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| | align="center" style="background:#f0f0f0;" |'''Prognostic Factor'''
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| | align="center" style="background:#f0f0f0;" |'''Description'''
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| |'''Age'''||>60 years of age is associated with poor prognosis<ref name="pmid2208011">{{cite journal| author=Augsburger JJ, Gamel JW| title=Clinical prognostic factors in patients with posterior uveal malignant melanoma. | journal=Cancer | year= 1990 | volume= 66 | issue= 7 | pages= 1596-600 | pmid=2208011 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2208011 }} </ref>
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| |'''Larger tumor size'''||The mortality rate for small (< 2 - 3 mm apical height), medium (3 - 8 mm apical height) and large (> 8 mm apical height) melanoma is 16%, 32% and 53% in 5 years, respectively.<ref name="vanKoopmans2013">{{cite journal|last1=van|first1=J.G.M.|last2=Koopmans|first2=A.E.|last3=Verdijk|first3=R.M.|last4=Naus|first4=N.C.|last5=de|first5=A.|last6=Kilic|first6=E.|title=Diagnosis, Histopathologic and Genetic Classification of Uveal Melanoma|year=2013|doi=10.5772/53631}}</ref><ref name="pmid12470140">{{cite journal| author=Gragoudas E, Li W, Goitein M, Lane AM, Munzenrider JE, Egan KM| title=Evidence-based estimates of outcome in patients irradiated for intraocular melanoma. | journal=Arch Ophthalmol | year= 2002 | volume= 120 | issue= 12 | pages= 1665-71 | pmid=12470140 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12470140 }} </ref><ref name="pmid16344433">{{cite journal| author=Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD et al.| title=Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. | journal=Arch Ophthalmol | year= 2005 | volume= 123 | issue= 12 | pages= 1639-43 | pmid=16344433 | doi=10.1001/archopht.123.12.1639 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16344433 }} </ref><ref name="pmid23664467">{{cite journal| author=Shields CL, Kaliki S, Furuta M, Fulco E, Alarcon C, Shields JA| title=American Joint Committee on Cancer classification of posterior uveal melanoma (tumor size category) predicts prognosis in 7731 patients. | journal=Ophthalmology | year= 2013 | volume= 120 | issue= 10 | pages= 2066-71 | pmid=23664467 | doi=10.1016/j.ophtha.2013.03.012 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23664467 }} </ref><ref name="pmid23816968">{{cite journal| author=Kujala E, Damato B, Coupland SE, Desjardins L, Bechrakis NE, Grange JD et al.| title=Staging of ciliary body and choroidal melanomas based on anatomic extent. | journal=J Clin Oncol | year= 2013 | volume= 31 | issue= 22 | pages= 2825-31 | pmid=23816968 | doi=10.1200/JCO.2012.45.2771 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23816968 }} </ref><ref name="pmid25555246">{{cite journal| author=AJCC Ophthalmic Oncology Task Force| title=International Validation of the American Joint Committee on Cancer's 7th Edition Classification of Uveal Melanoma. | journal=JAMA Ophthalmol | year= 2015 | volume= 133 | issue= 4 | pages= 376-83 | pmid=25555246 | doi=10.1001/jamaophthalmol.2014.5395 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25555246 }} </ref>
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| |'''Ciliary body involvement'''||Ciliary body involvement is associated with poor prognosis.<ref name="pmid10922199">{{cite journal| author=Li W, Gragoudas ES, Egan KM| title=Metastatic melanoma death rates by anatomic site after proton beam irradiation for uveal melanoma. | journal=Arch Ophthalmol | year= 2000 | volume= 118 | issue= 8 | pages= 1066-70 | pmid=10922199 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10922199 }} </ref>
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| |'''Presence of orange pigment overlying the tumor'''|| Presence of orange pigment overlying tumor is associated with poor prognosis.<ref name="pmid12470140">{{cite journal| author=Gragoudas E, Li W, Goitein M, Lane AM, Munzenrider JE, Egan KM| title=Evidence-based estimates of outcome in patients irradiated for intraocular melanoma. | journal=Arch Ophthalmol | year= 2002 | volume= 120 | issue= 12 | pages= 1665-71 | pmid=12470140 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12470140 }} </ref>
