title: Gene expression profiling identifies p63 as a diagnostic marker for giant cell tumor of the bone.
abstract: Giant cell tumor of the bone (GCTOB) is a primary bone tumor that occurs mainly in young adults and is capable of locally aggressive growth. Its histologic appearance can resemble a number of benign and malignant tumors but no useful diagnostic marker is known currently. To identify diagnostic markers for this tumor, global gene expression profiling using cDNA microarray was performed on 6 fresh-frozen GCTOB, 3 aneurysmal bone cysts, 4 fibrous dysplasias and 12 giant cell tumors of tendon sheath/diffuse-type giant cell tumors. Unsupervised hierarchical clustering separated the tumors based on their histopathologic types, and significance analysis of microarray identified several genes including TP73L (encoding the p63 protein) that are significantly highly expressed in GCTOB relative to these other tumors. The diagnostic utility of p63 was subsequently confirmed using anti-p63 antibody on a series of 26 GCTOB, 25 aneurysmal bone cysts, 15 chondroblastomas, 13 giant cell reparative granulomas, 13 chondromyxoid fibromas, 4 brown tumors, 4 fibrous dysplasias, 53 giant cell tumors of tendon sheath/diffuse-type giant cell tumors and 385 additional mesenchymal tumors in tissue microarrays. Strong p63 nuclear staining was present in 18 of 26 (69%) GCTOB, 3 of 15 (20%) chondroblastomas and in 1 of 25 (4%) aneurysmal bone cysts while none of the other tumors commonly considered in the differential diagnosis of GCTOB showed any detectable p63 staining. Strong p63 staining is rare in bone and soft-tissue tumors in general. In contrast to the pattern of p63 staining, the majority of the chondroblastomas (70%) demonstrated S-100 immunoreactivity while only a minority of the GCTOB (8%) was immunoreactive for S-100. These findings altogether show that p63 can be used as a diagnostic marker to aid the clinical diagnosis of GCTOB.
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.forename: Inigo
authors.initials: I
authors.lastname: Espinosa
authors.forename: Kristin C
authors.initials: KC
authors.lastname: Jensen
authors.forename: Subbaya
authors.initials: S
authors.lastname: Subramanian
authors.forename: Shirley X
authors.initials: SX
authors.lastname: Zhu
authors.forename: Sushama
authors.initials: S
authors.lastname: Varma
authors.forename: Kelli D
authors.initials: KD
authors.lastname: Montgomery
authors.forename: Torsten O
authors.initials: TO
authors.lastname: Nielsen
authors.forename: Matt
authors.initials: M
authors.lastname: van de Rijn
authors.forename: Robert B
authors.initials: RB
authors.lastname: West
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D017824:Bone Cysts, Aneurysmal / Q000473:pathology; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D018212:Giant Cell Tumor of Bone / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012509:Sarcoma / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C081876:CKAP4 protein, human; D008565:Membrane Proteins