The Relationship Between p63 and p53 Expression in Normal and Neoplastic Breast Tissue

Abstract

Abstract Context.—p63 is a recently described p53 homologue. Despite structural homology, they have different activities. Objectives.—To obtain new insights into the role of p63 in normal and neoplastic breast tissue and to verify the possible association between p63 and p53 in breast carcinomas. Design.—Immunohistochemistry in 85 breast carcinomas using p63, smooth muscle actin (1A4), p53, estrogen receptor, and progesterone receptor. The p63-positive cases were submitted to a double-immunolabeling study using p63 with 1A4, cytokeratin 7, and 34βE12. Clinical data were retrieved from medical files. Results.—p63, like 1A4, stained a single and continuous layer surrounding normal breast ductal and alveolar epithelium. In carcinomas, p53 was expressed in 21.17% of carcinomas, whereas p63 was expressed only in poorly differentiated ductal carcinomas (11.76% of cases). p63-positive cells coexpressed 1A4 and 34βE12, but not cytokeratin 7. Expression of p63 correlated with pathologic staging, tumor size, histologic grading, nodal metastasis, and estrogen receptor negativity. Conclusions.—p63 is a specific myoepithelial cell marker in normal breast tissue and is expressed in a minority of breast carcinomas, being seen only in grade III ductal carcinomas. In ductal carcinomas, malignant p63-positive cells have an immunophenotype similar to that of myoepithelial cells, suggesting that these cells originate from a primary progenitor cell that underwent divergent differentiation to ductal and myoepithelial cells during clonal expansion. Our study argues against a direct role in mammary tumorigenesis. However, p53 is rarely coexpressed with p63, suggesting that p63 could act indirectly as an oncogene by inhibiting p53. This hypothesis could also explain why p63 correlated with several other indicators of poor prognosis.