ARTICLES Increased Ras Expression and Caspase-Independent Neuroblastoma Cell Death: Possible Mechanism of Spontaneous Neuroblastoma Regression

sion frequently during its natural course. Although pro-grammed cell death (PCD) has been implicated in this pro-cess, accumulating evidence suggests that apoptosis, a form of PCD that is regulated by caspases, may not play a major role. We examined the mechanism(s) of spontaneous regres-sion of neuroblastoma, focusing on the role of Ras, a favor-able prognostic marker of neuroblastoma. Methods: Tumor tissues were analyzed by light microscopy, electron micros-copy, and immunohistochemistry to examine cell degenera-tion and expression of Ras and several indicators of PCD. Cell degeneration was also studied in vitro in neuroblastoma cells transfected with the H-ras gene. All statistical tests were two-sided. Results: Immunohistochemical analyses revealed that Ras expression was increased in areas of cellular degen-eration lacking apoptotic characteristics. The degeneratin