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| |'''Extrascleral extention'''||Extrascleral extension is associated with poor prognosis<ref name="pmid3014416">{{cite journal| author=Gragoudas ES, Seddon JM, Egan KM, Polivogianis L, Hsieh CC, Goitein M et al.| title=Prognostic factors for metastasis following proton beam irradiation of uveal melanomas. | journal=Ophthalmology | year= 1986 | volume= 93 | issue= 5 | pages= 675-80 | pmid=3014416 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3014416 }} </ref><ref name="pmid15519510">{{cite journal| author=Schmittel A, Bechrakis NE, Martus P, Mutlu D, Scheibenbogen C, Bornfeld N et al.| title=Independent prognostic factors for distant metastases and survival in patients with primary uveal melanoma. | journal=Eur J Cancer | year= 2004 | volume= 40 | issue= 16 | pages= 2389-95 | pmid=15519510 | doi=10.1016/j.ejca.2004.06.028 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15519510 }} </ref><ref name="pmid8248556">{{cite journal| author=Kleineidam M, Guthoff R, Bentzen SM| title=Rates of local control, metastasis, and overall survival in patients with posterior uveal melanomas treated with ruthenium-106 plaques. | journal=Radiother Oncol | year= 1993 | volume= 28 | issue= 2 | pages= 148-56 | pmid=8248556 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8248556 }} </ref><ref name="pmid7436829">{{cite journal| author=Affeldt JC, Minckler DS, Azen SP, Yeh L| title=Prognosis in uveal melanoma with extrascleral extension. | journal=Arch Ophthalmol | year= 1980 | volume= 98 | issue= 11 | pages= 1975-9 | pmid=7436829 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7436829 }} </ref>
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| |'''Cell type'''||
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| *Cell type is the most commonly used predictor of outcome following [[enucleation]], with spindle-A cell melanomas carrying the best prognosis and epithelioid cell melanomas carrying the least favorable prognosis. Nevertheless, most tumors have an admixture of cell types, and there is no clear consensus regarding the proportion of epithelioid cells that constitutes designation of a tumor as mixed or epithelioid.
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| *Several additional microscopic features can affect the prognosis of intraocular melanoma, including:<ref name="NIH">Uveal melanoma. National Cancer Institute(2015) http://www.cancer.gov/types/eye/hp/intraocular-melanoma-treatment-pdq#link/_304_toc Accessed on October 23, 2015</ref>
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| |'''Metastasis'''||Histological and cytological factors associated with higher risk of [[metastasis]] includes the following:
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| *Presence and extent of [[cells]] with epitheliod morphology
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| *Presence of looping [[extracellular matrix]] patterns
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| *Increased infiltration of immune cells<ref>Robbins, Stanley L., Vinay Kumar, and Ramzi S. Cotran. Robbins and Cotran pathologic basis of disease. Philadelphia, PA: Saunders/Elsevier, 2010. Print.</ref>
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| *Staining with several immunohistochemical markers<ref name="pmid17425462">{{cite journal| author=Pardo M, Dwek RA, Zitzmann N| title=Proteomics in uveal melanoma research: opportunities and challenges in biomarker discovery. | journal=Expert Rev Proteomics | year= 2007 | volume= 4 | issue= 2 | pages= 273-86 | pmid=17425462 | doi=10.1586/14789450.4.2.273 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17425462 }} </ref>
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| |'''Additional microscopic features that affect the prognosis of intraocular melanoma'''||Several additional microscopic features can affect the prognosis of intraocular melanoma, including:<ref name="NIH">Uveal melanoma. National Cancer Institute(2015) http://www.cancer.gov/types/eye/hp/intraocular-melanoma-treatment-pdq#link/_304_toc Accessed on October 23, 2015</ref>
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| *Mitotic activity.
