*4.3.8 Genetic markers*

The mitogen-activated protein kinase (MAPK) pathway is one of the main regulatory pathways involved in choroidal melanoma development, particularly through mutations in BRAF, NRAS, and KIT. Choroidal melanoma with BRAF mutation is common in younger patients and the ones associated with preexisting nevi. KIT mutations are the least common choroidal melanoma mutation in MAPK pathway. NRAS mutation is very rare in choroidal melanoma [21–33]. Disomy 3 and chromosome 6p gain are associated with a good prognosis.

Chromosome 3 loss, 8q gain, 1p loss and 6q loss = Class 1 associated with poor prognosis.

Based on gene expression prolifes (GEP), uveal melanoma is now classified into three prognostic categories for metastasis (**Table 6**).

The GEPs are playing a major role at present in prognosticating the risk of metastasis. The tumor as such is constantly evolving at the genetic and molecular level which is described as intratumoral genetic heterogeneity. The term cresendo malignancy is described which explains the transformation of a small tumor which is slow growing over years but acquires Class 2 genetic changes over time (**Table 6**).


**Table 6.** *Prognostic categories for metastasis.*


**Table 7.**

2. Secondary outcome: Metastasis-free survival, cancer-free survival, and years

1.Pre-enucleation EBRT for large melanoma has no advantage over enucleation group. Five-year Kaplan–Meier estimates for survival were 57% for the enucleation group and 62% for the pre enucleation radiation group.

2.Enucleation versus brachytherapy for medium melanoma were comparable. The cumulative all-cause mortality at 12 years was 43% for patient in the plaque radiotherapy group versus 41% for those in enucleation group.

3.The small tumor trial showed that small choroidal melanomas managed by observation showed tumor growth in 21% by 2 years and 31% by 5 years. Observation for small melanoma is not acceptable now and is treated

The mitogen-activated protein kinase (MAPK) pathway is one of the main regulatory pathways involved in choroidal melanoma development, particularly through mutations in BRAF, NRAS, and KIT. Choroidal melanoma with BRAF mutation is common in younger patients and the ones associated with preexisting nevi. KIT mutations are the least common choroidal melanoma mutation in MAPK pathway. NRAS mutation is very rare in choroidal melanoma [21–33]. Disomy 3 and

Chromosome 3 loss, 8q gain, 1p loss and 6q loss = Class 1 associated with poor

Based on gene expression prolifes (GEP), uveal melanoma is now classified into

**Systemic metastasis at 5 years**

The GEPs are playing a major role at present in prognosticating the risk of metastasis. The tumor as such is constantly evolving at the genetic and molecular level which is described as intratumoral genetic heterogeneity. The term cresendo malignancy is described which explains the transformation of a small tumor which is slow growing over years but acquires Class 2 genetic changes over time (**Table 6**).

Class 1A Low risk 2% Class 1B Intermediate risk 21% Class 2 High risk 72%

of useful vision

Results:

*Melanoma*

appropriately.

*4.3.8 Genetic markers*

prognosis.

**Table 6.**

**46**

*Prognostic categories for metastasis.*

Trial design and treatment groups:

1.Small <3 (1.5–2.4) mm, 5 mm (observational group)

3.Large >8 (10 mm), >16 mm (randomized group)

chromosome 6p gain are associated with a good prognosis.

three prognostic categories for metastasis (**Table 6**).

2.Medium 3–8 (2.5–10) mm, 16 mm (randomized group)

*Metastasis depends on several factors: Size, markers-BAPI, and genetics [34].*
