Comparative Cytogenetic Abnormalities in Paired Choroidal Melanoma Samples Obtained Before and After Proton Beam Irradiation by Transscleral Fine-Needle Aspiration Biopsy and Endoresection.

Alexandre Matet,Gaëlle Pierron,Livia Lumbroso-Le Rouic,Rémi Dendale,Christine Lévy-Gabriel,Sarah Tick,Manuel Rodrigues,Khadija Aït Raïs,Martina Angi,Nathalie Cassoux,Denis Malaise

doi:10.3390/cancers11081173

Abstract

This study compared the cytogenetic profiles of choroidal melanoma samples retrieved before and after proton beam irradiation. Twenty-four consecutive patients who underwent both fine-needle aspiration biopsy (FNAB) during tantalum clip positioning, and endoresection within three months of irradiation, were retrospectively included. Chromosome alterations were explored by array comparative genomic hybridization. Age at diagnosis was 50 ± 14 years, tumor thickness was 8.6 ± 1.7 mm and tumor diameter was 12.4 ± 2.3 mm. Six FNAB samples were non-contributive (25%), versus one endoresection sample (4%) (p = 0.049). Among 17 cases with paired contributive samples, the profiles of chromosomes 3 and 8 were identical in all cases, except one with partial chromosome 3 loss on the FNAB sample only. Three cases presented additional discordant aberrations on chromosomes other than 3 or 8q. Overall, we identified monosomy 3 in two cases, 8q gain in six cases, and both alterations in three cases. All cases presented GNAQ or GNA11 mutations assessed by a custom next-generation sequencing panel. Among the six cases with non-contributive initial FNAB, three cases presented abnormal 3 or 8q chromosomes detected on the endoresection material. These results demonstrate the higher rentability of endoresection material for cytogenetic analysis compared to FNAB, and provide clinical evidence of tumor heterogeneity in choroidal melanoma.

Highlights

Choroidal melanoma, the most frequent intraocular malignancy, leads to metastatic disease in approximately 50% of affected individuals [1]
The present study aims at comparing cytogenetic analyses performed on paired choroidal melanoma samples obtained by trans-scleral fine-needle aspiration biopsy and using endoresection material, obtained from single patients before and after proton beam irradiation, respectively
From January 2013 to December 2016, 1388 patients treated at our institution for choroidal melanoma were recorded into the institutional database

Summary

Introduction

The most frequent intraocular malignancy, leads to metastatic disease in approximately 50% of affected individuals [1]. While the primary tumor can be efficiently managed by either proton beam therapy, plaque brachytherapy, or enucleation for large tumors [2], there is, to date, no effective therapy providing long-term control of metastatic localizations [3,4,5,6]. Tumor material is retrieved whenever possible at diagnosis in order to determine the metastatic risk, to adapt the timing and modality of the oncological follow-up, and to detect early metastatic disease [18]. For large melanomas requiring primary enucleation, tumor material can be obtained from ocular specimens [10,11]. For small and middle-sized tumors eligible for conservative treatment, tumor material is retrieved by trans-scleral fine-needle aspiration biopsy at the time of tantalum clip positioning prior to irradiation [19], or by transvitreal biopsy performed before or after irradiation, according to local procedures [20]

Methods

Results

Conclusion