Clinical pathological characteristics correlation of H3F3A gene mutation in giant cell tumor of bone: a study of 96 cases.

Background: Giant cell tumor of bone (GCTB) has been a common primary bone tumor with potential malignancy and local aggressiveness. H3F3A gene mutation has been gradually understood to be related with GCTB occurrence. However, the relationship between different mutation sites and tumor pathological morphology as well as clinical prognosis is still uncertain. This study aimed to investigate the clinical pathological characteristics of GCTB and analyze the potential correlation between H3F3A and GCTB tumor recurrence and prognosis risk.

Methods: A total of 96 cases of GCTB samples diagnosed by two registered pathologists in the Second Hospital of Shanxi Medical University from January 2019 to December 2023 were collected. The clinical and pathological features of the samples were evaluated by pathological hematoxylin and eosin (HE) staining combined with immunohistochemistry (IHC) experiments. H3F3A mutation status was analyzed based on Sanger sequencing. Further, the associations between H3F3A mutation sites and GCTB clinical features, especially recurrence risk, were explored.

Results: Among the 96 GCTB cases, H3F3A was detected to be mutated in 85 cases (88.54%) with the main mutation site defined as H3F3A G34W (76 cases, 89.41%), and other relatively rare mutation sites including G34V, G34L, and Y41H. Of these sites, Y41H mutation was firstly reported in the study. Meanwhile, 15 of the 96 patients encountered recurrence, with clinicopathological features including the Campanacci grading system (which is based on imaging evaluation), tumor soft tissue invasion, P53 expression, and different mutation sites of H3F3A gene associated with tumor recurrence. In particular, compared with the common H3F3A G34W mutation, other relatively rare mutation sites were revealed to be correlated with increased intravascular tumor thrombin and higher tumor cell mitosis, and these patients tended to have a greater risk of recurrence.

Conclusions: Multiple clinicopathological features of GCTB including Campanacci grading system, soft tissue invasion, and H3F3A mutation in rare gene sites were associated with tumor recurrence, and the cases with rare H3F3A mutation sites encountered recurrence more frequently than those with G34W mutation. It is of clinical significance to elucidate in detail the mutation sites of H3F3A by Sanger or high-throughput sequencing analysis.