DETECTION OF P53 EXPRESSION AND S-PHASE CELL FRACTION IN PARAFFIN-EMBEDDED TISSUE BY A DOUBLE-LABELING TECHNIQUE

TP53 is a gene that normally regulates cell growth and division, Alter ations to it may induce a proliferative advantage and confer an aggres sive phenotype, In breast cancer, we observed a poor correlation (r(s) = 0.17) between P53 expression and proliferative activity evaluated a s [H-3]-thymidine ([H-3]-dT) labeling index and an independent prognos tic relevance of the two variables. We used a double-labeling techniqu e to simultaneously evaluate the fraction of P53-positive and [H-3]-dT -labeled cells to analyte the degree of association between the two ma rkers on individual cells in order to understand their biological sign ificance, The study was performed on a series of 44 P53-positive (P53( +)) breast cancers. Histological sections were immunostained for P53 w ith monoclonal antibody (MAb) PAb1801 and then processed for autoradio graphy. A weak direct relation between P53 positivity and [H-3]-dT inc orporation (r(s) = 0.4) was observed on the overall series of P53(+) t umors and was maintained in subgroups defined by several biological an d pathological features, except for estrogen receptor-negative tumors, The simultaneous presence of P53 expression and [H-3]-dT incorporatio n was directly and significantly proportional to the fraction of S-pha se cells of the tumor (r(s) = 0.7). Conversely, the fraction of cells expressing only P53 was inversely related to cell proliferation (r(s) = -0.66). These findings support the hypothesis that P53 has biologica l functions other than cell cycle regulation.