18
Views
7
CrossRef citations to date
0
Altmetric
Research Article

Cell Death in Retinoblastoma: Electron Microscopic, Immunohistochemical, and DNA Fragmentation Studies

, , &
Pages 23-32 | Published online: 10 Jul 2009
 

Abstract

Apparent cell loss by apoptosis occurs in carcinomatous tissue. To investigate cell death in retinoblastoma (Rb), ultrastructural examination, ApopTag staining, electrophoresis to detect apoptotic DNA fragmentation, and flow cytometric studies were performed. Immunostaining for the oncogenic products bcl-2 and p53 was also carried out. Relationships between the proliferation fraction (PF), apoptotic index (AI), and the distribution of bcl-2 and p53 were investigated according to the degree of histologic differentiation of Rb. Ultrastructurally,two patterns of cell death were seen. Necrotic cells exhibited vacuolation of cytoplasmic organelles with a marked lytic change in the karyoplasm and cytoplasm. In contrast, apoptotic cells were characterized by crescentic margination of chromatin, condensation of karyoplasm and cytoplasm, and fragmentation of the nucleus. Differentiated Rb had a low AI value (< 1%),whereas undifferentiated Rb had a high AI value (> 8%). The PF of undifferentiated RB (31%) was significantly higher than that of differentiated RB (14%). Analysis of DNA fragmentation using 3'-end labeling with terminal transferase indicated that undifferentiated Rb has increased DNA cleavage. The distribution of apoptotic bodies within Rb was inversely correlated with the expression of bcl-2. A majority of tumor cells of differentiated Rb were negative for p53, whereas 20-40% of tumor cells of undifferentiated Rb showed a positive reaction for p53. These findings suggest that the degree of susceptibility to apoptosis is closely related to PF, is inversely related to the degree of differentiation of Rb, and is protected by oncogene bcl-2.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.