Comparative clinical and prognostic significance of integrin αvβ3, αvβ5, and αvβ6 in osteosarcoma.

BACKGROUND: Integrins are involved in extracellular matrix interactions and tumor progression, but the comparative clinical relevance of αvβ3, αvβ5, and αvβ6 in osteosarcoma remains unclear. METHODS: This retrospective cohort included 193 patients with histologically confirmed osteosarcoma and available formalin-fixed, paraffin-embedded tumor specimens, evaluable immunohistochemical staining, and follow-up data. Corresponding hematoxylin and eosin-stained sections were reviewed to identify viable osteosarcoma-containing regions. H-score assessment for αvβ3, αvβ5, and αvβ6 was restricted to morphologically identifiable viable osteosarcoma cells, while non-tumoral staining was excluded. Two observers blinded to clinical data independently evaluated staining intensity and the percentage of positive tumor cells. Median H-scores were used for Kaplan-Meier curve visualization, whereas H-scores were modeled continuously in Cox regression analyses. Event-free survival (EFS) and metastasis-free survival (MFS) were analyzed using Kaplan-Meier and Cox models adjusted for age, sex, and tumor necrosis rate. MFS analyses included 183 patients without metastatic disease at baseline. Exploratory combined-expression analyses were also performed. RESULTS: All three integrins showed heterogeneous expression in osteosarcoma tissues. αvβ3 expression was significantly higher in patients who developed metastatic events during follow-up, whereas αvβ5 and αvβ6 were not associated with metastatic events. High αvβ3 expression was associated with poorer EFS (p = 0.003) and MFS (p = 0.001). In multivariable models, continuous αvβ3 H-score remained associated with poorer EFS (HR, 1.011; 95% CI, 1.005-1.017; p < 0.001) and MFS (HR, 1.012; 95% CI, 1.006-1.019; p < 0.001). αvβ5 and αvβ6 were not significantly associated with survival, and combined-expression analyses did not provide clear additional prognostic discrimination. CONCLUSIONS: Among the three αv-containing integrins examined, αvβ3 showed the most consistent association with metastatic events during follow-up and poorer EFS and MFS. Its long-term prognostic relevance and clinical applicability require validation in larger independent cohorts with longer follow-up.