Characterization of patterns of expression of protein kinase C-α, -δ, -η, -γ and -ζ and their correlations to p53, galectin-3, the retinoic acid receptor-β and the macrophage migration inhibitory factor (MIF) in human cholesteatomas

Abstract Cholesteatoma is a benign disease characterized by the presence of an unrestrained growth and the accumulation of keratin in the middle ear cavity. Due to roles in cell proliferation, apoptosis and differentiation members of the protein kinase C (PKC) family could be involved in disease progression. This study focuses on the expression of protein kinase C-α, -δ, -η, -γ and -ζ in the epithelial tissues of 56 human cholesteatomas and their correlations with those of previously characterized distributions of p53, galectin-3, retinoic acid receptor-β (RARβ) and macrophage migration inhibitory factor (MIF). We have previously reported this marker set to be correlated with keratinocyte differentiation in human cholesteatomas. Our present data clearly show that the percentage of PKC-α (but not PKC-δ, -γ, -η and -ζ)-immunopositive cells in epithelial tissue fro recurrent cholesteatomas was significantly higher than in non-recurrent cases. Correlations between the PKC isoenzymes and the biological markers were non-uniform. PKC-α (but not PKC-δ, -γ, -η and -ζ) expression in epithelial cholesteatoma cells correlated significantly and positively with the percentages of p53-immunopositive cells. The patterns of PKC-α and -δ expression, but not of PKC-γ, -η and -ζ, correlated significantly and positively with galectin-3 expression. In addition, the correlation levels between the expression of PKC-α and -δ and that of galectin-3 varied depending on the infection and recurrence status. Presence of RARβ correlated significantly (and positively) with the expression of PKC-γ and -ζ and also in relation to the infection and recurrence status. MIF correlated presence significantly (and positively) with that of the five PKCs under study, depending on whether the cholesteatomas were non-infected or infected as well as non-recurrent or recurrent. In conclusion, the present study suggests that modifications occurring at the level of keratinocyte differentiation in human cholesteatomas involve distinct effectors, to which the activation of PKC-α, -δ, -η, -γ and -ζ can be added.