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

Up to 50% of oral squamous cell carcinomas (OSCCs) recur following surgical resections with conventional "histologically-negative" margins. Three members of the SIBLING (Small Integrin Binding LIgand N-linked Gylcoprotein) 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" (< 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.