This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Siitonen, S. M. Articles by Isola, J. J. Search for Related Content PubMed PubMed Citation Articles by Siitonen, S. M. Articles by Isola, J. J.

American Journal of Pathology, Vol 142, 1081-1089, Copyright © 1993 by American Society for Investigative Pathology

REGULAR ARTICLES

Proliferating cell nuclear antigen immunohistochemistry using monoclonal antibody 19A2 and a new antigen retrieval technique has prognostic impact in archival paraffin-embedded node-negative breast cancer

SM Siitonen, OP Kallioniemi and JJ Isola
Department of Biomedical Sciences, University of Tampere, Finland.

We evaluated whether proliferating cell nuclear antigen (PCNA) immunohistochemistry with antigen retrieval could be used as a measure of cell proliferation in archival, formalin-fixed, paraffin-embedded tissues and whether the staining results have long-term prognostic significance in axillary node-negative breast cancer. Primary tumor samples obtained from 109 axillary-node-negative breast cancer cases were used for the study. The best staining results were obtained with the 19A2 antibody after microwave heating in a solution of saturated lead thiocyanate. Using this method, there was a significant correlation (linear regression, r = 0.580, P < 0.001) between the proportion of PCNA19A2-positive carcinoma cells (PCNA19A2 score) and DNA flow cytometric S phase fraction. A high PCNA19A2 score was associated with high mitotic count, DNA aneuploidy, and absence of estrogen receptors. Axillary-node-negative patients with a high PCNA19A2 score (cut-point 8%) had significantly worse prognosis than those with a low PCNA19A2 score (P = 0.008). According to a Cox multivariate analysis, PCNA19A2 score had independent prognostic value but only if S phase fraction was excluded from the analysis. In our study, the PCNAPC10 score correlated weakly only with primary tumor size (analysis of variance) and prognosis (5-year univariate survival analysis), but the significance of these findings needs 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 breast carcinomas.

This article has been cited by other articles:

				J. R. Schultz-Norton, V. A. Gabisi, Y. S. Ziegler, I. X. McLeod, J. R. Yates, and A. M. Nardulli Interaction of estrogen receptor {alpha} with proliferating cell nuclear antigen Nucleic Acids Res., August 1, 2007; 35(15): 5028 - 5038. [Abstract] [Full Text] [PDF]

				P. Maffia, A. Ianaro, R. Sorrentino, L. Lippolis, F. M. Maiello, P. del Soldato, A. Ialenti, and G. Cirino Beneficial Effects of NO-Releasing Derivative of Flurbiprofen (HCT-1026) in Rat Model of Vascular Injury and Restenosis Arterioscler. Thromb. Vasc. Biol., February 1, 2002; 22(2): 263 - 267. [Abstract] [Full Text] [PDF]

				Y. Funakoshi, H. Nakayama, K. Uetsuka, R. Nishimura, N. Sasaki, and K. Doi Cellular Proliferative and Telomerase Activity in Canine Mammary Gland Tumors Vet. Pathol., March 1, 2000; 37(2): 177 - 183. [Abstract] [Full Text] [PDF]

				S.-R. Shi, R. J. Cote, and C. R. Taylor Antigen Retrieval Immunohistochemistry: Past, Present, and Future J. Histochem. Cytochem., March 1, 1997; 45(3): 327 - 344. [Abstract] [Full Text] [PDF]