Altered expression of Rb and p53 in uveal melanomas following plaque radiotherapy.
OBJECTIVE
To examine the expression of proteins in the Rb and p53 tumor suppressor pathways in uveal melanomas following plaque radiotherapy.


METHODS
Immunohistochemistry and cell culture studies. Immunohistochemistry for Rb, p16, cyclin D1, p53, HDM2, and Bcl-2 was performed on twelve eyes containing posterior uveal melanomas that were enucleated following plaque radiotherapy. Cell culture studies were performed in three cases.


RESULTS
The irradiated eyes were enucleated for radiation complications (five cases), local tumor recurrence (three cases), and other reasons (four cases). On histopathologic examination, all cases showed evidence of tumor cell loss. However, residual tumor cells were present in all cases, including those that were clinically regressed. Residual cells from three of the clinically regressed cases were cultured and demonstrated minimal cell division, marked cell death, and extensive chromosomal damage. Strong p53 staining was observed in six cases (50%) and was significantly associated with recent radiotherapy (P = .04). Abnormal cytoplasmic staining for Rb was observed in four cases (33%).


CONCLUSIONS
Plaque radiotherapy of uveal melanomas induces DNA damage, inhibits cell division, and promotes cell death. These changes may be due, at least in part, to induction of p53, which activates genes involved in both cell cycle arrest and apoptosis. Plaque radiotherapy can also cause alterations in the expression of Rb, but the significance of this finding will require further study.
Brantley
Milam A
MA
Center for Ocular Oncology, Department of Ophthalmology and Visual Sciences and Division of Molecular Oncology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Worley
Lori
L
Harbour
J William
JW
D000328:Adult; D000368:Aged; D001918:Brachytherapy; D003037:Cobalt Radioisotopes / Q000627:therapeutic use; D019938:Cyclin D1 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000528:radiation effects; D015353:Eye Enucleation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D008875:Middle Aged; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D016160:Retinoblastoma Protein / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014604:Uveal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy
D003037:Cobalt Radioisotopes; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D007457:Iodine Radioisotopes; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2