Hypothesis: Matrix metalloproteinase I (MMP-1) is overexpressed in choleste
atoma.
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 b
y cholesteatoma in comparison with deep mental skin.
Methods: Ten cholesteatoma specimens and nine deep meatal skin specimens we
re 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 u
nderwent reverse transcriptase polymerase chain reactions to assess messeng
er ribonucleic acid production. Paired and impaired Student's t tests were
used to assess the difference in expression levels.
Results: Cholesteatoma stroma expressed significantly more MMP-1 protein th
an did deep meatal skin stroma (p = 0.04). MMP-1 was localized to stromal f
ibroblasts. There was no difference in the epidermal expression levels of t
he 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 sk
in specimen showed a weak signal; no signal was seen in the other specimens
.
Conclusions: MMP-1 is overexpressed by the stromal fibroblasts present in c
holesteatoma as compared with deep meatal skin. It is possible that these c
ells rather than the keratinocytes are responsible for bone destruction in
this disease.