Effect of ALDH1A1 and CD44 on Survival and Disease Recurrence in Patients With Osteosarcoma.

PURPOSE: Emerging evidence suggests that osteosarcoma stem cells (OSCs) may be responsible for tumor initiation propagation, recurrence, and resistance to therapy. We set out to evaluate the relationship between the abundance of ALDH1A1 and CD44-positive cells in biopsy and resection samples on disease recurrence and overall survival.

METHODS: A retrospective review of 20 patients, including biopsy and resection samples, was performed at a comprehensive cancer center. Additionally, we queried the publicly available TARGET dataset of osteosarcoma patients.

RESULTS: Neither the percentages of ALDH1A1-positive cells nor CD44-positive cells were significantly associated with overall mortality or disease recurrence in either biopsy or resection samples. Unlike our institutional data, overall survival was significantly correlated to higher ALDH1A1 expression in the TARGET dataset both in univariate and age-adjusted analyses.

CONCLUSIONS: ADLH1 and CD44, potential markers of OSCs, were not found to be reliable clinical immunohistochemical prognostic markers for osteosarcoma patient survival, specifically disease-free survival. Osteosarcoma patients with high ALDH1A1 RNA expression showed improved overall survival in examining a national genomic database of osteosarcoma patients but again no association with disease-free survival. The potential of CD44 and ALDH1A1 as cellular-specific prognostic markers of survival, and as possible molecular targets, may be limited in osteosarcoma.