EPHA2, EPHA4, and EPHA6 Expression in Uveal Melanomas: Searching for the Culprits of Neoplasia
Abstract
:1. Introduction
1.1. Uveal Melanomas
1.2. The EPH/Ephrin System
2. Materials and Methods
2.1. Immunohistochemistry
2.2. Statistical Analysis
3. Results
3.1. Study Population
3.2. EPHA2 IHC Expression and Association with Clinicopathological Parameters
3.3. EPHA4 IHC Expression and Association with Clinicopathological Parameters
3.4. EPHA6 IHC Expression and Association with Clinicopathological Parameters
3.5. Concurrent Overexpression of EPH2, EPH4, and EPH6
3.6. Survival Analysis
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameter | Median | Range |
---|---|---|
Age | 66.5 | 14–90 years |
Number of Mitoses per 40 HPFs | 3 | 0–24 |
Vertical thickness | 12 | 6–16 mm |
Basal diameter | 16 | 17–24 mm |
Number | % | |
Gender | ||
Male | 17/44 | 39% |
Female | 27/44 | 61% |
Posterior pole involvement | 15/44 | 34% |
Ciliary body involvement | 12/44 | 27% |
Secondary iris involvement | 4/44 | 9% |
Iridocorneal angle involvement | 3/44 | 7% |
Presence of retinal detachment | 18/44 | 41% |
Presence of vitreous hemorrhage | 9/44 | 20% |
Intrascleral involvement | 35/44 | 80% |
Extrascleral involvement | 6/44 | 14% |
Histological cell type | ||
Epithelioid cell | 12/44 | 27% |
Mixed cell | 23/44 | 52% |
Spindle cell | 9/44 | 21% |
Loss of chromosome 3 | 19/29 | 66% |
Gain 8q | 13/17 | 77% |
Presence of metastasis | 17/44 | 39% |
T-category (AJCC) | ||
Τ1 | 0/44 | 0% |
Τ2 | 2/44 | 5% |
Τ3 | 20/44 | 45% |
Τ4 | 22/44 | 50% |
Event | ||
Death of disease | 24/44, within 3–146 months | 55% |
Censored | 20/44, follow-up 1–162 months | 45% |
Cytoplasmic EPHA2 Expression | |||
---|---|---|---|
Low (IRS 0–3) | High (4–12) | p-Value | |
Parameter | Median (range) | ||
Age | 66.5 (14–90) | 70.5 (32–90) | 0.33 |
Number of Mitoses per 40 HPFs | 3 (0–24) | 3 (0–12) | 0.88 |
Thickness | 11.35 (6–16) | 13.35 (8.7–16) | 0.03 |
Basal diameter | 16 (7–24) | 14.5 (14–22) | 0.29 |
Number of cases | |||
Gender | |||
Male | 13 | 4 | 0.74 |
Female | 19 | 8 | |
Posterior pole involvement | |||
No | 21 | 8 | >0.99 |
Yes | 11 | 4 | |
Ciliary body involvement | |||
No | 23 | 9 | >0.99 |
Yes | 9 | 3 | |
Secondary iris involvement | |||
No | 28 | 12 | 0.56 |
Yes | 4 | 9 | |
Iridocorneal angle involvement | |||
No | 29 | 12 | 0.55 |
Yes | 3 | 0 | |
Presence of retinal detachment | |||
No | 17 | 9 | 0.30 |
Yes | 15 | 3 | |
Presence of vitreous hemorrhage | |||
No | 27 | 8 | 0.23 |
Yes | 5 | 4 | |
Intrascleral involvement | |||
No | 9 | 0 | 0.05 |
Yes | 23 | 12 | |
Extrascleral involvement | |||
No | 26 | 12 | 0.17 |
Yes | 6 | 0 | |
Histological cell type | |||
Epithelioid cell | 10 | 2 | 0.36 |
Mixed cell | 17 | 6 | |
Spindle cell | 5 | 4 | |
Loss of chromosome 3 | |||
No | 9 | 1 | >0.99 |
Yes | 16 | 3 | |
Gain 8q | |||
No | 3 | 1 | >0.99 |
Yes | 11 | 2 | |
Presence of metastasis | |||
No | 15 | 10 | 0.09 |
Yes | 10 | 2 | |
T-category (AJCC) | |||
Τ1 | 0 | 0 | >0.99 |
Τ2 | 2 | 0 | |
Τ3 | 14 | 6 | |
Τ4 | 16 | 6 |
