Abstract
Purpose: :
Retinoblastoma is the most common, potentially lethal tumor in children. Different treatments like beam radiation and chemotherapy are used to prevent enucleation. Nevertheless, for both therapy options, resistances are commonly seen. It has been postulated that a subpopulation of CD133 positive cells with enhanced tumorigenicity and stem cell like properties trigger this resistance in tumors. ATP-binding cassette (ABC) transporters act as efflux pumps, and ABCB5, a member of the ABC-B subfamily, identifies cancer stem cells in skin melanoma. Objective of this study is to test, whether there is a difference in expression of CD133 and ABCB5 protein in retinoblastoma tumors resistant to radiation or chemotherapy in comparison to untreated tumors.
Methods: :
Human specimens of seven subjects with retinoblastoma without therapy, seven subjects with prior beam radiation therapy and seven subjects with prior chemotherapy were fixed in formalin, embedded in paraffin and cut in sections. Diagnosis of these specimens was confirmed by histological evaluation. Expression of CD133 and ABCB5 protein was demonstrated by immunohistological co-staining in all specimens.
Results: :
Immunohistochemical analysis showed a higher amount of CD133 and ABCB5 positive cells in prior beam radiation or prior chemotherapy specimens in comparison to untreated specimens. These retinoblastoma cells were cumulated as islets in the tumor.
Conclusions: :
First time, we demonstrated CD133- and ABCB5 positive cells in human retinoblastoma tissue and a higher amount of these cells in beam radiation or chemotherapy treated specimens in comparison to untreated specimens. These data support the concept of a stem cell like subpopulation as a therapy resistant mechanism in retinoblastoma tumor.
Keywords: retinoblastoma • microscopy: light/fluorescence/immunohistochemistry • tumors