Immunohistochemical analysis of matrix metalloproteinase-1, -3, and -13 in naturally occurring cartilaginous tumors of dogs

Keiichi Kuroki DVM1, John M. Kreeger DVM, PhD2,3, James L. Cook DVM, PhD4, James L. Tomlinson DVM, MVSc5, Gayle C. Johnson DVM, PhD6,7, Lanny W. Pace DVM, PhD8,9, Susan E. Turnquist DVM, PhD10, James R. Turk DVM, PhD11, Jose A. Ramos DVM, PhD12, and Margaret A. Miller DVM, PhD13
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  • 1 Comparative Orthopaedic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 2 Comparative Orthopaedic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 3 Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 4 Comparative Orthopaedic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 5 Comparative Orthopaedic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 6 Veterinary Medical Diagnostic Laboratory College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 7 Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 8 Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 9 Mississippi Veterinary Diagnostic Laboratory, 2531 Northwest St, Jackson, MS 39216.
  • | 10 Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 11 Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 12 Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.
  • | 13 Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.

Abstract

Objective—To determine immunoreactivity of matrix metalloproteinase (MMP)-1, -3, and -13 in cartilaginous tumors of dogs, correlate expression of MMP with histologic grade of tumors and clinical outcome of dogs, and compare MMP immunoreactivity between chondrosarcomas and chondromas.

Sample Population—Formalin-fixed, paraffin-embedded tissues obtained from samples of naturally occurring chondrosarcomas (n = 31) and chondromas (8) of dogs that were submitted to our veterinary medical diagnostic laboratory.

Procedure—Histologic sections from each sample were stained with H&E and monoclonal antibody to MMP-1, -3, and -13 by use of an avidin-peroxidase immunohistochemical technique. For each section, histologic grade (I, II, or III) and immunohistochemical expression (0, 1, 2, or 3) were evaluated. Clinical outcome was obtained from medical records or interviews with referring veterinarians and scored as a good outcome, moderate outcome, or poor outcome. Correlations among variables and differences between chondrosarcomas and chondromas were analyzed.

Results—Samples from chondrosarcomas had significantly higher immunoreactivity of MMP-1 and -13, compared with immunoreactivity in samples from chondromas. In chondrosarcomas, a significant positive correlation (r, 0.386) was found between MMP-1 and -13 immunoreactivities, and a significant negative correlation (r, –0.390) was detected between MMP-3 and -13 immunoreactivities.

Conclusion and Clinical Relevance—A significant increase in expression of collagenases (MMP-1 and - 13) in chondrosarcomas, compared with expression in chondromas, suggests that collagenases may play an important role in tumor progression, and possibly metastasis, in chondrosarcomas of dogs. (Am J Vet Res 2002;63:1285–1291)

Abstract

Objective—To determine immunoreactivity of matrix metalloproteinase (MMP)-1, -3, and -13 in cartilaginous tumors of dogs, correlate expression of MMP with histologic grade of tumors and clinical outcome of dogs, and compare MMP immunoreactivity between chondrosarcomas and chondromas.

Sample Population—Formalin-fixed, paraffin-embedded tissues obtained from samples of naturally occurring chondrosarcomas (n = 31) and chondromas (8) of dogs that were submitted to our veterinary medical diagnostic laboratory.

Procedure—Histologic sections from each sample were stained with H&E and monoclonal antibody to MMP-1, -3, and -13 by use of an avidin-peroxidase immunohistochemical technique. For each section, histologic grade (I, II, or III) and immunohistochemical expression (0, 1, 2, or 3) were evaluated. Clinical outcome was obtained from medical records or interviews with referring veterinarians and scored as a good outcome, moderate outcome, or poor outcome. Correlations among variables and differences between chondrosarcomas and chondromas were analyzed.

Results—Samples from chondrosarcomas had significantly higher immunoreactivity of MMP-1 and -13, compared with immunoreactivity in samples from chondromas. In chondrosarcomas, a significant positive correlation (r, 0.386) was found between MMP-1 and -13 immunoreactivities, and a significant negative correlation (r, –0.390) was detected between MMP-3 and -13 immunoreactivities.

Conclusion and Clinical Relevance—A significant increase in expression of collagenases (MMP-1 and - 13) in chondrosarcomas, compared with expression in chondromas, suggests that collagenases may play an important role in tumor progression, and possibly metastasis, in chondrosarcomas of dogs. (Am J Vet Res 2002;63:1285–1291)