p63 protein (p63) is a nuclear protein, a transcription factor. The p63 gene is located at chromosome 3q27-29 and belongs to the p53 gene family. p63 plays a critical role in the growth and development of many epithelial organs. p63 is confined to basal cells of squamous epithelia (including epidermis and hair follicles) and urothelium, as well as basal cells/myoepithelial cells in breast, sweat glands, salivary glands, and prostate.
p63 is found in the large majority of cases of squamous cell carcinoma (even among low differentiated squamous carcinomas, more than 70% of the cases are positive) as well as adenosquamous carcinoma, urothelial carcinoma, myoepithelial carcinoma, adenoid cystic carcinoma and skin adnexal tumours (cylindroma, eccrine poroma, syringoma, trichoepithelioma, trichilemmoma, spiradenoma). Also metaplastic carcinoma and sarcomatoid carcinoma is frequently positive as are signet ring cell carcinoma of salivary gland and anaplastic thyroid carcinoma. Moreover p63 has been detected in adenocarcinomas of e.g., lung and pancreas (possibly as an expression of squamous differentiation that is not recognized histologically) as well as in colon adenocarcinoma with morule formation (probably a stem cell proliferation rather than squamous differentiation). In basal-like subtype breast carcinoma, p63 is rarely detected. Prostate adenocarcinoma is almost always p63 negative, although low differentiated carcinomas may reveal a weak staining. Among non-epithelial neoplasms p63 has been revealed in epithelioid sarcoma and rare cases of other sarcomas.
In carcinomas p63 is a very useful marker for squamous, urothelial and myoepithelial differentiation. The same tumours are usually expressing cytokeratin 5. However, p63 often shows a more extended reaction. An important criterion for the diagnosis of prostate adenocarcinoma is the absence of basal cells. As these can be difficult to identify in routine sections, immunohistochemical identification of p63 and cytokeratin 5 may increase the sensitivity and specificity. Since negative staining for high molecular weight cytokeratin (HMW-CK) in atypical prostate glands may not be sufficient for a definitive diagnosis of malignancy, p63 may enhance the ability to diagnose limited prostate cancer. However, p63 should be used in conjunction with HMW-CK and AMACR. A cocktail staining is applicable. The combination of p63 and HMW-CK increases the sensitivity of basal cell detection.
Placenta is recommended as primary and critical positive tissue control for p63 where an at least weak to moderate, distinct nuclear staining reaction of dispersed cytotrophoblasts must be seen. The cytotrophoblasts should be visible even at a low magnification (5x objective). Tonsil can serve as both supplementary positive and also as negative tissue control. In tonsil virtually all squamous epithelial cells must show a moderate to strong, distinct nuclear staining reaction, while dispersed lymphocytes and endothelial cells must show a weak but distinct staining reaction. The vast majority of lymphocytes should be negative.
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