p40

Characteristics

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 exists in two isoforms: TAp63, which is a p53 like tumour suppressor, and ?Np63, which is an oncogene. p40 (originally an antibody against the ?N domain of p63, but now used as a synonym) is the predominant p63 isotype in basal/progenitor cells.

Neoplasms

+: >90% positive, +/-: 50-90% positive, -/+: 10 - >50% positive, -(+): 1-<10% positive, -: <1% positive, ?: conflicting evidence or insufficient information.
+ Squamous cell carcinoma (85-100%), Urothelial carcinoma (80-100%).
-(+) Rare cases of lung adenocarcinoma (~3%) express focal p40.

Application

Among carcinomas, p40 has approximately the same sensitivity as p63 but a higher specificity, as the TAp63 isoform is expressed more widespread in eg., adenocarcinomas. Moreover, p63 occur in lymphomas that are p40 negative.

Controls

Placenta is recommended as positive tissue control for p40, where an at least weak to moderate, distinct nuclear staining reaction of cytotrophoblasts must be seen. The cytotrophoblasts should be visible even at low magnification (5x objective).
Supportive to placenta, tonsil can be used as positive and negative tissue control. Virtually all squamous epithelial cells must show a moderate to strong, distinct nuclear staining reaction. No nuclear or cytoplasmic staining reaction should be seen in other cell types. 

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