title: Distribution and prognostic significance of human telomerase reverse transcriptase (hTERT) expression in giant-cell tumor of bone.
abstract: Giant-cell tumor of bone is considered a benign, locally aggressive and rarely metastasizing neoplasm of bone. Specific microscopic or radiographic findings that reliably predict behavior have remained elusive. However, recent evidence suggests that activity of the telomerase enzyme complex correlates with recurrence in giant-cell tumor, although the subset of cells with telomerase activity in these heterogeneous tumors has not been defined. In the present study, we investigated whether immunostaining for human telomerase reverse transcriptase, a component of the telomerase complex, correlates with outcome in giant-cell tumor and the distribution of telomerase reverse transcriptase staining in these tumors. We analyzed 58 cases of giant-cell tumor for the presence and pattern of telomerase reverse transcriptase immunostaining, presence of soft tissue involvement and the type of initial surgery, and correlated these findings with recurrence-free survival and metastasis-free survival. Specific staining with telomerase reverse transcriptase was present in 20 out of 58 tumors (35%) in the nuclei of mononuclear cells and, occasionally, osteoclast-like giant cells. Furthermore, positive telomerase reverse transcriptase immunohistochemistry correlated with recurrence-free survival (P=0.02), whereas the presence of soft tissue extension (P=0.3) and the type of initial surgery (P=0.2) did not. Only soft-tissue extension significantly correlated with metastasis-free survival (P=0.003). Therefore, telomerase reverse transcriptase expression may predict recurrence in giant-cell tumor insofar as positive immunostaining correlates with shorter recurrence-free survival and may be a useful prognostic marker to stratify patients to more aggressive treatment protocols.
authors.affiliation: Department of Pathology, University of California, 1600 Divisadero Drive B220, San Francisco, CA 94115-1656, USA. andho@itsa.ucsf.edu
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Horvai
authors.forename: Miranda J
authors.initials: MJ
authors.lastname: Kramer
authors.forename: Joaquin J
authors.initials: JJ
authors.lastname: Garcia
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Donnell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011379:Prognosis; D019098:Telomerase / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C509186:TERT protein, human; D019098:Telomerase