Localization of matrix metalloproteinase 1 in cholesteatoma and deep meatal skin.

ABSTRACT

HYPOTHESIS: Matrix metalloproteinase 1 (MMP-1) is overexpressed in cholesteatoma. BACKGROUND: Cholesteatoma destroys bone, whereas deep meatal skin does not. MMP-1 is a type I collagenase that may be responsible for this destruction. This prospective study was designed to identify overexpression of MMP-1 by cholesteatoma in comparison with deep meatal skin. METHODS: Ten cholesteatoma specimens and nine deep meatal skin specimens were removed during otologic surgery and then fixed in formalin and embedded in paraffin. Immunocytochemistry studies were performed using a monoclonal antibody to MMP-1. A pathologist assessed the slides in a blinded fashion. Expression of MMP-1 protein in epidermis and in stroma was scored from 0 to 10. Five further cholesteatoma specimens and three deep meatal skin specimens underwent reverse transcriptase polymerase chain reactions to assess messenger ribonucleic acid production. Paired and unpaired Student's t tests were used to assess the difference in expression levels. RESULTS: Cholesteatoma stroma expressed significantly more MMP-1 protein than did deep meatal skin stroma (p = 0.04). MMP-1 was localized to stromal fibroblasts. There was no difference in the epidermal expression levels of the two tissue types (p = 0.42). The reverse transcriptase polymerase chain reaction showed expression at the messenger ribonucleic acid size of MMP-1 (262 base pair) in all cholesteatoma specimens examined. One deep meatal skin specimen showed a weak signal; no signal was seen in the other specimens. CONCLUSIONS: MMP-1 is overexpressed by the stromal fibroblasts present in cholesteatoma as compared with deep meatal skin. It is possible that these cells rather than the keratinocytes are responsible for bone destruction in this disease.