Relationship between clinical features, GEP class, and PRAME expression in uveal melanoma

Schefler, Amy C; Koca, Emre; Bernicker, Eric H.; Corrêa, Zélia M.

doi:10.1007/s00417-019-04335-w

Cited by 29 publications

(15 citation statements)

References 19 publications

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“…In previous publications, PRAME expression in UM was found to be associated with increasing LBD and higher GEP class [10,11]. Curiously, nearly a third of Class 1A UM in one report were found to express PRAME, yet Class 1A tumors are reported to carry a low metastatic risk of 2% at 5 years.…”

Section: Discussionmentioning

confidence: 85%

“…Recently, expression of PRAME (Preferentially Expressed Antigen in Melanoma), a cancer-testis antigen, has been described as an independent biomarker for metastasis [9]. While PRAME-positive Class 1 UM patients might be at elevated risk for metastasis, PRAME positivity might correlate with a shorter time to metastasis in Class 2 UM patients [10,11].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Metastatic Risk Factors Associated with Class 1A Uveal Melanoma Patients

Ballhausen

Urias

Gruschkus

et al. 2021

Cancers

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In uveal melanoma (UM), gene expression profiling (GEP) is commonly used to classify metastatic risk into three groups (Class 1A, 1B, and 2). Class 1A patients have a lower metastatic risk of 2% at 5 years compared to other groups. We aimed to describe clinical features associated with the development of metastasis in this low-risk group. This single-center IRB-approved retrospective case series review included all UM patients between February 2006 and March 2019 with an archived or fresh specimen classified as Class 1A. Cox regression and receiver operating characteristics analyses were used to identify factors associated with metastasis development and OS. Among 73 UM patients with Class 1A, the 5-year cumulative incidence of local recurrence and distant metastasis was 4.2% and 17.0%, respectively. Stage III disease (HR 20.7; 95% confidence interval (95% CI) 1.4–300.6; p = 0.0264) was found to be independently associated with metastatic recurrence, while primary therapy was associated with OS (enucleation vs. brachytherapy, HR 13.5; 95% CI 1.3–147.6; p = 0.0348). Combined clinical decision-making utilizing factors such as GEP class, American Joint Committee on Cancer (AJCC) stage, and COMS size could have a significant clinical impact by improving risk stratification and adapting follow-up intervals in UM Class 1A patients.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Metastatic Risk Factors Associated with Class 1A Uveal Melanoma Patients

Ballhausen

Urias

Gruschkus

et al. 2021

Cancers

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“…It has been reported that PRAME is highly overexpressed in melanoma tumour samples and that PRAME is considered an immunotherapy target for the treatment of melanoma . PRAME‐positive status is significantly correlated with the largest basal diameter (LBD), tumour volume and worsening gene expression profiling (GEP) class in uveal melanoma (UM) . Two studies confirmed that PRAME is significantly associated with an increased risk of metastasis in uveal melanomas .…”

Section: Role Of Prame In Cancersmentioning

confidence: 98%

The role of the cancer testis antigen PRAME in tumorigenesis and immunotherapy in human cancer

Zou

Wang

et al. 2020

Cell Proliferation

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Preferentially expressed antigen in melanoma (PRAME), which belongs to the cancer/testis antigen (CTA) gene family, plays a pivotal role in multiple cellular processes and immunotherapy response in human cancers. PRAME is highly expressed in different types of cancers and is involved in cell proliferation, apoptosis, differentiation and metastasis as well as the outcomes of patients with cancer. In this review article, we discuss the potential roles and physiological functions of PRAME in various types of cancers. Moreover, this review highlights immunotherapeutic strategies that target PRAME in human malignancies. Therefore, the modulation of PRAME might be useful for the treatment of patients with cancer.

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“…Furthermore, the increased expression of PRAME is a marker of poor prognosis in different types of neoplasias, namely, breast cancer [ 131 ], head and neck squamous cell carcinoma (HNSCC) [ 132 ], neuroblastoma [ 133 ], osteosarcoma [ 134 ], among others. The prognostic significance of PRAME expression in UM emerged from a few studies conducted over the past 5 years, which showed that PRAME expression in UM is associated with an increased tumour volume, enhanced metastatic risk and global inferior prognosis [ 103 , 104 , 105 , 106 ].…”

Section: Current Well-established Prognostic Biomarkers In Uveal Melanomamentioning

confidence: 99%

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

Lamas

Martel

Nahon-Estève

et al. 2021

Cancers

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Uveal melanoma (UM) is the most common malignant intraocular tumour in the adult population. It is a rare cancer with an incidence of nearly five cases per million inhabitants per year, which develops from the uncontrolled proliferation of melanocytes in the choroid (≈90%), ciliary body (≈6%) or iris (≈4%). Patients initially present either with symptoms like blurred vision or photopsia, or without symptoms, with the tumour being detected in routine eye exams. Over the course of the disease, metastases, which are initially dormant, develop in nearly 50% of patients, preferentially in the liver. Despite decades of intensive research, the only approach proven to mildly control disease spread are early treatments directed to ablate liver metastases, such as surgical excision or chemoembolization. However, most patients have a limited life expectancy once metastases are detected, since there are limited therapeutic approaches for the metastatic disease, including immunotherapy, which unlike in cutaneous melanoma, has been mostly ineffective for UM patients. Therefore, in order to offer the best care possible to these patients, there is an urgent need to find robust models that can accurately predict the prognosis of UM, as well as therapeutic strategies that effectively block and/or limit the spread of the metastatic disease. Here, we initially summarized the current knowledge about UM by compiling the most relevant epidemiological, clinical, pathological and molecular data. Then, we revisited the most important prognostic factors currently used for the evaluation and follow-up of primary UM cases. Afterwards, we addressed emerging prognostic biomarkers in UM, by comprehensively reviewing gene signatures, immunohistochemistry-based markers and proteomic markers resulting from research studies conducted over the past three years. Finally, we discussed the current hurdles in the field and anticipated the future challenges and novel avenues of research in UM.

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Relationship between clinical features, GEP class, and PRAME expression in uveal melanoma

Cited by 29 publications

References 19 publications

Metastatic Risk Factors Associated with Class 1A Uveal Melanoma Patients

Metastatic Risk Factors Associated with Class 1A Uveal Melanoma Patients

The role of the cancer testis antigen PRAME in tumorigenesis and immunotherapy in human cancer

Prognostic Biomarkers in Uveal Melanoma: The Status Quo, Recent Advances and Future Directions

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