p63

Synonyms: TAp63

by Jan Klos

Background

P63 gene located on chromosome 3q27-28 encodes for multiple proteins arising from alternative splicing. It together with p53 and p73 belongs to same family, but has no tumor suppressor function. P63 protein plays an important role in regulating epithelial development and differentiation (transcription factor for squamous and urothelial differentiation). There are two isoforms used in diagnostic pathology: TAp63 recognizing full length of the protein and ΔNp63 (p40).

Staining in normal tissues

Restricted to certain cells and tissues: squamous epithelium, urothelium, basal cells in prostate acini and ducts, pseudostratified columnar epithelium, reserve cells of endocervix, pancreatic ducts, myoepithelium of breast, sweat glands and salivary glands as well as oocytes (but not testicular germ cells). The protein is expressed also by B-lymphocytes during transformation in germinal centers.

Staining in tumors

Squamous, urothelial and myoepithelial proliferations or components in different tumors. A subset of malignant B-cell lymphomas with the phenotype of follicular center cells (eg. FL and DLBCL) shows is positive for P63 but not for P40. Positive nuclear staining in a subset of ALK-negative cases of Anaplastic Large Cell Lymphoma (ALCL) may indicate rearrangement of the TP63 gene which is associated with aggressive course  and poor outcome of the disease.
Negative staining is seen in all mesenchymal cells including myofibroblasts, most of the lymphoid tissue (except germinal center cells), neural and neuroendocrine tissues as well as mesothelium

Staining pattern

Nuclear.

Control tissue

Placenta or tonsil.

Application

  • Distinction of invasive carcinoma (lack of staining in myoepithelial/basal cells) from non-invasive forms or its mimics.
  • In combination with other antibodies (CKHMW, AMCAR, CK5, CK5/6) may enhance the diagnostic accuracy in prostate biopsies.
  • Identification of poorly differentiated squamous carcinoma and transitional cell carcinoma.
  • Staining of myoepithelial cell component in biphasic tumors like pleomorphic adenoma, adenoid cystic carcinoma.
  • Positive staining in primary skin adnexal tumors may help in differential diagnosis against cutaneous metastases of adenocarcinoma.
  • Staining of thymic epithelial cells in thymoma.
  • Identification of both benign and malignant myoepithelial tumors
  • In lung tumors the positive staining confirms squamous differentiation however p40 (ΔNp63) is considered more specific for squamous differentiation

Selected references

  1. Barbareschi M, Pecciarini L, Cangi M G, et al. P63, a p53 Homologue, Is a Selective Nuclear Marker of Myoepithelial Cells of the Human Breast Am J Surg Pathol 2001 Aug;25(8):1054-60. PMID: 11474290  doi: 10.1097/00000478-200108000-00010. 
  2. Epstein J.I, Egevad L, Humphrey P.A. et al. Best practices recommendations in the application of immunohistochemistry in the prostate: report from the International Society of Urologic Pathology consensus conference. Am J Surg Pathol. 2014 Aug;38(8):e6-e19. PMID: 25029122. DOI: 10.1097/PAS.0000000000000238
  3. Ivan D, Hafeez Diwan A, Prieto VG. Expression of p63 in primary cutaneous adnexal neoplasms and adenocarcinoma metastatic to the skin. Mod Pathol. 2005 Jan;18(1):137-42. doi: 10.1038/modpathol.3800263. PMID: 15389254
  4. Langner C 1, Ratschek M, Tsybrovskyy O,  et al. P63 Immunoreactivity Distinguishes Upper Urinary Tract Transitional-Cell Carcinoma and Renal-Cell Carcinoma Even in Poorly Differentiated Tumors. J Histochem Cytochem. 2003 Aug;51(8):1097-9. doi: 10.1177/002215540305100813.
  5. Rollins-Raval M, Chivukula M, George C et al. An immunohistochemical panel to differentiate metastatic breast carcinoma to skin from primary sweat gland carcinomas with a review of the literature. Arch Pathol Lab Med. 2011 Aug;135(8):975-83. doi: 10.5858/2009-0445-OAR2.
  6. Wang X, Boddicker RL, Surendra Dasari S et al.   Expression of p63 protein in anaplastic large cell lymphoma: implications for genetic subtyping Hum Pathol. 2017 Jun;64:19-27.  doi: 10.1016/j.humpath.2017.01.003. Epub 2017 Jan 30. PMID: 28153507, PMCID: PMC5518937  DOI: 10.1016/j.humpath.2017.01.003
  7. Weinstein  MH, Signoretti S, Loda M. Diagnostic Utility of Immunohistochemical Staining for p63, a Sensitive Marker of Prostatic Basal Cells. Mod Pathol. 2002 Dec;15(12):1302-8.  doi: 10.1097/01.MP.0000038460.95912.6E.