Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Samples
2.2. Immunohistochemistry
2.3. Gene Expression Classification
2.4. Digital Image Analysis
- (1)
- Full section. The proportion of BAP-1 positive tumor cells in the entire tumor cross-section.
- (2)
- Hot spot. The circular region with a diameter of 0.5 mm (corresponding to an area of 0.2 mm2 per tumor, or one high-power field in a light microscope at 400×) with the highest proportion of BAP-1 positive tumor cells in any part of the tumor.
- (3)
- Cold spot. The circular region with a diameter of 0.5 mm with the lowest proportion of BAP-1 positive tumor cells in any part of the tumor.
- (4)
- Scleral margin. The circular region with a diameter of 0.5 mm with the lowest proportion of BAP-1 positive tumor cells within 1 mm from the tumor base towards the sclera.
2.5. Statistical Methods
3. Results
3.1. Descriptive Statistics
3.2. Intratumor Heterogeneity in BAP-1 Expression
3.2.1. Full Sections
3.2.2. Hot Spots
3.2.3. Cold Spots
3.2.4. Scleral Margins
3.2.5. Heterogeneity
3.3. Sensitivity and Specificity for Gene Expression Class and Metastasis
3.4. Survival
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
- The Royal Swedish Academy of Sciences (reference ME2019-0036)
- The Swedish Cancer Society (20 0798 Fk)
- The Swedish Society of Medicine (Cronqvists stiftelse, reference SLS 934014)
- The Swedish Eye Foundation (reference 2020-04-27)
- Karolinska Institutet (reference 2019-01900, 2020-013333 and 2020-02517)
- Region Stockholm (reference 20200356)
- The Crown Princess Margareta Foundation for the Visually Impaired (reference 157)
- Carmen and Bertil Regnér Foundation (reference 2020-00062)
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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n = | 40 |
---|---|
Mean age at diagnosis, years (min—max) | 64 (24–92) |
Sex, n (%) | |
Female | 22 (55) |
Male | 18 (45) |
Cell type, n (%) | |
Spindle | 6 (15) |
Epithelioid | 8 (20) |
Mixed | 26 (65) |
Mean tumor thickness, mm (SD) | 8.8 (3.4) |
Mean tumor diameter, mm (SD) | 15.1 (3.7) |
Tumor location, n (%) | |
Choroid only | 31 (78) |
Ciliary body only | 0 (0) |
Iris only | 0 (0) |
Choroid and ciliary body | 7 (18) |
Ciliary body and iris | 0 (0) |
Choroid, ciliary body and iris | 2 (5) |
Previous brachytherapy, n (%) | |
No | 38 (95) |
Yes | 2 (5) |
AJCC T-category, n (%) | |
1a–d | 1 (3) |
2a | 8 (20) |
2b | 2 (5) |
2c,d | 0 (0) |
3a | 16 (40) |
3b | 5 (13) |
3c,d | 0 (0) |
4a | 6 (15) |
4b | 2 (5) |
4c,d | 0 (0) |
AJCC stage, n (%) | |
I | 1 (3) |
IIA | 8 (20) |
IIB | 18 (45) |
IIIA | 11 (28) |
IIIB | 2 (5) |
IIIC | 0 (0) |
IV | 0 (0) |
Gene expression class, n (%) | |
1a | 10 (25) |
1b | 8 (20) |
2 | 9 (23) |
Na | 13 (33) |
Follow-up months, median (SD) | 52 (105) |
Tumor Area | AUC | S.E. | p | Asymptotic 95% CI | Cutoff * | Sensitivity | Specificity | |
---|---|---|---|---|---|---|---|---|
Lower Bound | Upper Bound | |||||||
(a) | ||||||||
Full section | 0.89 | 0.050 | <0.0001 | 0.80 | 0.99 | 68% | 88% | 79% |
Hot spots | 0.86 | 0.065 | <0.0001 | 0.73 | 0.98 | 46% | 81% | 92% |
Cold spots | 0.86 | 0.060 | <0.0001 | 0.73 | 0.96 | 93% | 75% | 75% |
Scleral margins | 0.86 | 0.058 | <0.0001 | 0.74 | 0.97 | 89% | 81% | 75% |
(b) | ||||||||
Full section | 0.86 | 0.078 | 0.002 | 0.70 | 1.00 | 61% | 100% | 83% |
Hot spots | 0.85 | 0.071 | 0.002 | 0.72 | 0.99 | 33% | 82% | 83% |
Cold spots | 0.85 | 0.071 | 0.001 | 0.71 | 0.99 | 93% | 82% | 78% |
Scleral margins | 0.86 | 0.069 | 0.002 | 0.73 | 0.99 | 91% | 82% | 73% |
Tumor Area | B | S.E. | Wald | p | Exp(B) | 95% CI | |
---|---|---|---|---|---|---|---|
Lower | Upper | ||||||
Full section | 2.8 | 0.8 | 12.9 | <0.001 | 15.7 | 3.5 | 70.8 |
Hot spots | 2.5 | 0.6 | 15.1 | <0.001 | 12.4 | 3.5 | 43.9 |
Cold spots | 1.8 | 0.6 | 9.7 | 0.002 | 6.2 | 2.0 | 19.5 |
Scleral margins | 1.9 | 0.6 | 8.9 | 0.003 | 6.8 | 1.9 | 24.1 |
Tumor Area | LRΔχ2 | p |
---|---|---|
(a) | ||
Full section | 21.0 | <0.001 |
Hot spots | 20.9 | <0.001 |
Cold spots | 11.6 | 0.001 |
Scleral margins | 11.8 | 0.001 |
(b) | ||
Full section | 8.4 | 0.004 |
Hot spots | 12.0 | <0.001 |
Cold spots | 4.1 | 0.04 |
Scleral margins | 12.0 | <0.001 |
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Stålhammar, G.; Grossniklaus, H.E. Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression. Cancers 2021, 13, 1143. https://doi.org/10.3390/cancers13051143
Stålhammar G, Grossniklaus HE. Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression. Cancers. 2021; 13(5):1143. https://doi.org/10.3390/cancers13051143
Chicago/Turabian StyleStålhammar, Gustav, and Hans E. Grossniklaus. 2021. "Intratumor Heterogeneity in Uveal Melanoma BAP-1 Expression" Cancers 13, no. 5: 1143. https://doi.org/10.3390/cancers13051143