Ribeiro-Silva Alfredo, Zambelli Ramalho Leandra N, Britto Garcia Sérgio, Zucoloto Sérgio
Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo (FMRP/USP), São Paulo, Brazil.
Arch Pathol Lab Med. 2003 Mar;127(3):336-40. doi: 10.5858/2003-127-0336-TRBPAP.
p63 is a recently described p53 homologue. Despite structural homology, they have different activities.
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.
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 34betaE12. Clinical data were retrieved from medical files.
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 34betaE12, but not cytokeratin 7. Expression of p63 correlated with pathologic staging, tumor size, histologic grading, nodal metastasis, and estrogen receptor negativity.
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.
p63是最近发现的一种p53同源物。尽管在结构上具有同源性，但它们具有不同的活性。
深入了解p63在正常乳腺组织和肿瘤性乳腺组织中的作用，并验证p63与乳腺癌中p53之间可能存在的关联。
对85例乳腺癌进行免疫组织化学检测，检测指标包括p63、平滑肌肌动蛋白（1A4）、p53、雌激素受体和孕激素受体。对p63阳性病例进行p63与1A4、细胞角蛋白7和34βE12的双重免疫标记研究。从病历中获取临床数据。
p63与1A4一样，染色正常乳腺导管和腺泡上皮周围的单层连续细胞层。在癌组织中，21.17%的癌组织表达p53，而p63仅在低分化导管癌中表达（占病例的11.76%）。p63阳性细胞共表达1A4和34βE12，但不表达细胞角蛋白7。p63的表达与病理分期、肿瘤大小、组织学分级、淋巴结转移和雌激素受体阴性相关。
p63是正常乳腺组织中一种特异性的肌上皮细胞标志物，仅在少数乳腺癌中表达，且仅见于Ⅲ级导管癌。在导管癌中，恶性p63阳性细胞具有与肌上皮细胞相似的免疫表型，提示这些细胞起源于克隆扩增过程中经历向导管细胞和肌上皮细胞分化的原始祖细胞。我们的研究反对其在乳腺肿瘤发生中起直接作用。然而，p53很少与p63共表达，提示p63可能通过抑制p53间接发挥癌基因作用。这一假说也可以解释为什么p63与其他几个预后不良指标相关。