EPHA4 Expression | ||||||
---|---|---|---|---|---|---|
Nuclear | Cytoplasmic | |||||
Low (IRS 0–3) | High (4–12) | p-Value | Low (IRS 0–3) | High (4–12) | p-Value | |
Parameter | Median (range) | Median (range) | ||||
Age | 65 (14–90) | 75 (15–87) | 0.33 | 67 (14–90) | 58 (32–90) | 0.84 |
Number of Mitoses per 40 HPFs | 3 (0–24) | 4.5 (0–24) | 0.73 | 3 (0–24 | 3 (2–12) | 0.79 |
Thickness | 11.7 (8.5–16) | 12.2 (6–16) | 0.79 | 11.5 (6–16) | 12.6 (10.5–14.7) | 0.24 |
Basal diameter | 16 (7–24) | 16 (10–20.5) | 0.88 | 16 (7–24) | 15 (12–19.5) | 0.40 |
Number of cases | Number of cases | |||||
Gender | ||||||
Male | 13 | 4 | 0.74 | 16 | 1 | 0.64 |
Female | 19 | 8 | 23 | 4 | ||
Posterior pole involvement | ||||||
No | 21 | 8 | >0.99 | 23 | 3 | >0.99 |
Yes | 11 | 4 | 13 | 2 | ||
Ciliary body involvement | ||||||
No | 25 | 7 | 0.26 | 28 | 4 | >0.99 |
Yes | 7 | 5 | 11 | 1 | ||
Secondary iris involvement | ||||||
No | 30 | 10 | 0.30 | 35 | 5 | >0.99 |
Yes | 2 | 2 | 4 | 0 | ||
Iridocorneal angle involvement | ||||||
No | 31 | 10 | 0.18 | 36 | 5 | >0.99 |
Yes | 1 | 2 | 3 | 0 | ||
Presence of retinal detachment | ||||||
No | 19 | 7 | >0.99 | 24 | 2 | 0.39 |
Yes | 3 | 5 | 15 | 3 | ||
Presence of vitreous hemorrhage | ||||||
No | 26 | 9 | 0.69 | 31 | 4 | >0.99 |
Yes | 6 | 3 | 8 | 1 | ||
Intrascleral involvement | ||||||
No | 6 | 3 | 0.69 | 8 | 1 | >0.99 |
Yes | 26 | 9 | 31 | 4 | ||
Extrascleral involvement | ||||||
No | 26 | 12 | 0.17 | 33 | 5 | >0.99 |
Yes | 6 | 0 | 6 | 0 | ||
Histological cell type | ||||||
Epithelioid cell | 10 | 2 | 0.60 | 12 | 0 | 0.31 |
Mixed cell | 15 | 8 | 20 | 3 | ||
Spindle cell | 5 | 2 | 7 | 2 | ||
Loss of chromosome 3 | ||||||
No | 6 | 4 | 0.39 | 8 | 2 | 0.27 |
Yes | 15 | 4 | 18 | 1 | ||
Gain 8q | ||||||
No | 3 | 1 | >0.99 | 2 | 2 | 0.12 |
Yes | 9 | 4 | 12 | 1 | ||
Presence of metastasis | ||||||
No | 18 | 9 | 0.31 | 23 | 4 | 0.63 |
Yes | 14 | 3 | 16 | 1 | ||
T-category (AJCC) | ||||||
Τ1 | 0 | 0 | 0.74 | |||
Τ2 | 1 | 1 | 2 | 0 | 0.73 | |
Τ3 | 15 | 5 | 17 | 3 | ||
Τ4 | 16 | 6 | 20 | 2 |
EPHA6 Expression | ||||||
---|---|---|---|---|---|---|
Nuclear | Cytoplasmic | |||||
Low (IRS 0–3) | High (4–12) | p-Value | Low (IRS 0–3) | High (4–12) | p-Value | |
Parameter | Median (range) | Median (range) | ||||
Age | 63 (14–90) | 75 (15–90) | 0.03 | 65 (15–90) | 73.5 (14–85) | 0.37 |
Number of Mitoses per 40 HPFs | 4 (0–10) | 2 (0–24) | 0.76 | 3.5 (0–24) | 3 (0–24) | 0.83 |
Thickness | 11.5 (8.5–16) | 12 (6–16) | 0.82 | 11.7 (8.5–16) | 12.5 (6–16) | 0.80 |
Basal diameter | 16 (10–24) | 16 (7–22) | 0.59 | 16.5 (7–24) | 16 (10–20) | 0.54 |
Number of cases | Number of cases | |||||
Gender | ||||||
Male | 18 | 11 | 0.52 | 19 | 10 | 0.74 |
Female | 11 | 4 | 11 | 4 | ||
Posterior pole involvement | ||||||
No | 18 | 11 | 0.52 | 19 | 10 | 0.74 |
Yes | 11 | 4 | 11 | 4 | ||
Ciliary body involvement | ||||||
No | 23 | 9 | 0.28 | 22 | 10 | >0.99 |
Yes | 6 | 6 | 8 | 4 | ||
Secondary iris involvement | ||||||
No | 26 | 14 | >0.99 | 27 | 13 | >0.99 |
Yes | 3 | 1 | 3 | 1 | ||
Iridocorneal angle involvement | ||||||
