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. Alterations to it may induce a proliferative advantage and confer an aggressive phenotype. In breast cancer, we observed a poor correlation (rs = 0.17) between P53 expression and proliferative activity evaluated as [3H]-thymidine ([3H]-dT) labeling index and an independent prognostic relevance of the two variables. We used a double-labeling technique to simultaneously evaluate the fraction of P53-positive and [3H]-dT-labeled cells to analyze the degree of association between the two markers on individual cells in order to understand their biological significance. The study was performed on a series of 44 P53-positive (P53+) breast cancers. Histological sections were immunostained for P53 with monoclonal antibody (MAb) PAb1801 and then processed for autoradiography. A weak direct relation between P53 positivity and [3H]-dT incorporation (rs = 0.4) was observed on the overall series of P53+ tumors and was maintained in subgroups defined by several biological and pathological features, except for estrogen receptor-negative tumors. The simultaneous presence of P53 expression and [3H]-dT incorporation was directly and significantly proportional to the fraction of S-phase cells of the tumor (rs = 0.7). Conversely, the fraction of cells expressing only P53 was inversely related to cell proliferation (rs = -0.66). These findings support the hypothesis that P53 has biological functions other than cell cycle regulation.
Benini
E
E
Istituto Nazionale per lo Studio e la Cura dei Tumori, Oncologia Sperimentale C, Milano, Italia.
Silvestrini
R
R
Daidone
M G
MG
Canova
S
S
D000911:Antibodies, Monoclonal; D001345:Autoradiography; D001943:Breast Neoplasms / Q000473:pathology* / Q000601:surgery; D002453:Cell Cycle; D002455:Cell Division; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008940:Mitotic Index; D010232:Paraffin; D011960:Receptors, Estrogen / Q000032:analysis; D012044:Regression Analysis; D016196:S Phase; D013194:Staining and Labeling / Q000379:methods; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53; D014316:Tritium; D010232:Paraffin; D013936:Thymidine