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| *[[Lymphocytic]] infiltration.
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| *Fibrovascular loops
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| *Extraocular extension, recurrence, and metastasis are associated with an extremely poor prognosis, and long-term survival cannot be expected. Systemic [[metastases]] may be wide spread, with the [[liver]] > [[lung]] > [[bone]] > [[kidney]] > [[brain]] being a common sites for tumor deposits.
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| *Uveal melanoma disseminates hematogenously, with a high propensity for liver, which is the most common (93%) site of metastasizing, followed by [[lung]] (24%) and [[bones]] (16%). It can also metastasize in brain and skin, or any other site in the body. The majority of patients with metastatic disease have metastases in multiple sites of body. Patients without liver metastases or with liver being not the first site of metastases have better prognosis.
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| *Patients with iris melanoma have better prognosis. In patients with iris melanoma at 5 and 10 years of follow up metastases were found in 4.1%, and 6.9%, respectively, compared to 15% and 25%, respectively, for [[choroidal]] [[melanomas]]. [[Ciliary body melanoma]] carries worse prognosis with metastases found at 5 and 10 years follow up in 19% and 33%, respectively.
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| *Uveal melanoma does not spread to regional [[lymph nodes]], due to lack of lymphatic drainage in [[uvea]] except in rare cases of direct invasion of [[conjunctiva]] and then through conjunctival lymphatics to regional lymph nodes. Five-year survival rates for uveal melanoma ranges from 69% to 81.6% and ten-year survival rates from 57% to 62%. After detection of metastases 80% of patients die within 1 year, and 92% within 2 year. Long term survivals are rare in patients with uveal melanoma, and mean survival is only few months.<ref name="pmid23826405">{{cite journal| author=Jovanovic P, Mihajlovic M, Djordjevic-Jocic J, Vlajkovic S, Cekic S, Stefanovic V| title=Ocular melanoma: an overview of the current status. | journal=Int J Clin Exp Pathol | year= 2013 | volume= 6 | issue= 7 | pages= 1230-44 | pmid=23826405 | doi= | pmc=PMC3693189 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23826405 }} </ref>
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| |'''Genetics'''||
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| *The most important genetic alteration associated with poor prognosis in uveal melanoma is inactivation of ''BAP1'', which most often occurs through [[mutation]] of one [[allele]] and subsequent loss of an entire copy of [[chromosome 3]] (monosomy 3 ) to unmask the mutant copy.<ref name="pmid21051595">{{cite journal| author=Harbour JW, Onken MD, Roberson ED, Duan S, Cao L, Worley LA et al.| title=Frequent mutation of BAP1 in metastasizing uveal melanomas. | journal=Science | year= 2010 | volume= 330 | issue= 6009 | pages= 1410-3 | pmid=21051595 | doi=10.1126/science.1194472 | pmc=PMC3087380 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21051595 }} </ref> Because of this function in inactivation of ''BAP1'', monosomy 3 correlates strongly with metastatic spread.<ref name="pmid8622452">{{cite journal| author=Prescher G, Bornfeld N, Hirche H, Horsthemke B, Jöckel KH, Becher R| title=Prognostic implications of monosomy 3 in uveal melanoma. | journal=Lancet | year= 1996 | volume= 347 | issue= 9010 | pages= 1222-5 | pmid=8622452 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8622452 }} </ref>
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| *Where ''BAP1'' [[mutation]] status is not available, gains on chromosomes 6 and 8 can be used to refine the predictive value of the monosomy 3 screen, with gain of 6p indicating a better prognosis and gain of 8q indicating a worse prognosis in disomy 3 [[tumors]].<ref name="pmid19182252">{{cite journal| author=Damato B, Dopierala J, Klaasen A, van Dijk M, Sibbring J, Coupland SE| title=Multiplex ligation-dependent probe amplification of uveal melanoma: correlation with metastatic death. | journal=Invest Ophthalmol Vis Sci | year= 2009 | volume= 50 | issue= 7 | pages= 3048-55 | pmid=19182252 | doi=10.1167/iovs.08-3165 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19182252 }} </ref>
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| *In rare instances, monosomy 3 [[tumors]] may duplicate the ''BAP1''-mutant copy of the [[chromosome]] to return to a disomic state referred to as isodisomy. Thus, isodisomy 3 is prognostically equivalent to monosomy 3, and both can be detected by tests for chromosome 3 [[loss of heterozygosity]].<ref name="pmid17504992">{{cite journal| author=Onken MD, Worley LA, Person E, Char DH, Bowcock AM, Harbour JW| title=Loss of heterozygosity of chromosome 3 detected with single nucleotide polymorphisms is superior to monosomy 3 for predicting metastasis in uveal melanoma. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 10 | pages= 2923-7 | pmid=17504992 | doi=10.1158/1078-0432.CCR-06-2383 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17504992 }} </ref>
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| *Monosomy 3, along with other chromosomal gains, losses, amplifications, and LOH, can be detected in fresh or paraffin embedded samples by virtual [[karyotyping]].
