[Show abstract][Hide abstract] ABSTRACT: Uveal (ocular) melanoma is an aggressive cancer that often forms undetectable micrometastases before diagnosis of the primary tumor. These micrometastases later multiply to generate metastatic tumors that are resistant to therapy and are uniformly fatal. We have previously identified a gene expression profile derived from the primary tumor that is extremely accurate for identifying patients at high risk of metastatic disease. Development of a practical clinically feasible platform for analyzing this expression profile would benefit high-risk patients through intensified metastatic surveillance, earlier intervention for metastasis, and stratification for entry into clinical trials of adjuvant therapy. Here, we migrate the expression profile from a hybridization-based microarray platform to a robust, clinically practical, PCR-based 15-gene assay comprising 12 discriminating genes and three endogenous control genes. We analyze the technical performance of the assay in a prospective study of 609 tumor samples, including 421 samples sent from distant locations. We show that the assay can be performed accurately on fine needle aspirate biopsy samples, even when the quantity of RNA is below detectable limits. Preliminary outcome data from the prospective study affirm the prognostic accuracy of the assay. This prognostic assay provides an important addition to the armamentarium for managing patients with uveal melanoma, and it provides a proof of principle for the development of similar assays for other cancers.
The Journal of molecular diagnostics: JMD 04/2010; 12(4):461-8. DOI:10.2353/jmoldx.2010.090220 · 3.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To identify clinical variables prognostic for prompt excision of melanocytic iris tumors and to determine the clinical factors predictive of enlargement of those tumors managed initially by observation.
A retrospective study of 285 patients evaluated in a referral center over a 15-year interval (1972-1986).
Thirty-six lesions were excised promptly, whereas 249 were observed. Eighty-nine percent of the 36 promptly excised tumors were malignant melanomas on histopathologic examination. Five clinical variables were associated strongly with prompt excision: largest basal tumor diameter greater than 3 mm; presence of pigment dispersion; prominent tumor vascularity; elevated intraocular pressure; and tumor-related ocular symptoms. In the observed group, the actuarial 5-year rate of lesion enlargement was 6.5% (standard error = 2.1%). Of the ten lesions that enlarged, six were excised and evaluated histopathologically. Five of these six lesions were malignant melanomas on histopathologic study. Largest basal tumor diameter was the only clinical variable strongly predictive of lesion enlargement. Only two patients died of metastatic uveal melanoma, and both were in the promptly treated group.
Most melanocytic iris tumors are benign and do not enlarge appreciably when followed or lead to metastatic disease. However, even prompt locally effective treatment (excision) is insufficient to prevent metastasis in some patients. Clinical features of the iris lesion appear to enable clinicians to differentiate reasonably well between probable malignant melanomas, for which prompt treatment seems appropriate, and benign nevi, for which observation with periodic follow-up is likely to be the best management.
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