The effect of Primary Posterior Uveal Melanoma
treatment on serum Bio Marker levels and their
prediction of Metastases
V Barak, S Frenkel, K Hendler, I Kalickman, J Pe’er
Hadassah - Hebrew University Medical Center, Jerusalem, Israel
Background
• Uveal melanoma is the most common primary intraocular
tumor
• It originates in the melanocytes of the uveal tract
• It is usually a tumor of the adult age, with a mean age in
the mid 50s
• Its incidence is 6 – 8 new patients / million / year
• The reported rate of mortality from metastatic uveal
melanoma is up to 20% in 5 years, and up to 50% 15 years after the diagnosis
Background
• Uveal melanoma spreads first and preferentially to
the liver
• Thus, the liver should be the main target for
screening for uveal melanoma metastasis
• The recommended evaluation for metastatic disease
includes:
– Liver imaging (Ultrasound and CT-scan)
– Liver function tests
Study Aims
To asses the impact of treating
Primary Uveal Melanoma on levels of
Biomarkers: OPN, S100 ,TPS, MIA and their
ability to predict metastases
Uveal Melanoma Markers
We have been studying the following
molecules as potential Tumor Markers:
•
•
•
•
OPN
S100β
TPS
MIA
TREATMENTS
•
Enucleation
n = 26
• Brachytherapy
n = 134
• Follow up:
0, 1m, 4m, 10m
TUMOR MARKERS in UVEAL MELANOMA
S-100β
OPN
0.60
20
0.50
16
0.40
S-100β (u/l)
OPN (ng/ml)
24
12
8
4
0.30
0.20
0.10
0
Controls
n=53
DF
n=64
Metastasis
n=37
0.00
Controls
n=51
SE
Mean
MIA
DF
n=64
Metastasis
n=37
SE
Mean
TPS
250
16
14
200
TPS (U/L)
MIA (ng/ml)
12
10
8
6
4
150
100
50
2
0
0
Controls
n=53
DF
n=64
M etastasis
n=37
SE
Mean
Controls
n=53
DF
n=64
Metastasis
n=37
SE
Mean
TUMOR MARKERS in METASTASIS
SE
SE
*
mean
150
16
120
TPS (U/L)
OPN (ng/ml)
*
Mean
20
12
8
4
90
60
30
0
0
pre
post
SE
pre
*
Mean
post
SE
*
Mean
0.50
20
0.45
16
0.35
MIA(ng/ml)
S-100β (μg/L)
0.40
0.30
0.25
0.20
12
8
0.15
0.10
4
0.05
-
0
pre
post
pre
post
OPN and S100 following Brachytherapy
E.M.
B.B.
8.00
30.00
0.20
25.00
0.15
5.00
4.00
0.16
3.00
0.14
0.15
20.00
0.15
0.14
15.00
0.14
10.00
0.14
2.00
1.00
0.00
10.2.04
22.6.04
S100 (u/L)
0.18
OPN (mg/ml)
6.00
S100 (u/L)
OPN (mg/ml)
0.22
0.15
7.00
0.14
0.12
5.00
0.10
0.00
28.12.04
0.13
9.11.04
OPN
Date
0.14
16.3.05
21.9.05
OPN
Date
S100
S100
The effect of therapy on OPN and S100
P.G.
G.Ir.
28.00
0.17
0.12
0.15
0.10
27.00
0.08
0.06
26.00
25.00
24.00
12.12.06
Date
13.03.07
0.13
0.11
0.09
0.07
0.04
0.05
0.02
0.03
10.00
0.00
31.10.06
0.19
OPN (mg/ml)
OPN (mg/ml)
29.00
20.00
0.14
0.01
15.5.07
OPN
S100
S100 (u/L)
0.16
S100 (u/L)
30.00
14.6.07
24.7.07
Date
11.3.08
OPN
S100
LEAD TIME OF MARKERS
MIA (ng/ml)
30
↓
30
25
25
20
20
15
15
10
10
5
5
0
0
8.6.04
7.9.04
Barak V, Frenkel S,Kalickman I, Maniotis A, Folberg
R and Pe'er J
Date
Serum markers to detect metastatic Uveal Melanoma.
Anti Cancer Research, 27:1897 – 1900, 2007
5.4.05
OPN (ng/ml)
CM
MIA
OPN
TPS
140
120
TPS levels
100
80
60
P = 0.07
40
20
0
>24
12-24
6-12
0-6
0
Time before detection of liver metastases (months)
Barak V, Frenkel S, Valyi-Nagy K, Leach L, Apushkin MA, Lin A, Kalickman I, Baumann NA, Pe'er J, Maniotis A, Folberg R
Using the direct injection model of Uveal Melanoma hepatic metastases to identify TPS as a potentially useful
serum biomarker IOVS, 48 (10), 4399 - 402, 2007
ROC (DF)
OPN-83%
MIA-87%
S100-73%
Conclusions
• S-100 and OPN levels decreased significantly after
Enucleation and after Brachytherapy.
• Minor changes were demonstrated in Tumor Markers
levels during 1-10 m after primary treatment.
• Only significant increases (x3- x10) in Marker levels
predict Metastases development in UM patients.