High-Expression of PTEN and an Absence of PCNA in Osteoclast-Like Multinucleated Giant Cells of Giant Cell Tumors in Bone

Abstract

Giant cell tumors (GCTs) found in bone are so named for the conspicuous presence of numerous osteoclast-like multinucleated giant cells (OLMGCs). Although GCT studies have revealed that the OLMGCs are the cells responsible for tumor formation, these cells continue to receive a good deal of research attention. The tumor -suppressor gene, PTEN, is known to be involved in various malignancies. Recently, however, PTEN has been reported to be important for neuron enlargement and cardiomyocyte hypertrophy. Given the role of PTEN in both carcinomas as well as cell hypertrophy, we sought to elucidate the relationship between PTEN and OLMGCs. In this study, we confirmed the existence of PTEN in GCTs in bone using PCR. In particular, exons-3,4 and 5 of the PTEN gene was detected. Exons-3,4,5 of PTEN gene were found by PCR in all of 8 cases. Single cells microdissection was used to isolate OLMGCs from GCTs and verify the existence of the PTEN gene in the osteoclast-like multinucleated giant cells through PCR amplication of PTEN exon-3. Exon-3 of PTEN were detected by PCR in 5 of the 10 microdissected samples. PTEN mRNA expression was detected by in situ hybridization and the expressions of PTEN protein and proliferating cell nuclear antigen (PCNA) in GCTs were detected by immunohistochemistry. High expression levels of PTEN mRNA was detected only in OLMGCs in 23 of 27 GCT cases. Likewise,high expression of PTEN protein was also found only in OLMGCs in 21 of the 27 GCT cases and the giant cells did not express PCNA. In contrast, the neoplastic stromal cells with high PCNA labeling were almost always PTEN-negative by immunohistochemical staining. These results suggested that high-expression of PTEN in OLMGCs may involve in the formation size of GCTs.