Original articleAltered expression of rb and p53 in uveal melanomas following plaque radiotherapy1☆,
Section snippets
Tumor samples
Nine eyes of nine patients were identified by computer search to have undergone enucleation for posterior uveal melanoma following 125I or 60Co plaque radiotherapy between 1993 and 2001 at the Washington University Medical Center. In addition, tumor tissue was obtained prospectively for use in cell culture and cytogenetic studies from three eyes in three additional patients who required enucleation following 125I plaque radiotherapy (none of these had clinical evidence of local tumor
Results
The study included twelve uveal melanomas that had been treated with 125I (11 cases) or 60Co (1 case) plaque radiotherapy and subsequently required enucleation due to radiation complications (5 cases), local recurrence (3 cases), postoperative infection (1 case), corneal opacity (1 case), periocular pain (1 case), and patient request (1 case) (Table 1). Histopathologically, variable loss of tumor tissue was evident in all cases, although residual tumor cells could be identified in all 12 cases
Discussion
A major goal of radiation oncology is to induce “reproductive cell death” by rendering tumor cells incapable of proliferation or metastasis and triggering sustained cell death that corresponds to the regression of the tumor mass that is observed clinically.10, 11 In this study, we provide evidence that reproductive death occurs frequently in uveal melanomas following plaque radiotherapy and we present initial insights into potential molecular mechanisms for this phenomenon.
We found residual
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Cited by (23)
The roles of mouse double minute 2 (MDM2) oncoprotein in ocular diseases: A review
2022, Experimental Eye ResearchCitation Excerpt :MDM2 expression was also enhanced in response to a physiological accumulation of WT p53. Thirty-three percent of 12 irradiated tumors displayed abnormal RB staining patterns of weak nuclear staining and variable cytoplasmic staining, possibly indicating RB mutation (Brantley et al., 2002). Another immunohistochemical study of 96 uveal melanomas from enucleated eyes demonstrates that MDM2 immunoreactivity of tumor cells is potentially associated with the development of metastases with an odds ratio of 2.1 (Coupland et al., 2000).
Expression of p53-induced apoptosis effector PERP in primary uveal melanomas: Downregulation is associated with aggressive type
2006, Experimental Eye ResearchCitation Excerpt :However, p53 mutation or loss of heterozygosity are infrequent events in untreated uveal melanomas (Kishore et al., 1996; Brantley and Harbour, 2000) and therefore cannot explain the functional inactivation of p53 pathway in this tumor. Moreover, there is extensive evidence that the upstream signaling to p53 in uveal melanoma cells is functional and, furthermore, that p53 expression is increased, as expected, in response to DNA damage induced by irradiation of cultured cells and in primary tumors (Brantley et al., 2002; Sun et al., 2005). Hence, the deregulation of p53 downstream effectors emerges as a plausible and common strategy employed by uveal melanomas to acquire resistance to apoptosis.
Missense mutations in cancer suppressor gene TP53 are colocalized with exonic splicing enhancers (ESEs)
2004, Mutation Research - Fundamental and Molecular Mechanisms of MutagenesisTowards fast and inexpensive molecular diagnostic: The case of TP53
2004, Clinica Chimica Acta
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This work was supported by NIH grants K08 EY00382-01 and R01 EY13169-01. Dr. Harbour was supported by a Career Development Award from Research to Prevent Blindness, Inc.
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The author has no proprietary interest in this study.