Oncotarget

Research Papers:

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

Kalu U. E. Ogbureke _, Paul M. Weinberger, Stephen W. Lonney, Li Li and Larry W. Fisher

PDF  |  HTML  |  How to cite

Oncotarget. 2012; 3:286-298. https://doi.org/10.18632/oncotarget.373

Metrics: PDF 3214 views  |   HTML 3380 views  |   ?  


Abstract

Kalu U.E. Ogbureke1,2,3, Paul M. Weinberger2, Stephen W. Looney1,3, Li Li4, Larry W. Fisher4

1 College of Dental Medicine, Georgia Health Sciences University, 1120 15th Street, Augusta, GA

2 Medical College of Georgia, Georgia Health Sciences University, 1120 15th Street, Augusta, GA

3 College of Graduate Studies, Georgia Health Sciences University, 1120 15th Street, Augusta, GA

4 Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, NIH, 30 Convent Drive, Building 30, Room 228, Bethesda, MD

Received: January 23, 2012; Accepted: March 2, 2012; Published: March 11, 2012;

Keywords: Oral Cancer, DSPP, BSP, OPN, MMPs, Tumor-Free Margin

Correspondence:

Kalu U.E. Ogbureke,

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” (< 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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 373