PROLIFERATING CELL NUCLEAR ANTIGEN IMMUNOHISTOCHEMISTRY USING MONOCLONAL-ANTIBODY 19A2 AND A NEW ANTIGEN RETRIEVAL TECHNIQUE HAS PROGNOSTICIMPACT IN ARCHIVAL PARAFFIN-EMBEDDED NODE-NEGATIVE BREAST-CANCER

We evaluated whether proliferating cell nuclear antigen (PCNA) immunoh istochemistry with antigen retrieval could be used as a measure of cel l proliferation in archival, formalin-fixed paraffin-embedded tissues and whether the staining results have long-term prognostic significanc e in axillary node-negative breast cancer. primary tumor samples obtai ned from 109 axillary-node-negative breast cancer cases were used for the study. The best staining results were obtained with the 19A2 antib ody after microwave heating in a solution of saturated lead thiocyanat e. Using this method, there was a significant correlation (linear regr ession, r = 0.580, P < 0.001) between the proportion of PCNA19A2-posit ive carcinoma cells (PCNA19A2 score) and DNA flow cytometric S phase f raction. A high pCNA19A2 score was associated with high mitotic count, DNA aneuploidy, and absence of estrogen receptors. Axillary-node-nega tive patients with a high PCNA19A2 score (cut-point 8%) bad significan tly worse prognosis than those with a low PCNA19A2 score (P = 0.008). According to a Cox multivariate analysis, PCNA19A2 score bad independe nt prognostic value but only if S phase fraction was excluded from the analysis. In our study, the PCNA(PC10) score correlated weakly only w ith primary tumor size (analysis of variance) and prognosis (5-year un ivariate survival analysis), but the significance of these findings ne eds further evaluation. In conclusion, PCNA immunohistochemistry with the 19A2 antibody after an appropriate antigen retrieval treatment may offer a useful alternative to DNA flow cytometry for the analysis of cell proliferation activity from formalin-fixed, paraffin-embedded bre ast carcinomas.