Expression of Cyclooxygenase-2 in Osteosarcoma of Bone

Abstract

Several studies indicate that cyclooxygenase-2 (COX-2) is overexpressed in human malignancies, where it produces high levels of prostaglandins and contributes to tumor growth. In this study we have analyzed the expression of COX-2 in a series of 48 skeletal osteosarcomas of different subtypes by immunohistochemistry. In addition, we examined the effects of the specific COX-2 inhibitor Celecoxib on the growth of the human osteosarcoma cell line SaOS-2. Immunoreactivity for COX-2 was observed in 39 out of 48 tumors (81.2%), 30 (76.9%) of which showed a moderate or diffuse immunostaining. Considering the group of 42 primary osteosarcomas, COX-2 immunoreactivity was significantly higher in high grade osteosarcomas, where moderate or diffuse expression was detected in 23 out of 32 cases (71.8%), than in low grade osteosarcomas, where moderate or diffuse expression was detected in 2 out of 10 cases (20%) (P = 0.008, Fisher exact test). In addition, low COX-2 expression was always associated with a good response to chemotherapy (5 out of 5 cases), whereas moderate or diffuse COX-2 expression was associated with a good response in 11 out of 20 cases (55%) (P = 0.12, Fisher exact test). In SaOS-2 osteosarcoma cells, which express COX-2, treatment with Celecoxib determined inhibition of cell proliferation and induction of apoptosis. These results indicate that COX-2 is expressed at high levels in high grade osteosarcomas and support the use of COX-2 inhibitors to improve both the tumor response to chemotherapy and the outcome of osteosarcoma patients.

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].…”

“…Numerous studies have shown COX-2 is expressed in osteosarcoma cell lines [16] and clinical specimens obtained from osteosarcomas [4,14]. Recently, Rodriguez et al [18] reported COX-2 expression of lung metastasis tissue correlated with disease-specific survival in patients with metastatic osteosarcoma.…”

Expression of Molecular Markers in the Tumor and Survival Prognosis in Osteosarcoma

“…Chemical method is assumed to be the most suitable for studies of protein expression in tumor tissues, including osteosarcoma tissue [4,5], and for better understanding of some stages in tumor development. The expression of Bax [8,14], Bcl-2 [11], HER-2/neu [7,12], p53 [7,14], VEGF and VEGF-R [6,9,13], and Cox-2 [10,15] proteins attracts special interest of scientists in immunohistochemical studies of bone tumors. The expression of ErbB-2 [12], VEGF [6], and Cox-2 [15] in the primary tumor is associated with poor survival prognosis for osteosarcoma patients.…”

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

“…COX-2 has been shown to be expressed in a variety of adult solid tumors, such as squamous cell, cervical, lung and colon carcinomas (22)(23)(24)(25). 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).…”