Original ContributionsAlterations of cell cycle regulators affecting the RB pathway in nonfamilial retinoblastoma*
Section snippets
Patient characteristics and tissues
A cohort of 86 patients with nonfamilial retinoblastoma was included in the study. Fresh and/or paraffin-embedded tissue was collected at the time of enucleation at the “Instituto Nacional de Pediatria” (INP) in Mexico City, Mexico. Children were excluded from the study if they were older than 5 years at diagnosis or had a positive family history of retinoblastoma. None of the children had received any local or systemic therapy before enucleation. Demographic data on the cohort are summarized
Results
Tissue from 86 children with sporadic retinoblastoma was examined by immunohistochemistry for markers of cell cycle progression related to the RB pathway. Detectable pRB in the nuclei of tumor cells was found in 11 of 86 (12.8%) cases (Fig 1).
Discussion
We undertook the present study to examine patterns of expression of critical regulators of the RB pathway, including the phenotypes of pRB, p16, and E2F1 in tumors from a cohort of 86 well-characterized patients with nonfamilial retinoblastoma. We also analyzed the relationship between these phenotypes with Ki67 proliferative index and clinicopathologic parameters of poor outcome, including age at diagnosis, stage, and mortality. Our study shows significant relationships between lack of pRB and
Acknowledgements
The authors thank Dr Roberto Rivera Luna and the staff and patients of the Departments of Ophthalmology, Oncology, and Pathology at the Instituto Nacional de Pediatria, Mexico City, Mexico, for their support and assistance with this study.
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2019, Clinica Chimica ActaCitation Excerpt :As cells enter S phase of the cell cycle Rb becomes hyperphosphorylated and remain in this state throughout cell cycle. Phosphorylated Rb has a negative regulatory effect on gene expression by forming complex with E2F [41]. Ki-67 protein is bound to the E2F proteins.
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2003, American Journal of PathologyCitation Excerpt :Phosphorylation at these sites was also shown to be important for Rb inactivation in cultured melanoma cells. A study on non-familial retinoblastoma tumors also suggested increased Rb phosphorylation in tumor cells that had not lost expression of the protein, consistent with inactivation.58 Examination of a series of gynecologic squamous intraepithelial lesions using a phospho-histone 1 antibody revealed patterns generally similar to those observed using MIB-1.59
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Supported by grants NCI-CA-47538 and NCI-CA-47179 (C.C.C.) and by the Bowen Brooks Foundation, New York Academy of Medicine (M.O.).