| Protein Markers | Tissue Cypher Features |
|---|---|
| p53, p16, AMACR | Loss of tumor suppression and cell cycle control |
| CD68, COX2 | Immune and inflammatory markers |
| HER-2, CK20 | Cancer growth and cell transformation |
| HIF1alpha, CD45RO | Angiogenesis and memory lymphocyte infiltration |
| Protein Markers | Protein Function |
|---|---|
| p53 | p53 nuclear sum intensity |
| p53 | p53 nuclear mean intensity |
| HER2/neu and K20 | Ratio of mean HER2/neu intensity:mean K20 intensity in nuclei clusters |
| HER2/neu and K20 | Ratio of 95th quantile HER2/neu intensity:95th quantile K20 intensity in nuclei clusters |
| COX-2 and CD68 | Coexpression cellular COX2 mean intensity and cellular CD68, mean intensity |
| p53 | p53 mean intensity in nuclei clusters |
| p53, p16 and nuclear morphology (solidity) | Nuclear solidity in p53+ p16- cells |
| CD45RO | CD45RO plasma membrane sum intensity |
| AMACR | AMACR microenvironment SD |
| COX2 | COX-2 texture in cytoplasm |
| HIF1α | HIF1α microenvironment cell mean intensity |
| HIF1α | HIF1α microenvironment cell moment (product of mean and standard deviation) |
| p16 | p16 cytoplasm mean intensity |
| p53, p16 and nuclear morphology (area) | Nuclear area in p53+ p16- cells |
| Nuclear morphology | Hoechst nuclear 95th quantile intensity |
| Dysplasia grading | 5-year risk (progression to high-grade dysplasia or cancer) | Frequency of surveillance |
|---|---|---|
| Non-dysplastic Barrett’s esophagus | 3.15% | 3-5 years depending on segment length |
| Indefinite for dysplasia (with controlled reflux) | 7.5% | 1-year surveillance |
| Low-grade dysplasia | 8.5% | 6-12-month surveillance or treatment with EET |
 | Other GEP tests | |
|---|---|---|
| Identifies patient risk for nodal metastasis | ✔ | ✔ |
| Provides personalized risk for sentinel lymph node positivity | ✔ | x |
| Provides personalized risk of recurrence including MSS, RFS, and DMFS | ✔ | x |
| Data demonstrates independent, significant risk stratification provided by GEP result compared to AJCC stage | ✔ | x |
| Data demonstrates improved patient survival associated with testing | ✔ | x |
| GEP Test | True Negative: False Negative Ratio | False-Negative Rate | Reference |
|---|---|---|---|
| CP-GEP | |||
| T1-T2 | 12:1 | 7.9% | Mulder, et al. 2020 |
| T1-T2 | 27:1 | 3.5% | Johansson, et al. 2021 |
| T1-T2 | 15:1 | 6.3% | Yousaf, et al. 2021 |
| T1-T2 | 27:1 | 3.5% | Stassen, et al. 2023 |
| T1-T2 | 14:1 | 6.8% | Sondak, et al. 2024 |
| CP-GEP T1-T2 Overall | 15:1 | 6.2% | |
| 31-GEP/ i31-SLNB | |||
| T1-T2 (31-GEP) | 34:1 | 3.0% | Yamamoto, et al. 2023 |
| T1-T2 (i31-SLNB)b | 25:1 | 3.9% | Whitman, et al. 2021 |
| T1-T2 (i31-SLNB) | 30:0 | 0% | Kriza, et al. 2024 |
| T1-T2a (i31-SLNB) | 58:0 | 0% | Beard, et al. 2024 |
| 31-GEP/ i31-SLNB T1-T2 Overall | 34:1 | 2.8% |
| Study | Design | Results | 3-year follow-up | 5-year follow-up |
|---|---|---|---|---|
| Onken et al., 2012. Ophthalmology (COOG) | Prospective multi-center, n=446 | Class 1A Class 1B Class 2 | 3-Year MFS | 5-Year MFS |
| Chappell et al., 2012. Amer J Ophthalmol. | Retrospective single-center, n=197 | Class 1 Class 2 | 5-Year DSS | |
| Correa & Augsburger, 2016. Am J Ophthalmol. | Prospective single-center n=299 | Class 1 Class 2 | 5-Year MFS | |
| Plasseraud et al., 2016. J Oncol. | Prospective multi-center, n=70 | Class 1 Class 2 | 3-Year MFS | |
| Demirci et al., 2018. Am J Ophthalmol. | Prospective single-center, n=293 | Class 1A Class 1B Class 2 | 3-Year MFS | |
| Aaberg et al., 2020. Ocul Oncol Pathol. | Prospective multi-center, n=89 | Class 1A Class 1B Class 2 | 5-Year MFS | |
| Binkley et al., 2020. Ophthalmol Retina. | Retrospective, 2-center, n=215 | Class 1 Class 2 | 3-Year MFS | 5-Year MFS |
| Wong et al., 2022. J Contemp Brachytherapy | Retrospective, single-center, n=180 | Class 1A Class 1B Class 2 | 5-Year MFS | |
| Singh et al., 2022. JAMA Ophthalmol. | Retrospective, 2-center n=347 | Class 1 Class 2 | 3 -Year MFS | 5-Year MFS |