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Cyclooxygenase-2 (COX-2) overexpression is associated with a poor prognosis in chondrosarcomas

12 th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006. Cyclooxygenase-2 (COX-2) overexpression is associated with a poor prognosis in chondrosarcomas. Makoto Endo, 1 Tadaki Matsumura, 2 Umio Yamaguchi, 1 Fumihiko Nakatani, 1 Akira Kawai, 1 Hirokazu Chuman, 1

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Cyclooxygenase-2 (COX-2) overexpression is associated with a poor prognosis in chondrosarcomas

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  1. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Cyclooxygenase-2 (COX-2) overexpressionis associated with a poor prognosis in chondrosarcomas Makoto Endo,1 Tadaki Matsumura,2 Umio Yamaguchi,1 Fumihiko Nakatani,1 Akira Kawai,1 Hirokazu Chuman,1 Yasuo Beppu,1 Tadashi Hasegawa2 1 Division of Orthopaedic Oncology, National Cancer Center Hospital, Tokyo, Japan 2 Department of Clinical Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan

  2. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Background Chondrosarcoma The second most common malignant bone tumor A broad array of presentations The histologic grade is the standard for predicting the outcome

  3. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Grading ofchondrosarcomas The histologic grading system is separated intothree grades Based on 1. cellularity 2. nuclear atypia 3. pleomorphism Fletcher CDM, et al (eds): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone, 2002.

  4. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Grade 1 In some borderline cases, exact histologic grading is difficult using only routine histopathologic examinations Grade 2 Grade 3

  5. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Cyclooxygenase-2 (COX-2) An isoform of COX A key enzyme that catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid COX-2-derived PGsplay an important role in carcinogenesis 1. induceangiogenesis 2. inhibitapoptosisand immune surveillance 3. increase invasion and metastatic potential

  6. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Purpose To investigate the expression profile of COX-2 using immunohistochemical staining in formalin-fixed, paraffin-embedded chondrosarcoma specimens To confirm whether COX-2 expression is associated with prognosis

  7. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Materials & Methods 74 patients Sex: men, 37; women, 37 Age: 14 - 81 y/o (median, 50 y/o) Size: 2.7 - 32 cm (median, 8.0 cm)

  8. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Location: Axial skeleton, 47 (pelvis, 20; rib, 19; vertebra, 4; scapula, 3; skull base, 1) Long bones, 27 (femur, 10; humerus, 5; tibia, 5; fibula, 2; ulna, 1; others, 4)

  9. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Immunohistochemical analysis of COX-2 A monoclonal anti-COX-2 antibody (clone CX-294; 1:100; DakoCytomation) Definition of overexpression: More than 10% of the tumor cells stained

  10. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 • COX-2 staining in the chondrosarcomas was • consistently observed in atypical chondrocytes • with a strong and cytoplasmic pattern

  11. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 • ＜10% of cells stained • = Negative • ≧10% of cells stained • = Positive

  12. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Results (74 cases) Histologic grade Grade 1: 39 Grade 2: 32 Grade 3: 3 • COX-2 overexpression • Positive: 16 (22%) • Negative: 58 (78%)

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  15. 12th CTOS Annual Meeting in Venice, Italy Cumulative Disease-specific Survival (%) 100 COX-2 overexpression (-) 90 80 70 60 50 COX-2 overexpression (+) 40 30 20 10 0 0 50 100 150 200 Months

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  17. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Discussion The first immunohistochemical evidence that COX-2 overexpression is significantly associated with decreased survival

  18. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Discussion In the multivariate analysis, the only independent risk factor for a poor outcome was a high histologic grade. COX-2 overexpression was significantly associated with the histologic grade.

  19. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Discussion COX-2 overexpression can be definitively evaluated based on the proportion of stained tumor cells, enabling the subjectivity of interpretations to be minimized.

  20. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Conclusion COX-2 overexpression in chondro- sarcomas is a useful predictor of patient outcome that is strongly associated with histologic grade.

  21. 12th CTOS Annual Meeting in Venice, Italy 2-4, November, 2006 Acknowledgements • Pediatric oncology • Ako Hosono • Pathology • Kunihiko Seki • Secretarial assistance • Yuriko Kawaguchi Orthopaedic oncology Yuki Morimoto Yoshiyuki Suehara Eisuke Kobayashi Ken Takeda

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