RGD Reference Report - Expression of p53 protein in human middle ear cholesteatomas: pathogenetic implications. - Rat Genome Database

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Expression of p53 protein in human middle ear cholesteatomas: pathogenetic implications.

Authors: Albino, AP  Reed, JA  Bogdany, JK  Sassoon, J  Desloge, RB  Parisier, SC 
Citation: Albino AP, etal., Am J Otol. 1998 Jan;19(1):30-6.
RGD ID: 8547787
Pubmed: PMID:9455944   (View Abstract at PubMed)

BACKGROUND: Cholesteatoma is a destructive lesion of the middle ear or mastoid process or both. The molecular and cellular defects that result in the clinical hallmarks of acquired and congenital cholesteatomas, namely invasion, migration, uncoordinated proliferation, altered differentiation, aggressiveness, and recidivism, are unknown. Determining the existence of defects in the normal biology, biochemistry, and genetic complement of the major cellular constituents comprising a cholesteatoma (i.e., fibroblasts and keratinocytes) is critical to the understanding of the pathogenesis of cholesteatomas. It has been speculated that the development of human cholesteatomas is due, in part, to the altered control of cellular proliferation, which tilts the balance toward the aggressive, invasive growth of squamous epithelium within the middle ear. However, whether this altered control is due to defects in the mechanisms and underlying genes that control proliferation, or to cytokines released from infiltrating inflammatory cells, or to some other mechanism is unknown. The nuclear phosphoprotein p53 tumor suppressor gene plays a critical regulatory role in cell cycle control and apoptosis. In the current article, the authors have analyzed congenital, primary and secondary acquired, and recurrent cholesteatomas for the altered expression of p53 and Ki-67, a marker of active proliferation. METHODS: p53 and Ki-67 expression was determined by immunohistochemical assays using specific monoclonal antibodies. RESULTS: The authors' results indicate that p53 is elevated 9- to 20-fold in all cholesteatomas when compared to the expression of p53 in normal postauricular skin or tympanic membrane. However, there is no concomitant increase in Ki-67 expression in cholesteatomas. CONCLUSIONS: These data indicate a defect in cholesteatomas in the mechanisms that p53 engages (i.e., cell cycle control or apoptosis or both). In addition, these data further suggest that there is no intrinsic difference between any clinicopathologic group of cholesteatomas, at least with respect to p53-expression and, presumably, p53 function.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cholesteatoma of middle ear  IEP 8547787protein:increased expression:tympanic membrane and skin:RGD 
cholesteatoma of middle ear  ISOTP53 (Homo sapiens)8547787; 8547787protein:increased expression:tympanic membrane and skin:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tp53  (tumor protein p53)

Genes (Mus musculus)
Trp53  (transformation related protein 53)

Genes (Homo sapiens)
TP53  (tumor protein p53)


Additional Information