In reply to “Comment on: F. Sandra et al., The role of MDM2 in the proliferative activity of ameloblastoma”, Oral Oncology 2002;38(2):153–7

Abstract

We appreciate the comments of Iain O’Neill on our article ‘‘The role of MDM2 in the proliferative activity of ameloblastoma’’. In his comments, the statement of ‘‘p53 is not related to the proliferation of ameloblastoma’’ was questioned. It is now well established that p53 functions to prevent aberrant replication of genetic material during cell division. In our studies, we detected expression of p53 in ameloblastoma. But in our study, we found that the p53 labeling indices correlated neither with WHO classification nor the cytological pattern of the outer layer cells of ameloblastoma. Previously we had studied proliferative activity of ameloblastoma using proliferation markers, PCNA and Ki-67. In those studies, we could find differences in PCNA and Ki67 labeling indices in each type of the classification that were in accordance with the WHO classification and the cytological pattern of outer layer cells of ameloblastoma. Hence, one of the reasons for our conclusion that p53 is not related to the proliferation of ameloblastoma. Furthermore, we also extended our studies to search for possible p53 mutants which might cause the abberant expression of wild type p53, but we detected p53 mutants only in 2 of our 14 cases. On the other hand, MDM2, which modulates p53 tumor suppressor activity and mediates p53 degradation by shuttling p53 from nucleus to cytoplasm, was found to be related to/mimic the labeling index order of PCNA and Ki-67. Therefore, MDM2 might be one of the other disruptions in the complex p53 pathways that causes the aberrant expression of p53. Surely, we agree with O’Neil’s comments that based on our studies we can only conclude that the presence of MDM2 proteins appear to be of significance and putatively involved in the epithelial proliferation of ameloblastoma. However, we also have not detected any change in the expression of p53 that would shed some light to the order of PCNA and Ki-67 expression. Therefore, our studies suggest that p53 might have a function in the cell cycle, but its function might be repressed or degraded by MDM2. The statement that p53 is not related to proliferation of ameloblastoma could be concluded by understanding the possible role of MDM2 on p53 degradation. While our studies demonstrate that the expression of p53 may not be related to the proliferation indices, we agree that changes in the other components of the p53 complex may be involved.