PROGNOSTIC VALUE OF THE COMBINED ASSESSMENT OF PROLIFERATING CELL NUCLEAR ANTIGEN IMMUNOSTAINING AND NUCLEAR-DNA CONTENT IN INVASIVE HUMAN MAMMARY CARCINOMAS

The expression of the S-phase associated, nuclear protein proliferatin g cell nuclear antigen (PCNA) was investigated in routinely paraffin-e mbedded surgical specimens from 209 breast cancer patients. Cytometric DNA assessments were performed on fine-needle aspirates, upon which t he primary diagnosis of breast cancer had been based. The mean clinica l follow-up was 16 years (range 13-20 years). The percentage of PCNA i mmunoreactive tumour cells ranged between less than 5 to 60% (mean val ue 13.34%). There was a direct association between PCNA expression, hi gh histological tumour grade (p < 0.01), and DNA aneuploidy (p = 0.009 ). In a subgroup of 22 patients with near-diploid DNA distribution pat terns the PCNA expression yielded additional prognostic information. P atients with tumours of near-diploid DNA histograms and more than 20% of PCNA immunoreactive neoplastic cells had a significantly worse clin ical course, than patients with near-diploid tumours containing less t han 20% PCNA immunoreactive cells (p = 0.0001). In contrast, the PCNA immunoreactivity did not yield additional prognostic information for p atients with distinctly diploid or highly aneuploid tumour variants. I n a multivariate analysis comprising all 209 patients, nodal status (p < 0.01), tumour size (p < 0.01), and DNA ploidy (p < 0.01) were found to have significant prognostic effect. The findings indicate that car cinomas characterised by high proliferative activity and near-diploid DNA distribution patterns can show rapid tumour progression. The combi ned assessment of the PCNA immunoreactivity and of the nuclear DNA con tent in routinely processed surgical specimens of breast cancer patien ts appears to be of prognostic value.