Genetic Analysis of Giant Cell Lesions of the Maxillofacial and Axial/Appendicular Skeleton

Publication date: Available online 26 July 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Zachary S. Peacock, Joseph H. Schwab, William C. Faquin, Francis Hornicek, Yair Benita, David H. Ebb, Leonard B. Kaban
PurposeTo compare genetic and protein expression of giant cell lesions (GCL) of the maxillofacial (MF) and axial/appendicular (AA) skeletons. We hypothesized that when grouped according to biologic behavior and not simply location, MF and AA GCLs exhibit common genetic characteristics.MethodsThis was a prospective and retrospective study of patients with GCLs treated at Massachusetts General Hospital from 1993 to 2008. In a preliminary prospective study, fresh tissue from 6 aggressive(A) tumors each from the MF and AA skeletons (n=12 tumors) was obtained. RNA was extracted and amplified from giant cells(GCs) and stromal cells first separated by Laser capture micro-dissection. Genes highly expressed by GCs and stroma at both locations were determined by an Affymetrix GeneChip® analysis. As confirmation, a tissue microarray(TMA) was created retrospectively from representative tissue of preserved pathologic specimens to assess protein expression of the commonly expressed genes from the prospective study. Quantification of immunohistochemical staining of MF and AA lesions was performed with Aperio® image analysis to determine if immunoreactivity was predictive for aggressive or non-aggressive behavior.ResultsFive highly ranked genes were found commonly in GCs and stroma at each location: matrix metalloproteinase-9 (MMP9), cathepsin K (CTSK) T-cell immune regulator-1 (TCIRG1), C-type lectin domain family-11 (Clec11A) and zinc finger protein-836 (ZNF836). MF (n=40; 32A) and AA (n=48 28A) paraffin-embedded tumors were included in the TMA. The proteins CTSK, MMP9, and TCIRG1 were confirmed to have abundant expression within both MF and AA lesions. Only staining levels for TCIRG1 within the GCs predicted clinical behavior in MF lesions.ConclusionMMP9, CTSK and TCIRG1 are commonly expressed by GCLs of the MF and AA skeleton. This supports the hypothesis that these lesions are similar, but at different locations. TCIRG1 has not been previously associated with GCLs and may be a potential target for molecular diagnosis and/or therapy.



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