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.

Factors Affecting the Recurrence of Giant Cell Tumor of Bone After Surgery: A Clinicopathological Study of 80 Cases from a Single Center

“…When the number of CD147-positive cells was ≤5%, the tissue was considered negative; 6-25%, weak; 26-50%, moderate; and ≥51%, strong [16]. When the number of nuclei positively stained for p63 or mutant p53 was >10%, the tissue was considered positive, otherwise the tissue was considered negative [17]. …”

Cytoplasmic p63 immunohistochemistry is a useful marker for muscle differentiation: an immunohistochemical and immunoelectron microscopic study

“…[2][3][4] p63 immunostaining is also used to support a diagnosis of squamous cell carcinoma in various sites, including the head and neck, lung, 5 uterine cervix, and anus, 6 as well as metaplastic carcinoma of the breast, 7 urothelial carcinoma, sarcomatoid carcinoma, 8 and giant cell tumor of bone. 9,10 Recently, it was found that all p53 family members are involved in regulating muscle differentiation through the retinoblastoma (RB) protein.…”

Differentially expressed genes in giant cell tumor of bone

“…They can be locally aggressive and destructive with rapid growth leading to thinning and rupture of the cortical bone with invasion of adjacent soft tissues, but without invading and ulcerating the skin and subcutaneous tissue [3,4]. Generally, GCTBs most frequently occur in young adults between 20 and 40 years of age, with a slight predominance in females.…”

“…Generally, GCTBs most frequently occur in young adults between 20 and 40 years of age, with a slight predominance in females. They affect mainly the ends of long bones, and frequently occur in the distal end of the femur and the proximal end of the tibia [5][6][7][8].…”