Clinicopathological implications of GNAS in Ewing sarcoma.

The objective of the present study was to determine whether guanine nucleotide-binding protein α stimulating (GNAS) gene expression correlates with pathognomonic signs by analyzing the mutations, methylation status and G-protein α subunit (Gsα) expression of GNAS in Ewing sarcoma (ES). Formalin-fixed paraffin-embedded tissue samples from 77 patients with primary ES were obtained in South Korea, Argentina and Brazil, and were studied via methylation chip assay and direct sequencing of the GNAS gene and immunohistochemical analysis of Gsα. The mutation and methylation statuses of the GNAS gene were examined. Immunohistochemical results were measured with respect to proportion and staining intensity. The results revealed that GNAS genes in ES tumor samples were less methylated compared with normal controls. No mutations were detected at exons 8 or 9 of the GNAS locus complex on chromosome 20q13.3, indicating that the pathogenesis of ES was not associated with GNAS mutation. Gsα expression correlated well with the methylation status of the GNAS gene. Notably, high Gsα expression was detected more frequently in samples from living patients than from decedents, although this was not statistically significant (P=0.055). In conclusion, GNAS mutation is not associated with the pathogenesis of ES tumors. This finding may be used to differentiate ES tumors from metastatic bone lesions with morphological similarity to ES tumors. Analysis of the methylation status of the GNAS gene and immunohistochemical Gsα expression suggests that hypermethylated GNAS (low Gsα expression) in ES may be associated with unfavorable progression with a non-significant trend.

Expression of ezrin and metastatic tumor antigen in osteosarcomas of the jaw.

AIMS AND BACKGROUND: Ezrin is a membrane-cytoskeleton linker protein involved in regulation of the growth and metastatic behavior of cancer cells. Metastatic tumor antigen (MTA) is a potential metastasis-associated protein. The objective of this study was to evaluate the expression of ezrin and MTA and their correlation with clinicopathological features in osteosarcomas of the jaw. METHODS: We analyzed ezrin and MTA protein levels by immunohistochemistry in 31 osteosarcomas of the jaw. RESULTS: The mean age at diagnosis was 39 years and half of the patients were male. The mandible (n = 19) was more frequently involved than the maxilla (n = 12). The predominant histological type was chondroblastic (58.1%) and 24 patients (77.4%) were classified as having a high grade of malignancy. Immunoreactivity for ezrin was identified in 6 of 31 cases (19.4%), while 77.4% displayed expression of MTA. All ezrin-positive patients had high-grade tumors. The high-grade tumors (n = 24) had a higher rate of MTA expression (42.9% vs 87.5%). Expression of ezrin and MTA was not significantly different according to age, sex, tumor site, histological type, and tumor ploidy. Follow-up information was available for 13 patients, with a mean follow-up time of 26.7 months (range, 6-48 months). At the time of last follow-up, 5 (38.5%) patients had died of disease and 8 patients (61.5%) were alive with no evidence of disease. Expression of ezrin and MTA was not significantly different according to the follow-up data. CONCLUSIONS: In our study, high-grade tumors had a higher rate of ezrin and MTA expression. This expression pattern indicates that ezrin and MTA positivity can be additional prognostic markers in osteosarcoma of the jaw.

Osteoid osteoma of the calcaneus: percutaneous radiofrequency ablation.

Osteoid osteoma of the foot can pose particular problems in diagnosis, especially when positioned in a juxta-articular location. It can cause reactive synovitis and simulate arthritis without periostitis. An atypical presentation may delay diagnosis and thus delay treatment. Different modes of treatment have been described including medical management with nonsteroidal, antiinflammatory drugs, and open surgical resection with intralesional, marginal, or wide surgical margins. In recent years, several computed tomography-guided percutaneous techniques have been used to achieve ablation of the nidus with minimal tissue invasion. We report a case of a 39-year-old man with an 8-month history of persistent foot pain who underwent percutaneous radiofrequency ablation of an osteoid osteoma involving the calcaneus. The patient related an immediate relief of pain and had no recurrence of symptoms or the lesion at 3-year follow-up.