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Giant Cell Tumour of Bone (GCTB) is a rare bone tumour. Locally aggressive and recurrent, it might evolve into pulmonary metastases. Our present work is aimed at investigating the involvement of the epidermal growth factor receptor (ErbB) family and its downstream effectors in the development and recurrence of GCTB. For this purpose, we used a cohort of 32 GCTB patients and we evaluated the clinicohistological features and the expression of RANKL, EGFR, and HER2. The mutation status of KRAS, PI3KCA, and PTEN gene as potential oncogene involved in GCTB was also evaluated. We found a significant correlation between advanced histological stages, overexpression of EGFR/HER2, and tumour recurrence. Moreover, two mutations were found in the PIK3CA gene: a missense mutation, 1634A>C, detected for the first time in GCTB patients, without influencing the stability of the protein, and a frameshift mutation, c.1658_1659delGTinsC, causing the loss of the protein kinase domain. Altogether, these results suggest that overexpression of HER2/EGFR, Campanacci, and histological stages could be used as a novel prognostic marker for GCTB recurrence.

Significance of EGFR/HER2 Expression and PIK3CA Mutations in Giant Cell Tumour of Bone Development