Matrix metalloproteinase 7 and perlecan in oral epithelial dysplasia and carcinoma in situ: an aid for histopathologic recognition of their cell proliferation centers.
BACKGROUND
As one of the valuable tools for differential diagnoses of oral epithelial dysplasia, carcinoma in situ (CIS) and squamous cell carcinoma (SCC), we have proposed the immunohistochemistry for perlecan, a heparan sulfate proteoglycan (HSPG). As HSPGs have been shown to be extracellular docking molecules for matrix metalloproteinase (MMP) 7, our aim was to determine the expression mode of MMP-7 in these lesions for its possible diagnostic aid for oral borderline malignancies.


METHODS
Twenty cases each of moderate dysplasia, CIS, SCC, and normal/hyperplastic/mild dysplastic epithelia of the tongue and buccal mucosa were immunohistochemically examined for MMP-1, -2 and -7 in reference to their perlecan immunolocalization.


RESULTS
The expression of all three MMPs in the normal mucosal epithelium was restricted mainly to the parabasal layers. The most striking finding was strong expression of MMP-7 in epithelial dysplasia with a two-phase appearance: a clear demarcation of MMP-7-immunopositive (+) lower dysplastic/basaloid cells from non-positive upper keratinized cells. MMP-7+ cells were spread over the whole epithelial layer of CIS. In SCC, MMP-7 positivity was reduced from carcinoma cells but instead appeared in stromal cells. These expression profiles of MMP-7 resembled those of perlecan. MMP-1 and MMP-2 exhibited a similar but much weaker staining than MMP-7.


CONCLUSIONS
These results suggest that the enhanced metabolism of perlecan associated with MMP-7 plays an important role in the cell proliferation of oral epithelia in their malignant transformation process, and that MMP-7 immunohistochemistry may be a valuable aid for identification of the cell proliferation center in oral CIS and dysplasia.
Tilakaratne
W M
WM
Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Kobayashi
T
T
Ida-Yonemochi
H
H
Swelam
W
W
Yamazaki
M
M
Mikami
T
T
Alvarado
C G
CG
Shahidul
A Md
AM
Maruyama
S
S
Cheng
J
J
Saku
T
T
D002278:Carcinoma in Situ / Q000175:diagnosis / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003937:Diagnosis, Differential; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000175:diagnosis / Q000378:metabolism*; D014062:Tongue Neoplasms / Q000175:diagnosis / Q000378:metabolism*
D019812:Heparan Sulfate Proteoglycans; C071927:perlecan; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1