## 3 Results
### Immunohistochemical Expression of SRSF1 and MVD Count in UMs  
Among the whole cohort of 85 UMs, the median SRSF1 value was 2. The better discriminant SRSF1 value as assessed by the Youden index of the ROC curve was 3. SRSF1 expression was high (\(\geq\)3) in 41 and low (<3) in 44 UMs (Figure 1A,B). Among 46 primary non-metastatic UMs, SRSF1 L-IRS was found in 39/46 cases (84.8%), while SRSF1 H-IRS was observed in the remaining 7/46 cases (15.2%) ([PERSON]'s exact test, \(p\) < 0.001, Table 4). In terms of primary metastatic UMs, 5 out of 39 (12.8%) exhibited SRSF1 L-IRS, while 34 out of 39 (87.2%) exhibited SRSF1 H-IRS ([PERSON]'s exact test, \(p\) < 0.001, Table 4). Among the whole cohort of 85 UMs, MVD levels ranged from 11 to 78 (median MVD: 34). The better discriminant SRSF1 value as assessed by the Youden index of the ROC curve was 43. High and low MVD levels were observed in 32 and 53 UMs, respectively. A total of 40/46 (87%) non-metastatic cases exhibited low MVD, while 6/46 (13%) exhibited high MVD ([PERSON]'s exact test, \(p\) < 0.001, Table 4). Moreover, high and low MVD levels were found in 26/39 (66.7%) and 13/39 (33.3%) metastasasing cases, respectively ([PERSON]'s exact test, \(p\) < 0.001, Table 4). Statistical analyses showed that the following factors were related to the metastatic spread at univariate analysis on a Cox proportional hazards regression model: (i) age (\(p\) = 0.011), (ii) diameter (\(p\) = 0.040), (iii) epithelioid cell type (\(p\) = 0.017), (iv) pT stage (\(p\) = 0.023), (v) SRSF1 (\(p\) < 0.001), (vi) MVD levels (\(p\) < 0.001). At multivariate analysis, epithelioid cell type (\(p\) = 0.014), pT stage (\(p\) = 0.001), SRSF1 (\(p\) < 0.001), and MVD (\(p\) < 0.001) were significant. We observed no  
\begin{table}
\begin{tabular}{c c c c c c c c c c c} \hline \hline  & **Sex** & **Age** & **Location** & **Thickness** & **Largest** & **Cell Type** & **Pathological** & **MFS** & **Follow-Up** & **SRSF1** & **MVD** \\  & **m-f** & **(Years)** & & & & **Diameter** & **T stage** & **(Months)** & **(Months)** & **(Months)** & **(**m/mn2**) \\ \hline  & & & & & & pT1a: 15 & & & & \\  & & & & & & pT1b: 4 & & & & \\  & & & & & & pT2a: 44 & & & & \\ All &  
significant correlations between histologic subtype, SRSF1 immunoexpression (Spearman's rho \(p=0.115\)), and MVD (Spearman's rho \(p=0.087\)). A significant correlation was found between SRSF1 IRS and MVD (Spearman's rho \(r=0.322\), \(p=0.007\)). Figure 2 shows the results of the Kaplan-Meier survival analyses in UM patients with low and high SRSF1 immunoexpression. The mean metastasis-free survival times (SE, with 95% CI) estimated were 149.1 (8.3) (CI: 132.9 to 165.3) and 43.1 (6.3) (CI: 30.1 to 55.5); a significant difference (\(p<0.001\)) between the two groups was found by the log-rank test. \begin{table}
\begin{tabular}{c c c c c} \hline  & \multicolumn{2}{c}{**SRSF1**} & \multicolumn{2}{c}{**MVD (n/mm2)**} \\ \hline  & **Low (<3)** & **High (\(\geq\)3)** & **Low (<43)** & **High (\(\geq\)43)** \\ \hline Metastasis free (n = 46) & 39 (84.8\%) & 7 (15.2\%) & 40 (87.0\%) & 6 (13.0\%) \\ \hline Metastasis (n = 39) & 5 (12.8\%) & 34 (87.2\%) & 13 (33.3\%) & 26 (66.7\%) \\ \hline \(p\) ([PERSON]’s exact test) & \textless{}0.001 & \multicolumn{2}{c}{\textless{}0.001} \\ \hline \end{tabular}
\end{table} 
Table 4: Number of uveal melanoma (with and without metastasis) with low and high SRSF1 expression and MVD (n/mm2). Figure 1: (**A**) Strong and diffuse immunohistochemical expression of SRSF1 in a case of spindle cell-type uveal melanoma (immunoperoxidase; original magnification 150\(\times\)); (**B**) Low immunoexpression of SRSF1 in a case of epithellioid cell-type uveal melanoma (immunoperoxidase; original magnification 150\(\times\)). Figure 3 shows the results of Kaplan-Meier survival analyses in patients with uveal melanomas with low and high MVD expression. The mean survival time free from metastasis (SE, with 95% CI) estimated were respectively: 129.0 (9.3) (CI: 110.7 to 147.3) and 35.5 (5.6) (CI: 24.4 to 46.6).