title: Expressions of matrix metalloproteinase-9 (MMP-9), dentin sialophosphoprotein (DSPP), and osteopontin (OPN) at histologically negative surgical margins may predict recurrence of oral squamous cell carcinoma.
abstract: Up to 50% of oral squamous cell carcinomas (OSCCs) recur following surgical resections with conventional "histologically-negative" margins. Three members of the SIBLING family of proteins: dentin sialophophoprotein (DSPP); bone sialoprotein (BSP); and osteopontin OPN are upregulated in OSCCs. In this study, we aimed to correlate the expression of DSPP, OPN and BSP as well as three SIBLING-partners, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-9 (MMP-9), at histologically-negative margins of OSCCs with tumor recurrence. Immunohistochemical analyses of the SIBLINGs and MMP expressions at histologically-negative margins of OSCC was carried out in a retrospective study of 20 patients, and the results correlated with tumor recurrence. Each protein was dichotomized as "present" (≥10% staining) or "absent" (more than 10% staining). The Sensitivity, Specificity, Positive Predictive Value(PV+) and Negative Predictive Value (PV-) for recurrence was calculated for each protein, along with their overall diagnostic accuracy, calculated as: (number of true positives + number of true negatives)/ number of patients. OSCC recurred in 9 of 20 patients (45%), a ratio not significantly different from the estimated population recurrence rate of 50% (p = 0.664). Among the SIBLINGs, DSPP and OPN showed the greatest Accuracy with DSPP being more Sensitive (89%) and OPN more Specific (64%). MMP-9 showed the greatest overall Accuracy (80%), slightly less Sensitivity (67%) and more Specificity (100%), than either DSPP or OPN. MMP-9 showed a superior positive PV than either DSPP or OPN. The negative PVs of OPN and MMP-9 were almost identical, and inferior to DSPP. We conclude that DSPP, OPN, or MMP-9 expressions at histologically-negative surgical margins predict OSCC recurrence with MMP-9 being the preferred predictor. These proteins may identify patients who could benefit from more extensive resection, or from adjunct treatments such as radiotherapy.
authors.affiliation: College of Dental Medicine, Georgia Health Sciences University, Augusta, GA, USA. kogbureke@georgiahealth.edu
authors.forename: Kalu U E
authors.initials: KU
authors.lastname: Ogbureke
authors.forename: Paul M
authors.initials: PM
authors.lastname: Weinberger
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Looney
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Larry W
authors.initials: LW
authors.lastname: Fisher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D012795:Sialoglycoproteins / Q000378:metabolism*; D000099311:Dentin Sialophosphoprotein
chemical_list: D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D020780:Matrix Metalloproteinase 9; D053495:Osteopontin; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein