Induction chemotherapy for bone sarcoma in adults: correlation of results with erbB-4 expression. Tumor response to preoperative chemotherapy is an important prognostic factor for localized, operable extremity osteosarcoma. Other clinical variables include tumor size and location, age and sex, and serum enzymes. Advances in molecular oncology yielded a second group of factors such as multidrug resistance status, loss of heterozygosity of RB gene, and HER2/erbB-2 expression. The aim of this study was to investigate the expression and the prognostic value of the newly described erbB-4 receptor in specimens from adults with bone sarcomas treated by pre- and postoperative chemotherapy. Thirty-three patients with non-metastatic bone sarcoma have been treated by two doxorubicin-based induction chemotherapy regimen, followed by limb sparing surgery and tailored adjuvant chemotherapy. Pre-chemotherapy tissue specimens were investigated for the expression of erbB-4 receptor and post-induction specimens were assessed for pathological response. The clinical response rates were 32-36%. The degree of induced necrosis was correlated with the disease-free survival (DFS). Patients achieving >/=90% necrosis had an improved DFS over patients with poor histological response. ErbB-4 expression was significantly associated with poor histologic response and shorter DFS. ErbB-4 expression may be used for prognostication of adults with bone sarcomas.