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| *The most accurate prognostic factor is molecular classification by gene expression profiling of uveal melanomas. This analysis has been used to identify two subclasses of uveal melanomas:<ref name="pmid12750282">{{cite journal| author=Tschentscher F, Hüsing J, Hölter T, Kruse E, Dresen IG, Jöckel KH et al.| title=Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities. | journal=Cancer Res | year= 2003 | volume= 63 | issue= 10 | pages= 2578-84 | pmid=12750282 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12750282 }} </ref> <ref name="pmid15492234">{{cite journal| author=Onken MD, Worley LA, Ehlers JP, Harbour JW| title=Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death. | journal=Cancer Res | year= 2004 | volume= 64 | issue= 20 | pages= 7205-9 | pmid=15492234 | doi=10.1158/0008-5472.CAN-04-1750 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15492234 }} </ref>
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| **Class 1 tumors that have a very low risk of [[metastasis]].
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| **Class 2 tumors that have a very high risk of metastasis.
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| **Gene expression profiling outperforms all of the above-mentioned factors at predicting metastatic spread of the primary tumor, including monosomy 3.<ref name="pmid17384575">{{cite journal| author=Petrausch U, Martus P, Tönnies H, Bechrakis NE, Lenze D, Wansel S et al.| title=Significance of gene expression analysis in uveal melanoma in comparison to standard risk factors for risk assessment of subsequent metastases. | journal=Eye (Lond) | year= 2008 | volume= 22 | issue= 8 | pages= 997-1007 | pmid=17384575 | doi=10.1038/sj.eye.6702779 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17384575 }} </ref><ref name="pmid18552379">{{cite journal| author=van Gils W, Lodder EM, Mensink HW, Kiliç E, Naus NC, Brüggenwirth HT et al.| title=Gene expression profiling in uveal melanoma: two regions on 3p related to prognosis. | journal=Invest Ophthalmol Vis Sci | year= 2008 | volume= 49 | issue= 10 | pages= 4254-62 | pmid=18552379 | doi=10.1167/iovs.08-2033 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18552379 }} </ref><ref name="pmid17332290">{{cite journal| author=Worley LA, Onken MD, Person E, Robirds D, Branson J, Char DH et al.| title=Transcriptomic versus chromosomal prognostic markers and clinical outcome in uveal melanoma. | journal=Clin Cancer Res | year= 2007 | volume= 13 | issue= 5 | pages= 1466-71 | pmid=17332290 | doi=10.1158/1078-0432.CCR-06-2401 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17332290 }} </ref>
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| == References == | | == References == |
| {{reflist|2}} | | {{reflist|2}} |
| {{WH}} | | {{WH}} |
| {{WS}} | | {{WS}} |
|
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| [[Category:Disease]]
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| [[Category:Ophthalmology]]
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| |} | | |} |