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 Maurice Weinberger, Stephen Warwick Looney, Li Li, Larry W. Fisher

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)286-298
Number of pages13
JournalOncotarget
Volume3
Issue number3
DOIs
StatePublished - Mar 2012

Fingerprint

Osteopontin
Matrix Metalloproteinase 9
Squamous Cell Carcinoma
Recurrence
Integrin-Binding Sialoprotein
Integrins
Proteins
Staining and Labeling
Ligands
dentin sialophosphoprotein
Margins of Excision
Matrix Metalloproteinase 3
Matrix Metalloproteinase 2
Dentin
Matrix Metalloproteinases
Neoplasms
Radiotherapy
Retrospective Studies
Sensitivity and Specificity

Keywords

  • BSP
  • DSPP
  • MMPs, Tumor-free margin
  • OPN
  • Oral cancer

ASJC Scopus subject areas

  • Oncology

Cite this

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. / Ogbureke, Kalu U.E.; Weinberger, Paul Maurice; Looney, Stephen Warwick; Li, Li; Fisher, Larry W.

In: Oncotarget, Vol. 3, No. 3, 03.2012, p. 286-298.

Research output: Contribution to journalArticle

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abstract = "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.",
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