ErbB-4 expression in limb soft-tissue sarcoma: correlation with the results of neoadjuvant chemotherapy.

ErbB-4 is a recently described growth factor receptor. Relatively little is known about its expression in human tumours. In this study, we assessed the possible role of erbB-4 as a tissue marker for soft-tissue sarcomas (STS) and its correlation with the response to chemotherapy. The histological specimen of 29 patients with STS of a limb who had received preoperative doxorubicin (ADR)-based chemotherapy were studied for the degree of necrosis and the expression of erbB-4 (by an avidin-biotin-peroxidase technique). ErbB-4 expression in the preoperative tissue samples was compared with the expression in the postchemotherapy resected tumour. The true objective response rate to preoperative chemotherapy was 34%. Wide resection of the tumour was done in 12 patients, marginal in 14, amputation in 2 and no surgery in 1. The tumour necrosis was above 90% in 9 patients, 60-90% in 12, and less than 60% in 7 patients. An increase in erbB-4 expression was more common in cases with no response to chemotherapy, while no change or a decrease in erbB-4 was more common in responsive tumours (P=0.004). No correlation could be found between the degree of necrosis or the chemotherapeutic regimen and the change in expression of erbB-4. The median disease-free survival (DFS) was longer for patients with a decrease or no change in expression of erbB-4 than for patients with increased expression. It is believed that postchemotherapy new expression or no downregulation of the erbB-4 molecule represents tumour aggressiveness and increased capability of growth and spread.