DSPP, OPN, and MMP-9 expression at surgical-margins predict OSCC recurrence

Objective: 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 OSCC. This study aimed to correlate the expression of DSPP, OPN and BSP, and the three SIBLING-partnering MMPs: MMP-2; MMP-3; and MMP-9 at histologically-negative margins of OSCCs with tumor recurrence. Methods: Immunohistochemical analysis of BSP, DSPP, OPN, MMP-2 MMP-3, and MMP-9 expressions at histologically-negative margins of OSCC was carried out in a retrospective study of 20 patients, and expressions correlated with tumor recurrence. Each protein was dichotomized as present or absent; "present" defined as ≥10% staining and "absent" as < 10% staining. The Sensitivity, Specificity, Predictive Value-positive (PV+) and Predictive Value-negative (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. Results: OSCC recurred in 9 of the 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%). MMP9 showed the greatest overall Accuracy (80%), slightly less Sensitive (67%) and more Specific (100%), than either DSPP or OPN. MMP-9 showed a superior positive PV to DSPP and OPN. The negative PVs of OPN and MMP-9 were almost identical, and inferior to DSPP. Conclusions: 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. Funding: NIH/NIDCR Grant #K23DE017791-01A1 (KUO); MCGRI Grant #STP00105W005 (KUO); Intramural Research Program, NIH/NIDCR (LWF).