Molecular and immunohistochemical analyses of uveal melanoma patient cohort

Hc, Sarubi; Pereira, Núbia Braga; Gomes, Ciro Martins; Gomez, Ricardo Santiago; Acm, Carmo; Fm, Melo; Bastos‐Rodrigues, Luciana; Ms, Pedrosa; Friedman, Eitan; L, De Marco

doi:10.1097/cmr.0000000000000523

Cited by 6 publications

(5 citation statements)

References 25 publications

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“…BRCA2 protein staining was mainly observed in the cytoplasm of EP cells. This may be attributed to a novel role in the motility and migration of cancer cells that were proposed for cytoplasmic and membranous localised BRCA1 and BRCA2 proteins [ 62 , 63 ].…”

Section: Discussionmentioning

confidence: 99%

“…Here, previous studies have proposed that germline variants in the genes BRCA1 and BRCA2 may represent predisposing factors. However, this currently remains controversial [ 61 , 62 ]. In particular, it remains unclear whether the BRCA and HRR pathway is associated with melanoma subtypes in general, i.e., cutaneous, uveal, acral, and mucosal, or whether each melanoma subtype has a distinct aetiology.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, it remains unclear whether the BRCA and HRR pathway is associated with melanoma subtypes in general, i.e., cutaneous, uveal, acral, and mucosal, or whether each melanoma subtype has a distinct aetiology. Previous studies found that the p53 and BRCA pathways played a key role in uveal melanoma patients with a poor prognosis [ 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

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Whole-exome sequencing in eccrine porocarcinoma indicates promising therapeutic strategies

et al. 2021

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Malignant sweat gland tumours are rare, with the most common form being Eccrine porocarcinoma (EP). To investigate the mutational landscape of EP, we performed whole-exome sequencing (WES) on 14 formalin-fixed paraffin-embedded samples of matched primary EP and healthy surrounding tissue. Mutational profiling revealed a high overall median mutation rate. This was attributed to signatures of mutational processes related to ultraviolet (UV) exposure, APOBEC enzyme dysregulation, and defective homologous double-strand break repair. All of these processes cause genomic instability and are implicated in carcinogenesis. Recurrent driving somatic alterations were detected in the EP candidate drivers TP53, FAT2, CACNA1S, and KMT2D. The analyses also identified copy number alterations and recurrent gains and losses in several chromosomal regions including that containing BRCA2, as well as deleterious alterations in multiple HRR components. In accordance with this reduced or even a complete loss of BRCA2 protein expression was detected in 50% of the investigated EP tumours. Our results implicate crucial oncogenic driver pathways and suggest that defective homologous double-strand break repair and the p53 pathway are involved in EP aetiology. Targeting of the p53 axis and PARP inhibition, and/or immunotherapy may represent promising treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Whole-exome sequencing in eccrine porocarcinoma indicates promising therapeutic strategies

et al. 2021

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“…Moreover, recent findings reported that the microenvironment influences the expression of inhibitory immune checkpoints. 8 , 29 , 39 Finally, concerning the recent genetic landscape, mutations in GNAQ are frequently observed in primary UM. BAP1 and SF3B1 mutations are found most frequently in metastatic disease, whereas EIF1AX gene mutation is related to a favorable prognosis.…”

Section: Discussionmentioning

confidence: 99%

Expression of GNAQ, BAP1, SF3B1, and EIF1AX Proteins in the Aqueous Humor of Eyes Affected by Uveal Melanoma

Midena,

Parrozzani,

Frizziero

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Purpose The purpose of this study was to quantify specific aqueous humor (AH) proteins in eyes affected by posterior uveal melanoma (UM). Methods Thirty-six eyes affected by primary UM were included. Tumor thickness and largest basal diameter were specific clinical characteristics. Tumors were staged with the American Joint Commission on Cancer Eighth Edition (AJCC) classification. During the brachytherapy (Iodine-125) surgical procedure, both the AH sample collection and the 25-gauge transscleral fine needle aspiration biopsy (FNAB) were performed. AH samples were analyzed by immunoprecipitation and SDS PAGE techniques to quantify GNAQ, BAP1, SF3B1, and EIF1AX proteins. Cytologic material underwent fluorescence in situ hybridization for chromosome 3. The AH of 36 healthy eyes was used as the control group. Cluster analysis of groups was also performed. Results Compared with the control group, significantly higher protein levels of: GNAQ ( P = 0.02), BAP1 ( P = 0.01), and SF3B1 ( P = 0.02) were detected in eyes with UM. Cluster analysis of UM group revealed 2 clusters, one showing higher expression of GNAQ and BAP1 protein and one of EIF1AX protein. Moreover, the 2 clusters corresponded with the chromosome 3 status of UM. Conclusions Specific and selected proteins may be detected in the AH of eyes affected by UM. These findings confirm the possibilities provided by AH analysis in UM.

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“…Eye-confined disease is treated either by vision-saving therapies such as brachytherapy and proton beam radiotherapy or by enucleation [ 7 , 8 ]. Despite recent improvements in tumor local control, UMs have a high propensity to metastasize [ 2 , 9 , 10 ]. Approximately 50% of patients develop metastases within 10 years from the diagnosis, and the survival rates of patients with metastatic disease remain poor [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Digital Quantification of Intratumoral CD8+ T-Cells Predicts Relapse and Unfavorable Outcome in Uveal Melanoma

Hurdogan

Logu

Galli

et al. 2022

Cancers

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Although it is a disease that occurs mainly in the Caucasian population, uveal melanoma (UM) is the most common primary intraocular tumor in adults. Here, we used digital pathology and image analysis for the diagnosis of UM and the prediction of the prognosis. Our retrospective study included a total of 404 histopathological slides from 101 patients. A digital image acquisition and quantitative analysis of tissue immune biomarkers (CD4, CD8, CD68, CD163) were performed. A negative impact of the intratumoral CD8 positive cell density higher than 13.3 cells/mm2 was detected for both RFS (HR 2.08, 95% Cl 1.09 to 3.99, p = 0.027) and OS (HR 3.30, 95% CI 1.58 to 6.88, p = 0.001). Moreover, we confirmed that older age and stage III were independent negative prognostic factors for both RFS and OS. Our results suggest that a specific distribution profile of CD8 in UM might predict the risk of relapse and death, with potential implications for determining which subgroups of UMs are amenable to specific pharmacological treatment regimens.

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Molecular and immunohistochemical analyses of uveal melanoma patient cohort

Cited by 6 publications

References 25 publications

Whole-exome sequencing in eccrine porocarcinoma indicates promising therapeutic strategies

Whole-exome sequencing in eccrine porocarcinoma indicates promising therapeutic strategies

Expression of GNAQ, BAP1, SF3B1, and EIF1AX Proteins in the Aqueous Humor of Eyes Affected by Uveal Melanoma

Digital Quantification of Intratumoral CD8+ T-Cells Predicts Relapse and Unfavorable Outcome in Uveal Melanoma

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