COX-2 Expression Correlates With Survival in Patients With Osteosarcoma Lung Metastases

Abstract

SummaryThe purpose of this study was to determine whether a correlation exists between tumor cyclooxygenase (COX)-2 expression and disease-specific survival in patients with osteosarcoma lung metastases. Thirty-six patients diagnosed with osteosarcoma lung metastases between the years 1990 and 2001 were included in this retrospective study. The majority of the patients (72%) presented newly -diagnosed osteosarcoma lung metastases whereas the remaining patients (28%) presented recurrent disease. Clinicopathologic parameters were obtained from patients' clinical records. Tissue samples were obtained at the time of resection of the lung metastases and stained for COX-2 using immunohistochemistry. Samples were graded according to the intensity of COX-2 staining (grade 0: negative, grade 1: very weak, grade 2: weak, grade 3: moderate, and grade 4: strong). COX-2 staining was correlated with disease-specific survival and clinicopathologic parameters using the Jonckheere-Terpstra and the Kruskal-Wallis tests. All patients with grade 3 or 4 COX-2 expression died of osteosarcoma lung metastases. Ten percent of patients with grade 2 COX-2 expression and 29% of patients with grade 1 expression were alive and free of disease at the last follow-up. By contrast, 60% of the patients with grade 0 COX-2 expression were alive and free of disease at the last follow-up. No association between COX-2 expression and clinicopathologic parameters was found. However, COX-2 expression correlated inversely with disease-specific survival in patients with osteosarcoma lung metastases. Our data indicate that COX-2 expression in metastatic osteosarcoma may have prognostic significance. KeywordsCOX-2; osteosarcoma; lung metastases Soft tissue and bone sarcomas comprise nearly 13% of all cancers in childhood. Approximately 1500 new cases of pediatric sarcoma are diagnosed each year in the United States.1 For osteosarcoma, the most common primary tumor site is the metaphysis of long bones, and the most common site of metastatic involvement is the lungs. Patients with Reprints: Nidra I. Rodriguez, MD, Children

Cyclooxygenase-2 Overexpression Predicts Poor Survival in Patients with High-grade Extremity Osteosarcoma: A Pilot Study

“…This discrepancy may be attributable partly to differences in the sensitivity of the anti-COX-2 antibody used, the cutoff value, or various aspects of treatments such as surgical margin and chemotherapy protocols. We observed a higher frequency of cases with COX-2 positivity than reported in other studies (92% in our study versus 67% to 86%) [4,14,18], leading us to set a higher cutoff value. The study of pediatric osteosarcomas did not describe the demographic data, including the grade of osteosarcoma, resectability of the tumors, or therapeutic methods, including surgical margin and chemotherapy protocols [4].…”

“…The study of pediatric osteosarcomas did not describe the demographic data, including the grade of osteosarcoma, resectability of the tumors, or therapeutic methods, including surgical margin and chemotherapy protocols [4]. Another possibility is the heterogeneity of each patient group contributed to the inaccurate results in the studies [4,14,18]. Several prognostic risk factors have been proposed, including tumor size, site, age, history of symptoms, treatment delay, margin, and response to chemotherapy [1,3].…”

“…Recently, Rodriguez et al [18] reported COX-2 expression of lung metastasis tissue correlated with disease-specific survival in patients with metastatic osteosarcoma. However, there is little evidence COX-2 overexpression in primary tumors correlates with the clinical outcome of patients with osteosarcoma after surgical treatment combined with neoadjuvant and adjuvant chemotherapy.…”

Cyclooxygenase-2 expression is not associated with clinical outcome in synovial sarcoma

“…COX-2 has also been shown to be expressed in a variety of sarcomas, including rhabdomyosarcoma, osteosarcoma, Ewing's sarcoma and chondrosarcoma (26)(27)(28) tumor types (29)(30)(31)(32)(33)(34)(35). Although overexpression of COX-2 has been associated with poor prognosis in chondrosarcoma (36), esophageal squamous cell carcinoma (37) and osteosarcoma (38,39), no relationship between COX-2 expression and patient outcomes has been identified in either rhabdomyosarcoma or most adult soft tissue sarcomas (40).…”

Reduced expression and prognostic implication of inhibitor of growth 4 in human osteosarcoma

“…Osteosarcoma has an overwhelming tendency for invasion and early metastasis (2). Although treatment with surgery and neoadjuvant chemotherapy appears to cure 60-70% of cases (3), the 5-year survival rate for patients with recurrent and metastatic osteosarcoma is only 20% (4,5). Research investigating the mechanism of osteosarcoma development has primarily focused on chromosomal abnormalities, genetic alterations of tumor suppressor genes, activation of oncogenes and dysregulation of major signaling pathways.…”