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

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 proangiogenic 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.

Proximal-type epithelioid sarcoma in pubis. Case report and review of the literature.

BACKGROUND: The "proximal-type" epithelioid sarcoma (PES) is a rare variant of conventional epithelioid sarcoma. It has been described in older patients in the proximal portion of the extremities with a predilection for the pelvis and perineum. It is clinically more aggressive, showing a higher incidence of recurrence, metastasis, resistance to chemotherapy and a higher mortality. We report the case of a patient with a PES of the pubic region and we review the previous literature. CLINICAL CASE: We report the case of a 57-year-old female with a painless, progressively growing mass in the region of the pubis. We performed surgical resection of the lesion with clear margins and histological and immunohistochemical study allowed the definitive diagnosis of PES. After 4 disease-free years, the patient had a tumor recurrence at the same location. We performed en bloc resection of the lesion and immunohistochemical study confirmed the recurrence of PES. The patient refused adjuvant therapy. Today, after 4 years of follow-up, the patient remains asymptomatic and without evidence of recurrence or distant disease. CONCLUSIONS: Diagnosis of PES is complex because histological findings may be confused with multiple tumors; therefore, immunohistochemical study is definitive. PES shows positivity for epithelial markers (cytokeratin and EMA), mesenchymal markers (vimentin) as well as CD34. According to what has been reported in the literature, surgical treatment with free margins is indicated, with adjuvant therapies when the risk of recurrence is high.

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

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 proangiogenic 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.

Glial fibrillary acidic protein in tumor types with cartilaginous differentiation.

Glial fibrillary acidic protein (GFAP) is a member of the intermediary filament protein family. It is an important component of astrocytes and a known diagnostic marker of glial differentiation. GFAP is expressed in other neural tumors and pleomorphic adenoma and, less frequently, in cartilage tumors, chordomas, and soft tissue myoepitheliomas. The aim of this study was to evaluate the role of GFAP and its reliability in nonglial tumors as an immunohistochemical marker. We evaluated GFAP gene and protein expression using Q-PCR and immunohistochemistry, respectively, in 81 and 387 cases of soft tissue, bone tumors, and salivary pleomorphic adenomas. Immunohistochemistry staining for GFAP was observed in all osteosarcomas (8 cases), all pleomorphic adenomas (7 cases), in 5 of 6 soft tissue myoepitheliomas, and in 21 of 76 chondrosarcomas. By Q-PCR, GFAP was highly expressed in pleomorphic adenomas and, to a lesser extent, chondrosarcomas, soft tissue myoepitheliomas, and chondroblastic osteosarcomas. The results that we obtained by immunohistochemistry and Q-PCR were well correlated. GFAP is a potential marker for tumors with cartilaginous differentiation, supported by evidence that GFAP is expressed in certain cases of myoepithelial tumors by immunohistochemistry, including soft tissue myoepitheliomas, which are related to cartilaginous differentiation. These findings contribute significantly to the diagnosis of soft tissue myoepitheliomas with cartilaginous differentiation and chondroblastic osteosarcoma in mesenchymal tumors.

RANKL expression in a case of follicular lymphoma.

The TNF-family molecule, RANKL, is a key regulator of bone remodeling and essential for the development and activation of osteoclasis. Bone involvement signals diesease activity in non-Hodgkin's lymphoma and influences the progenesis. The molecular mechanism and soluble factors involved in osteoclastic activation in haematological malignancies remain unclear except for Multiple Myeloma and Adult T-cell Leukemia. The aim of this paper is to report the first case of Follicular Lymphoma with bone involvement displaying an aberrant expression of RANKL in malignant cells. The detection of RANKL in Follicullar Lymphoma may help to prevent bone lesion in patients by determining an appropriate treatment.

Estrogen receptor expression in giant cell tumors of the bone.

Giant cell tumors (GCTs) of the bone are primary skeletal neoplasms that behave intermediately between a true benign and an overtly malignant neoplasm. For two decades, controversial reports have found estrogen receptor (ER) expression in isolated cells or small numbers of samples from these tumors. In this report, we studied by immunohistochemistry 88 cases of GCTs and found that 51% of the samples expressed ER. Furthermore, we found that a subset of seven samples analyzed for ER expression by western blot was positive. To address whether the ER expressed in these samples could be functional, isolated cells were exposed to beta-estradiol and growth curves were generated. Exposure of cells to beta-estradiol induced a small but significant growth in the cells. These results strongly support that GCTs of the bone express functional ERs.