Analysis of angiogenic factors and cyclooxygenase-2 expression in cartilaginous tumors – clinical and histological correlation

Abstract

OBJECTIVES:To study the role of angiogenesis and cyclooxygenase-2 expression in cartilaginous tumors and correlate these factors with prognosis.INTRODUCTION:For chondrosarcoma, the histological grade is the current standard for predicting tumor outcome. However, a low-grade chondrosarcoma can follow an aggressive course—as monitored by sequential imaging techniques—even when it is histologically indistinguishable from an enchondroma. Therefore, additional tools are needed to help identify the biological potential of these tumors. The degree of angiogenesis that is induced by the tumor could assist in this task. Angiogenesis can be quantified by measuring the expression of vascular endothelial growth factor and CD34, and cyclooxygenase-2 can induce angiogenesis by stimulating the production of pro-angiogenic factors.METHODS:In total, 21 enchondromas and 58 conventional chondrosarcomas were studied by examining the clinical and histopathological findings in conjunction with the immunostaining markers of angiogenesis and cyclooxygenase-2 expression.RESULTS:The significant variables that were associated with poor outcome were 1) higher-grade chondrosarcomas, 2) tumors that developed in flat bones, and 3) over-expression of CD34 (with a median count that was higher than 5.9 vessels in 5 high power fields). Moreover, CD34 expression (measured using the Chalkley method) revealed significantly higher microvessel density in flat bone chondrosarcomas.DISCUSSION:Previous studies have shown a positive correlation between Chalkley microvessel density and histological grade; however, in our sample, we found that the former is predictive of the outcome. Chondrosarcomas in flat bones have been shown to correlate with a poor prognosis. We also found that CD34 microvessel density values were significantly higher in flat-bone chondrosarcomas. This could explain—at least in part—the more aggressive biological course that is taken by these tumors.CONCLUSIONS:These results provide evidence that CD34 microvessel density in chondrosarcomas can be helpful in predicting patient outcome and may add to our understanding of chondrosarcoma pathogenesis.

Biomarkers of Osteosarcoma, Chondrosarcoma, and Ewing Sarcoma

“…Cintra et al (2011) investigated the role of COX-2 expression and angiogenetic factors in chondrosarcoma progression. The authors observed that a high COX-2 expression adversely affects patient survival and a positive correlation between CD34 and COX-2 expression, which confirms the relationship between COX-2 and angiogenesis, suggesting a possible role for this marker in patient prognosis (Cintra et al, 2011).…”

Identification of novel biomarker candidates for immunohistochemical diagnosis to distinguish low‐grade chondrosarcoma from enchondroma

“…Chondrosarcoma is the third most common primary bone cancer . Based on cellularity, nuclear atypia, and pleomorphism, chondrosarcoma is histologically classified into three grades including low grade (grade 1), intermediate grade (grade 2), and high grade (grade 3) . Wide surgical resection is the most common treatment choice for chondrosarcoma .…”

Radiologic differentiation of enchondromas, atypical cartilaginous tumors, and high‐grade chondrosarcomas—Improving tumor‐specific treatment: A paradigm in transit?

“…[12][13][14][15] Also, expansion in small bones, a diaphyseal location, superficial scalloping, septonodular enhancement on MRI, a size less than 5 cm in long bones, and even some increase in size are consistent with the diagnosis of enchondroma. 14,16,[18][19][20][21][22][23][24][25] Fortunately, the clinically more relevant differentiation between ACTs and grade 2 or higher CSs is more reliable on imaging (and histology). 14,16,[18][19][20][21][22][23][24][25] Fortunately, the clinically more relevant differentiation between ACTs and grade 2 or higher CSs is more reliable on imaging (and histology).…”

“…27 MRI is the method of choice for displaying not only these radiographic features (with the exception of calcifications) but also features of high-grade CS, such as abundant (>50%) mucoid (which has a high signal intensity on fluid-sensitive MRI sequences), cortical thickening (also well seen on radiographs and computed tomography), cortical destruction, soft-tissue extension, perilesional inflammatory reactions in bone and soft tissue, and periostitis. 20,21,23 With these parameters, the diagnostic accuracy of MRI is greater than 90%. 20,21,23 With these parameters, the diagnostic accuracy of MRI is greater than 90%.…”