yet to be established but the wide variation of expression even within the conventional grading categories may help to discriminate prognostically distinct subgroups. Expression of PCNA appears to correlate poorly with Ki67 expression in breast tumours and not with mitotic count; therefore its usefulness as a marker of proliferative activity, on current evidence, appears to be limited.