HSP27 EXPRESSION IN NEUROBLASTOMA - CORRELATION WITH DISEASE STAGE

Background: The 27-kd heat shock protein (Hsp27) is differentially exp ressed in some malignancies, including breast carcinoma, leukemia, and malignant fibrous histiocytoma. In breast carcinoma, a high-level exp ression of Hsp27 has been associated with shorter disease-free surviva l in patients with localized disease. Purpose: We have observed variab le levels of Hsp27 among neuroblastoma tumors. Our aim in this study w as to investigate the relationship between Hsp27 expression and stage of the disease and N-myc gene copy number. Methods: We determined Hsp2 7 protein levels in 53 neuroblastoma tumors representing different sta ges of the disease and in 17 neuroblastoma cell lines by quantitative two-dimensional polyacrylamide gel electrophoresis (PAGE). We also per formed statistical analysis of Hsp27 levels in relation to stage of th e disease and to N-myc gene copy number. Results: Increased Hsp27 expr ession in neuroblastomas was associated with limited stage disease and inversely correlated with N-myc gene amplification, a feature known t o predict poor clinical outcome. An inverse correlation was also obser ved between N-myc gene amplification and Hsp27 protein levels among th e neuroblastoma cell lines analyzed. Immunohistochemical staining of s ections of neuroblastomas showed that Hsp27 was most prominently expre ssed in the cytoplasm of large ganglionic tumor cells present in neuro nally differentiated areas of the tumors. Induction of neuronal differ entiation in SMS-KCNR neuroblastoma cells using retinoic acid resulted in an increase in Hsp27. Conclusion: High level expression of Hsp27 i n neuroblastoma is a feature of limited stage, differentiated tumors. Implication: Hsp27 mag play a part in the biology of neuroblastomas wi th a favorable outcome.