AbstractBackgroundC‐erbB‐2 is postulated as a prognostic biological marker for osteosarcoma (OST). We investigated c‐erbB‐2 expression status in osteosarcomas and its prognostic significance.ProcedureArchival pre‐treatment tumor biopsies of 79 cases were stained by immunohistochemical (IHC) methods with CB11 antibody for cell‐membrane specific c‐erbB‐2 expression. Relation with different variables was examined and survival rates were calculated.ResultsMedian age was 13 years (7–17). Distant metastases were detected in 8 (10.1%) cases at initial diagnosis. 36/79 (45.6%) patients had positive c‐erbB‐2 staining by IHC. There was no significant difference between c‐erbB‐2 expression and presence of distant metastases at initial diagnosis or during follow‐up, gender, age groups, tumor size, tumor sites, serum alkaline phosphatase, and lactate dehydrogenase levels. At a median follow‐up of 67.4 months (9.2–246.1), 36 cases died, 20 were alive, and 23 abandoned treatment. For 58 cases without initial metastases who underwent definitive surgery, 5‐year event‐free (EFS) and overall survival (OS) rates were 50% and 62.1% in cases negative for c‐erbB‐2 expression, and 22.4% and 32.3% in cases positive for c‐erbB‐2 expression, respectively (EFS,P = 0.044; OS,P = 0.029). Five‐year EFS and OS rates were significantly higher in cases with a tumor size <10 cm. Cox regression analyses revealed that only size persisted as a prognostic factor for EFS. C‐erbB‐2 expression status didn't appear as an independent prognostic factor.ConclusionsOverexpression of c‐erbB‐2 in OST was not correlated with metastatic potential. No independent prognostic significance was detected. The results do not support directed therapies for c‐erbB‐2 in OST. Pediatr Blood Cancer 2008;51:222–227. © 2008 Wiley‐Liss, Inc.