Expression of Prostaglandin E2 Receptors in Acquired Middle Ear Cholesteatoma

OBJECTIVES: To investigate the expression of prostaglandin E2 receptor subtypes, E-prostanoid (EP) 1–4 receptors, in acquired cholesteatoma and its possible role in the pathologic process of this disorder. METHODS: Specimens of human acquired cholesteatoma were obtained from 29 patients and 19 skin biopsies of normal external auditory canal were as controls. The mRNA and protein expression of EP receptors was assessed by quantitative real-time polymerase chain reaction, immunohistochemistry and Western blot. RESULTS: In acquired cholesteatoma, EP1–EP4 receptors were mainly expressed on squamous epithelium and subepithelial infiltrated inflammatory cells. In external auditory canal skin, EP1–EP4 receptors were mainly expressed on squamous epithelium and glandular epithelium. The expression of EP4 receptor on mRNA and protein levels were significant lower in acquired cholesteatoma compared with controls. EP1–EP3 receptors had no significant difference between the experimental and control group. CONCLUSION: Low expression of EP4 may play a crucial role in the pathologic process of inflammation reaction and bone destruction in acquired cholesteatoma, but not EP1, EP2, or EP3 receptors.

Etiología del colesteatoma ótico / Etiology of otic cholesteatoma

El colesteatoma es una estructura quística caracterizada por la presencia de epitelio escamoso productor de queratina, que sustituye o recubre la mucosa normal en la hendidura del oído medio y ápex petroso, y puede ser causa de hipoacusia irreversible, destrucción ósea y graves complicaciones por su crecimiento expansivo. Clásicamente se describen los colesteatomas en congénitos y adquiridos. La etiología de su formación es multifactorial y continúa siendo poco claro y controversial. Se reportan diferentes teorías que han tratado de explicar el colesteatoma congénito, la transición de un bolsillo de retracción hasta la aparición del colesteatoma adquirido primario, y otras en la génesis del colesteatoma adquirido secundario. Se describe la presencia de algunas citoquinas dentro del colesteatoma que inducen la hiperproliferación e invasión incoordinada de los queratinocitos de la piel del conducto auditivo externo y la pars fláccida, más agresiva en el colesteatoma adquirido pediátrico, y que desempeñan un papel fundamental en la proliferación y en la apoptosis del queratinocito. En cultivo in vitro de una muestra de tejido colesteatomatoso, se ha identificado recientemente que el TNF-a estimula la producción de la IL-8. Se considera de interés ofrecer esta revisión sobre la etiología del colesteatoma, que aún se mantiene en el campo de la investigación y continúa siendo un reto para los otocirujanos por su alta incidencia de recidivas y posibles complicaciones

Cholesteatoma is a cystic structure characterized by presence of squamous epithelium producing keratin substituting or recovering the normal mucosa in the groove of middle ear and petrous apex and may to be caused by irreversible hypoacusia, bone destruction and severe complications due to its expansive growth. Typically the cholesteatomas are described as congenital and acquired. The etiology of its formation is multifactor and still remains a subject not very clear and controversial. Different theories are reported to explain the congenital cholesteatoma, the transition of a retraction pocket until the appearance of primary acquired cholesteatoma and other on the genesis of the secondary acquired cholesteatoma. Presence of some cytokines in cholesteatoma is described inducing to hyperproliferation and not coordinated of keratinocytes of the external auditory meatus and the pars flaccida more aggressive in the pediatric acquired cholesteatoma playing a fundamental role in the proliferation and in apoptosis of keratinocyte. In a sample of choleastomatous tissue in vitro culture has been recently identified that the a-TNF stimulates the production of IL-8. It is interesting to offer present review on the etiology of cholesteatoma that still is under research and a challenge for otologists due to its high relapses incidence and potential complications