Giant Cell Tumors: Inquiry Into Immunohistochemical Expression of CD117 (c-Kit), Microphthalmia Transcription Factor, Tartrate-Resistant Acid Phosphatase, and HAM-56

Abstract

Osteoclast-like giant cells (GCs) in giant cell tumors (GCTs) are thought to derive from a monocyte-macrophage lineage. Microphthalmia transcription factor (MITF) is necessary for osteoclast gene expression and tartrate-resistant acid phosphatase (TRAP) activation; c-Kit plays a role in regulation of MITF. To gain insight into the differentiation of GCTs of bone (GCTBs) and GCTs tendon sheath (GCTTSs) by investigating immunohistochemical staining for c-Kit, MITF, TRAP, and HAM-56 in the GCs and stroma. Immunoreactivity for CD117 (c-Kit), MITF, TRAP, and HAM-56 was studied in 35 GCTBs, 15 GCTTSs, and 5 foreign-body GC controls. Across tumors, MITF and TRAP but not c-Kit were generally expressed in GCs; TRAP was variably expressed in stromal cells. The MITF was expressed more consistently in stromal cells of GCTTSs than GCTBs (P < .001). The GCTBs showed more intense MITF stromal (P < .001) and TRAP GC staining (P = .04) than GCTTSs. HAM-56 staining by stromal cells was associated with MITF stromal staining (r2 = 0.6, P < .001). Results suggest that MITF and TRAP are expressed during osteoclast differentiation and that a proportion of mononuclear cells in GCTs express the macrophage marker HAM-56. Both GCTBs and GCTTSs show similar patterns of immunohistochemical expression.