uveal melanoma ( um ) is the most common primary intraocular malignant tumor in adults , as well as the most common noncutaneous melanoma . this tumor primarily affects caucasians and has an incidence of approximately 6 cases per million . the leading cause of death in um patients  can be present at the same time as the diagnosis of the primary tumor or several years thereafter [ 2 , 3 ] . tumor metastasis occurs via hematogenous dissemination , with the liver being the most common organ affected , followed by lung and bone [ 4 , 5 ] . metastasis suppressor genes ( msgs ) are known to play a role in numerous cancers . they are of particular interest to researchers given that they can be implicated in various steps of the metastatic cascade and thus may have therapeutic value . the msg kai1 has previously been shown to interfere with multiple steps of the metastatic cascade , including proliferation , invasion , and migration , making it an attractive marker to evaluate in um and other cancers [ 7 , 8 ] . multiple studies have demonstrated that the expression of kai1 in some primary tumor types is inversely correlated with formation of metastasis . the aim of this study was to investigate the expression of kai1 in cases of primary human uveal melanomas and to determine possible correlations with the development of metastatic disease . formalin - fixed , paraffin - embedded sections from 18 enucleated eyes of um patients were used in this study . inclusion criteria included the following : ( 1 ) diagnosis of choroidal melanoma , ( 2 ) minimum follow - up of 12 months , and ( 3 ) sufficient material for immunohistochemical analysis . the processing of barcode - labeled slides included baking of the slides , solvent - free deparaffinization , and cc1 ( tris - edta buffer , ph 8.0 ) antigen retrieval . slides were incubated with a kai1 antibody ( santa cruz biotechnology , sc-17752 , g-2 , 1  :  100 ) for 30 minutes at 37c , followed by application of a biotinylated secondary antibody ( 8 minutes at 37c ) and an avidin - alkaline phosphatase enzyme conjugate complex ( 8 minutes at 37c ) . finally , the antibody was detected by fast red chromogenic substrate and counterstained with hematoxylin . as positive controls , sections of breast cancer were used . for negative controls , the primary antibody was omitted . sections of choroidal melanomas were graded semiquantitatively for kai1 expression based on the intensity ( negative = 0 ; mild = 1 ; strong = 2 ) and extent ( negative = 0 ; focal , < 30%  of  cells positive = 1 ; diffuse , > 30%  of  cells a combined score was used to separate the patients into two groups according to staining characteristics : group 1 , total score of 0 to 2 , and group 2 , total score of 3 or 4 . eighteen cases of uveal melanoma were studied and the patients were followed up after enucleation for an average of 66.38 months ( median : 66 months ) ( table 1 ) . the patients were divided into two groups according to the staining score . from the six cases in group 1 , the mean follow - up time in this group was 56.83 months ( median : 54 months ) , compared to 71.16 months ( median : 72.5 months ) in group 2 . in the high staining group , 2 of the 12 cases presented with metastasis . conversely , in the low staining group , 5 out of 6 cases had metastasis . the mean follow - up of patients who did not develop metastasis was 81.81 months ( median : 75 months ) versus 42.14 months ( median : 44 months ) for patients with metastasis ( figure 1 ) . to determine whether or not there was a statistically significant association between low kai1 staining and the development of metastasis , we used fisher 's exact test . we found a significant association ( p value of 0.0072 ) ; however , since the sample size was small , the statistical power of this test is low ( 0.179 ) . it is believed that downregulation of msgs is a critical step to enable tumor cells to complete the metastatic cascade . to date , a total of thirteen msgs have been characterized in cancer in general , although research on the potential prognostic and therapeutic value of msgs in um is not well characterized [ 10 , 11 ] . to the best of our knowledge , this is the first time that kai1 has been characterized in uveal melanoma . although it is known that metastasis can occur several years after the diagnosis of the primary tumor , mean follow - up time of patients in this study that did not present with metastasis was nearly twice as long as the follow - up time of patients with metastatic disease . this difference in follow - up time is related to the relatively short survival time for patients diagnosed with metastasis . in this study , patients that had a combined score of 3 or 4 were significantly less likely to develop metastasis . these data corroborate previous studies that similarly demonstrated such association in other malignancies such as prostate , gastric , colon , cervical , breast , skin , bladder , lung , pancreatic , liver , and thyroid cancers . while much has been learned about kai1 , a lot remains to be determined about its function , particularly with respect to its role as a metastasis suppressor . nevertheless , the initial findings presented in this study highlight kai1 as a putative regulator of metastasis in um patients . more research is needed to determine the potential of kai1 as a diagnostic marker or clinical target in um . this is due to changes in the clinical management of ums , many of which are treated with brachytherapy rather than undergoing enucleation . thus , while these preliminary results point to an association between low staining of kai1 and the development of metastasis , more cases will need to be studied to achieve a higher power result . given that fine - needle aspiration biopsy ( fnab ) of um is becoming more commonplace , the identification of putative prognostic markers that can be evaluated in fnab specimens has important clinical implications . further research will confirm whether or not kai1 could serve as such a prognostic marker in um .
introduction . uveal melanoma ( um ) is an intraocular tumor that leads to metastatic disease in approximately 50% of afflicted patients . 
 there is no efficacious treatment for metastatic disease in this cancer . 
 identification of markers that can offer prognostic and therapeutic value is a major focus in this field at present . 
 kai1 is a metastasis suppressor gene that has been reported to play a role in various human malignancies , although it has not previously been evaluated in um . 
 purpose . to investigate the expression of kai1 in um and its potential value as a prognostic marker . 
 materials and methods . 
 18 cases of human primary um were collected and immunostained for kai1 expression . a pathologist evaluated staining intensity and distribution semiquantitatively . each case 
 was categorized as group 1 ( low staining ) or group 2 ( high staining ) . 
 results . in group 2 , two of the 12 cases presented with metastasis . 
 conversely , in group 1 , five out of 6 cases had metastasis . 
 the mean follow - up of patients who did not develop metastasis was 81.81 months ( median : 75 months ) versus 42.14 months ( median : 44 months ) for patients with metastasis . 
 conclusions . 
 kai1 is a promising candidate marker that may offer prognostic value in um ; it may also represent a therapeutic target in metastatic disease .