Altered expression of rb and p53 in uveal melanomas following plaque radiotherapy

• Published in: American journal of ophthalmology 2002-02, Vol.133 (2), p.242-248
• Main Authors: Brantley, Milam A, Worley, Lori, Harbour, J.William
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Brachytherapy; Cobalt Radioisotopes - therapeutic use; Cyclin D1 - metabolism; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; DNA Damage; DNA, Neoplasm - radiation effects; Eye Enucleation; Female; Humans; Immunoenzyme Techniques; Iodine Radioisotopes - therapeutic use; Male; Medical sciences; Melanoma - metabolism; Melanoma - pathology; Melanoma - radiotherapy; Middle Aged; Nuclear Proteins; Ophthalmology; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism; Proto-Oncogene Proteins c-mdm2; Retinoblastoma Protein - metabolism; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - metabolism; Tumors and pseudotumors of the eye, orbit, eyelid, lacrimal apparatus; Uveal Neoplasms - metabolism; Uveal Neoplasms - pathology; Uveal Neoplasms - radiotherapy
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/S0002-9394(01)01362-9

PURPOSE : 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.