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

Integrins are involved in extracellular matrix interactions and tumor progression, but the comparative clinical relevance of αvβ3, αvβ5, and αvβ6 in osteosarcoma remains unclear.

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.

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.

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.