The Role Of KGF/KGFR Expression In Hyperplasia And Keratinization Of External Auditory Canal Epithelium In Keratosis Obturans

Objective : Keratosis obturans(KO)is embolism caused by abnormal keratin accumulation in the bony segment of external auditory canal(EAC).It can cause tinnitus,sense of blocking,conductive hearing loss and other symptoms.Because of its frequent attacks,it needs long-term and regular physical cleaning,which brings serious inconvenience to patients.In This study we selected 1 case of keratosis obturans,performed pathological examination on the keratin cast and epithelium of the EAC,then assessed the expression of keratinocyte growth factor(KGF)and keratinocyte growth factor receptor(KGFR)and Ki-67 in the KO epithelium.With cholesteatoma and normal EAC epithelium used as comparison,we discovered the differences between them,and made experimental treatments based on the results in hope of cure.Method:In this study we obtained 1 case of keratin cast and EAC epithelium of the patient who have been diagnosised as KO and need frequent and periodic cleaning at the department of Otolaryngology of the Fourth Affiliated Hospital of China Medical University.Besides,we selected 9 case of cholesteatoma and 3 case of normal EAC skin from patients who were performed surgery between June and September.Hematoxylin-eosin(HE)staining and immunohistochemical method were used to compare the difference between them,and we made experimental treatments by glucocorticoid(dexamethasone)based on the results.Results:1.In the keratin cast and EAC epithelium of KO,HE staining showed significant Hyperkeratosis with parakeratosis,acanthosis cell layer thickening,parsbasilaris downward extension to the in-depth dermis,and dermal lymphocytes infiltrate as well.The histological structure of cholesteatoma was that loose keratin fragments are encased in thickened squamous epithelium,the stroma contains varying numbers of lymphocyte infiltrates.The normal EAC skin was uniform in thickness,regular in shape and well differentiated,with almost no inflammatory cell infiltration in the dermis.2.Immunohistochemical results: ○1 In the case of KO epithelium,KGF/KGFR expression was strongly positive(+++),while the Ki-67 expression was positive(++).○2 In the cholesteatoma group,KGF expression was strongly positive(+++)in 2cases,positive(++)in 5 cases and weakly positive(+)in 2 cases.KGFR expression was strongly positive(+++)in 4 cases,positive(++)in 5 cases,Ki-67 expression was positive(++)in 4 cases,weakly positive(+)in 5 cases.○3 In the normal EAC skin,KGF expression was positive(++)in 1 case and weakly positive(+)in 2 cases.KGFR expression showed positive(++)in 1 case,weakly positive(+)in 2 cases.Ki-67 expression was all weakly positive in 3 cases.3.After 3 weeks of external treatment with glucocorticoid(dexamethasone),the hyperemia and swelling of external auditory canal epithelium and tympanum was significantly reduced,and no keratin cast were formed.Conclusion:1.Unlike cholesteatoma,KO is diffuse inflammation of the bony segment EAC epithelium caused by certain factors,resulting a large number of inflammatory cell infiltration in the dermis,thickening of the squamous epithelium,and vertical hyperkeratosis with or without parakeratosis,which is characterized by long-term and frequent formation of keratin cast in the external auditory canal.2.Increased expression of KGF/KGFR and Ki-67 indicates that the activity of the squamous epithelium,lymphocytes and dermis fibroblasts was enhanced.This paracrine effect of KGF leading to excessive proliferation of basal layer cells,and make the stratum spinosum,granular layer cells can’t complete the terminal differentiation,and then show the hyperkeratosis with parakeratosis.3.Glucocorticoids and inhibitors to the KGFR can inhibit the effect of KGF/KGFR and have therapeutic significance for keratosis obturans.