CORRELATION OF GROWTH FRACTION BY KI-67 AND PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA) IMMUNOHISTOCHEMISTRY WITH HISTOPATHOLOGICAL PARAMETERS AND PROGNOSIS IN PRIMARY BREAST CARCINOMAS

The immunoreactivity for Ki-67 and PCNA was investigated in 487 patien ts with primary breast carcinomas using MIB-1 (Immunotech, France) and PC-10 (DAKO, Denmark) as primary antibodies. Formalin-fixed and paraf fin-embedded tissue sections were used. The immunoreactivity for Ki-67 and PCNA was found to be independent of the length of fixation if the sections were pretreated in a microwave oven in citrate buffer and di stilled water, respectively. The immunostaining was evaluated semiquan titatively. High Ki-67 score (more than 1% positive tumour cells) and PCNA over-expression (more than 25% positive tumour cells) were correl ated with clinicopathological parameters such as large tumour size, hi gh histological grade (poor differentiation), and absence of steroid h ormone receptors, which are parameters of an aggressive phenotype of t he tumour. In univariate analysis of survival data, both Ki-67 and PCN A were parameters of a poor overall survival in both lymph node-positi ve and -negative patients. In multivariate analysis using a Cox model stratified by nodal status, Ki-67 and PCNA failed to be of prognostic significance whereas classical histopathological parameters such as tu mour size and histological grade turned out to be of independent progn ostic significance in both lymph node-positive and -negative patients, while progesterone receptors were of independent prognostic significa nce only in lymph node-positive patients.