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      Uveal melanoma: Estimating prognosis

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          Abstract

          Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms “uvea,” “iris,” “ciliary body,” “choroid,” “melanoma,” “uveal melanoma” and “prognosis,” “metastasis,” “genetic testing,” “gene expression profiling.” Relevant English language articles were extracted, reviewed, and referenced appropriately.

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          Most cited references135

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          The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society.

          This study reviews the case-mix characteristics, management, and outcomes of melanoma cases occuring in the U.S. within the last decade. Analyses of the National Cancer Data Base (NCDB) were performed on cases diagnosed between 1985 through 1994. A total of 84,836 cases comprised of cutaneous and noncutaneous melanomas were evaluated. The percentages of melanomas that were cutaneous, ocular, mucosal, and unknown primaries were 91.2%, 5.2%, 1.3%, and 2.2%, respectively. For cutaneous melanomas, the proportion of patients presenting with American Joint Committee on Cancer Stages 0, I, II, III, and IV were 14.9%, 47.7%, 23.1%, 8.9%, and 5.3%, respectively. Factors associated with decreased survival included more advanced stage at diagnosis, nodular or acral lentiginous histology, increased age, male gender, nonwhite race, and lower income. Multivariate analysis identified stage, histology, gender, age, and income as independent prognostic factors. For ocular melanomas, 85.0% were uveal, 4.8% were conjunctival, and 10.2% occurred at other sites. During the study period, there was a large increase in the proportion of ocular melanoma patients treated with radiation therapy alone. For mucosal melanomas, the distribution of head and neck, female genital tract, anal/rectal, and urinary tract sites was 55.4%, 18.0%, 23.8%, and 2.8%, respectively. Patients with lymph node involvement had a poor prognosis. For unknown primary melanomas, the distribution of metastases as localized to a region or multiple sites at presentation was 43.0% and 57.0%, respectively. Surgical treatment of patients with unknown primary site of the melanoma resulted in better survival compared with no treatment. Treatment of early stage cutaneous melanoma resulted in excellent patient outcomes. In addition to conventional prognostic factors, socioeconomic factors were found to be associated with survival.
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            Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death.

            Melanomas are notoriously difficult to classify because of a lack of discrete clinical and pathological stages. Here, we show that primary uveal melanomas surprisingly cluster into two distinct molecular classes based on gene expression profile. Genes that discriminate class 1 (low-grade) from class 2 (high-grade) include highly significant clusters of down-regulated genes on chromosome 3 and up-regulated genes on chromosome 8q, which is consistent with previous cytogenetic studies. A three-gene signature allows biopsy-size tumor samples to be assigned accurately to tumor classes using either array or PCR platforms. Most importantly, this molecular classification strongly predicts metastatic death and outperforms other clinical and pathological prognostic indicators. These studies offer new insights into melanoma pathogenesis, and they provide a practical foundation for effective clinical predictive testing.
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              The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28.

              (2006)
              To report refined rates of death and related outcomes by treatment arm through 12 years after primary treatment of choroidal melanoma and to evaluate characteristics of patients and tumors as predictors of relative treatment effectiveness and time to death. Randomized multicenter clinical trial of iodine 125 ((125)I) brachytherapy vs enucleation conducted as part of the Collaborative Ocular Melanoma Study. Eligible patients were free of metastasis and other cancers at enrollment. All patients were followed up for 5 to 15 years at scheduled examinations for metastasis or another cancer or until death. Decedents were classified by the independent Mortality Coding Committee as having histopathologically confirmed melanoma metastasis, suspected melanoma metastasis without histopathologic confirmation, another cancer but not melanoma metastasis, or no malignancy. Deaths from all causes and deaths with histopathologically confirmed melanoma metastasis. Within 12 years after enrollment, 471 of 1317 patients died. Of 515 patients eligible for 12 years of follow-up, 231 (45%) were alive and clinically cancer free 12 years after treatment. For patients in both treatment arms, 5- and 10-year all-cause mortality rates were 19% and 35%, respectively; by 12 years, cumulative all-cause mortality was 43% among patients in the (125)I brachytherapy arm and 41% among those in the enucleation arm. Five-, 10-, and 12-year rates of death with histopathologically confirmed melanoma metastasis were 10%, 18%, and 21%, respectively, in the (125)I brachytherapy arm and 11%, 17%, and 17%, respectively, in the enucleation arm. Older age and larger maximum basal tumor diameter were the primary predictors of time to death from all causes and death with melanoma metastasis. Longer follow-up of patients confirmed the earlier report of no survival differences between patients whose tumors were treated with (125)I brachytherapy and those treated with enucleation. Estimated mortality rates by baseline characteristics should facilitate counseling of patients who have choroidal melanoma of a size and in a location suitable for enucleation or (125)I brachytherapy and no evidence of metastasis or another malignancy.
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                Author and article information

                Journal
                Indian J Ophthalmol
                Indian J Ophthalmol
                IJO
                Indian Journal of Ophthalmology
                Medknow Publications & Media Pvt Ltd (India )
                0301-4738
                1998-3689
                February 2015
                : 63
                : 2
                : 93-102
                Affiliations
                [1]Institute for Eye Cancer, L V Prasad Eye Institute, Banjara Hills, Support provided by Operation Eyesight Institute for Eye Cancer (SK) and Hyderabad Eye Research Foundation (SK), Hyderabad, India
                [1 ]Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA
                Author notes
                Correspondence to: Dr. Swathi Kaliki, Institute for Eye Cancer, L V Prasad Eye Institute, Hyderabad - 500 034, Telangana, India. E-mail: kalikiswathi@ 123456yahoo.com
                Article
                IJO-63-93
                10.4103/0301-4738.154367
                4399142
                25827538
                f4f09461-3478-4aa1-80a8-df1388b0cd70
                Copyright: © Indian Journal of Ophthalmology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 March 2014
                : 20 September 2014
                Categories
                Symposium

                Ophthalmology & Optometry
                ciliary body,choroid,eye,iris,melanoma,metastasis,prognosis,tumor,uvea
                Ophthalmology & Optometry
                ciliary body, choroid, eye, iris, melanoma, metastasis, prognosis, tumor, uvea

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