No | 28 | 13 | 0.26 | 27 | 14 | 0.54 |
Yes | 1 | 2 | 3 | 0 | ||
Presence of retinal detachment | ||||||
No | 14 | 12 | 0.05 | 19 | 7 | 0.51 |
Yes | 15 | 3 | 11 | 7 | ||
Presence of vitreous hemorrhage | ||||||
No | 23 | 12 | >0.99 | 24 | 11 | >0.99 |
Yes | 6 | 3 | 6 | 3 | ||
Intrascleral involvement | ||||||
No | 5 | 4 | 0.46 | 6 | 3 | >0.99 |
Yes | 24 | 11 | 24 | 11 | ||
Extrascleral involvement | ||||||
No | 25 | 13 | >0.99 | 26 | 12 | >0.99 |
Yes | 4 | 2 | 4 | 2 | ||
Histological cell type | ||||||
Epithelioid cell | 10 | 2 | 0.31 | 9 | 3 | 0.70 |
Mixed cell | 13 | 10 | 16 | 7 | ||
Spindle cell | 6 | 3 | 5 | 4 | ||
Loss of chromosome 3 | ||||||
No | 8 | 2 | 0.41 | 6 | 4 | 0.70 |
Yes | 11 | 8 | 13 | 6 | ||
Gain 8q | ||||||
No | 3 | 1 | >0.99 | 1 | 3 | 0.25 |
Yes | 10 | 3 | 9 | 4 | ||
Presence of metastasis | ||||||
No | 16 | 11 | 0.33 | 17 | 10 | 0.51 |
Yes | 13 | 4 | 13 | 4 | ||
T-category (AJCC) | ||||||
Τ1 | 0 | 0 | 0.88 | 0 | 0 | 0.56 |
Τ2 | 1 | 1 | 1 | 1 | ||
Τ3 | 14 | 6 | 15 | 5 | ||
Τ4 | 14 | 8 | 14 | 8 |
Parameter | p-Value |
---|---|
Age (<66.5 vs. ≥66.5 years) | 0.06 |
Number of Mitoses per 40 HPFs (absence vs. presence) | 0.60 |
Vertical thickness (<12 vs. ≥12 mm) | 0.49 |
Basal diameter (<16 vs. ≥16 mm) | 0.94 |
Presence of retinal detachment (no vs. yes) | 0.37 |
Presence of vitreous hemorrhage (no vs. yes) | 0.98 |
Intrascleral involvement (no vs. yes) | 0.06 |
Extrascleral involvement (no vs. yes) | 0.08 |
Histological cell type (epithelioid vs. mixed vs. spindle cell) | 0.47 |
Loss of chromosome 3 (no vs. yes) | 0.03 |
Gain 8q (no vs. yes) | 0.04 |
Presence of metastasis (no vs. yes) | <0.001 |
T-category (AJCC) (T2 vs. T3 vs. T4) | 0.06 |
Ephrin A2 IRS (low vs. high) | 0.40 |
Ephrin A4 nuclear IRS (low vs. high) | 0.60 |
Ephrin A4 cytoplasmic IRS (low vs. high) | 0.19 |
Ephrin A2 nuclear IRS (low vs. high) | 0.62 |
Ephrin A2 cytoplasmic IRS (low vs. high) | 0.98 |
Concurrent high expression of at least two EPHs (no vs. yes) | 0.88 |
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Pergaris, A.; Danas, E.; Gajdzis, P.; Levidou, G.; Gajdzis, M.; Cassoux, N.; Gardrat, S.; Donizy, P.; Korkolopoulou, P.; Kavantzas, N.; et al. EPHA2, EPHA4, and EPHA6 Expression in Uveal Melanomas: Searching for the Culprits of Neoplasia. Diagnostics 2022, 12, 1025. https://doi.org/10.3390/diagnostics12051025
Pergaris A, Danas E, Gajdzis P, Levidou G, Gajdzis M, Cassoux N, Gardrat S, Donizy P, Korkolopoulou P, Kavantzas N, et al. EPHA2, EPHA4, and EPHA6 Expression in Uveal Melanomas: Searching for the Culprits of Neoplasia. Diagnostics. 2022; 12(5):1025. https://doi.org/10.3390/diagnostics12051025
Chicago/Turabian StylePergaris, Alexandros, Eugene Danas, Pawel Gajdzis, Georgia Levidou, Malgorzata Gajdzis, Nathalie Cassoux, Sophie Gardrat, Piotr Donizy, Penelope Korkolopoulou, Nikolaos Kavantzas, and et al. 2022. "EPHA2, EPHA4, and EPHA6 Expression in Uveal Melanomas: Searching for the Culprits of Neoplasia" Diagnostics 12, no. 5: 1025. https://doi.org/10.3390/diagnostics12051025