Conjunctival melanoma: pitfalls and dilemmas in management

Shildkrot, Yevgeniy; Wilson, Matthew W.

doi:10.1097/icu.0b013e32833b7aab

Cited by 49 publications

(56 citation statements)

References 59 publications

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“…It occurs more commonly in Caucasian populations and in middleaged and elderly individuals (13). The rate of local recurrence is high, between 26%-61% at 5 years and 38%-69% at 10 years (15)(16)(17)(18)(19) after diagnosis. Disease-related mortality at 10 years ranges from 13% to 38% (15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Conjunctival Melanomas Harbor BRAF and NRAS Mutations and Copy Number Changes Similar to Cutaneous and Mucosal Melanomas

Griewank

Westekemper

Murali

et al. 2013

Clinical Cancer Research

189

187

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Purpose: Conjunctival melanoma is a rare but potentially deadly tumor of the eye. Despite effective local therapies, recurrence and metastasis remain frequent. Once the tumor has metastasized, treatment options are limited and the prognosis is poor. To date, little is known of the genetic alterations in conjunctival melanomas.Experimental Design: We conducted genetic analysis of 78 conjunctival melanomas, to our knowledge the largest cohort reported to date. An oncogene hotspot array was run on 38 samples, screening for a panel of known cancer-relevant mutations. Thirty tumors were analyzed for genome-wide copy number alterations (CNA) using array-based comparative genomic hybridization. Sanger sequencing of selected target mutations was conducted in all samples.Results: BRAF mutations were identified in 23 of 78 (29%) tumors. NRAS mutations, previously not recognized as relevant in conjunctival melanoma, were detected in 14 of 78 (18%) tumors. We found CNAs affecting various chromosomes distributed across the genome in a pattern reminiscent of cutaneous and mucosal melanoma but differing markedly from uveal melanoma.Conclusions: The presence of NRAS or BRAF mutations in a mutually exclusive pattern in roughly half (47%) of conjunctival melanomas and the pattern of CNAs argue for conjunctival melanoma being closely related to cutaneous and mucosal melanoma but entirely distinct from uveal melanoma. Patients with metastatic conjunctival melanoma should be considered for therapeutic modalities available for metastatic cutaneous and mucosal melanoma including clinical trials of novel agents.

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Section: Introductionmentioning

confidence: 99%

Conjunctival Melanomas Harbor BRAF and NRAS Mutations and Copy Number Changes Similar to Cutaneous and Mucosal Melanomas

Griewank

Westekemper

Murali

et al. 2013

Clinical Cancer Research

189

187

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“…[6][7][8] Furthermore, the mortality rate is high, ranging from 13% to 38% after 10 years. [9][10][11] In this malignancy, essential mutations occur in the B-RAF and N-RAS genes.…”

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confidence: 99%

Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma

Pontes

Groenewoud

Cao

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Pontes KCS, Groenewoud A, Cao J, Ataide LMS, Snaar-Jagalska E, Jager MJ. Evaluation of (fli:GFP) Casper zebrafish embryos as a model for human conjunctival melanoma. Invest Ophthalmol Vis Sci. 2017;58:6065-6071. DOI:10.1167/iovs.17-22023 PURPOSE. Conjunctival melanoma (CM) is a rare malignant disease that can lead to recurrences and metastases. There is a lack of effective treatments for the metastases, and we set out to develop a new animal model to test potential therapies. Zebrafish are being used as a model for many diseases, and our goal was to test whether this animal could be used to study CM. METHODS.Three human CM cell lines (CRMM-1 and CM2005.1, which both harbor a B-RAF mutation, and CRMM-2, which has an N-RAS mutation) were injected into the yolk sac, around the eye, and into the duct of Cuvier of transgenic (fli:GFP) Casper zebrafish embryos. Fluorescent and confocal images were taken to assess the phenotype and the behavior of engrafted cells and to test the effect of Vemurafenib as a treatment against CM.RESULTS. While the cells that had been injected inside the yolk sac died and those injected around the eye sporadically went into the circulation, the cells that had been injected into the duct of Cuvier colonized the zebrafish: cells from all three cell lines proliferated and disseminated to the eyes, where they formed clusters, and to the tail, where we noticed extravasation and micrometastases. Vemurafenib, a potent agent for treatment of B-RAF V600E-positive melanoma, inhibited outgrowth of CRMM-1 and CM2005.1 cells in a mutation-dependent way.CONCLUSIONS. The (fli:GFP) Casper zebrafish embryo can be used as an efficient animal model to study metastatic behavior of human CM cells and warrants further testing of drug efficacy to aid care of CM patients.

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“…These findings raise the case against the indiscriminate use of orbital exenteration, which could be reserved for T4 and selected T3 cases, since no real improvement in survival is obtained with this procedure. However, recently, other studies have found greater significance for multi-focality and status of surgical margins, which may require surgery that is more extensive and/or radiotherapy to achieve local control (16) . Therefore, our results show that the use of chemotherapy alone or combined with radiotherapy appears to give a survival benefit to our patients (not extensively analyzed because of the small number of patients of our series) and it helps to plan the surgical treatment with a less invasive approach.…”

Section: Discussionmentioning

confidence: 99%