Transvitreal Retinochoroidal Biopsy Provides a Representative Sample From Choroidal Melanoma for Detection of...

To compare the status of chromosomes 3 and 8 in 25-gauge transvitreal retinochoroidal (TVRC) biopsy specimens and enucleated eyes in order to evaluate for genetic heterogeneity and the utility of TVRC biopsy to obtain an adequate sampling of the tumor.

Genetic heterogeneity was evaluated in 27 patients treated at Rigshospitalet between 2009 and 2013. The TVRC biopsy was performed to confirm diagnosis prior to enucleation and was subsequently analyzed using two techniques for chromosomes 1p, 3, 6, and 8: Fluorescence in situ hybridization (FISH) in all patients, and multiplex ligation-dependent probe amplification (MLPA) in 16 patients. Biopsies were compared with histological sections from matched enucleated eyes, which were microdissected following a hexagonal grid and analyzed with MLPA.

Twenty-four tumors were available for analysis. The TVRC biopsy identified chromosome 3 aberrations with MLPA in all cases (sensitivity = 100%), while FISH missed two cases (sensitivity = 89%). Conversely, FISH analysis demonstrated polyploidy of chromosome 3 in three additional cases missed by MLPA. Chromosome 8 aberrations were detected in 75% of cases with MLPA and 68% of cases with FISH. Heterogeneity of chromosomes 3 and 8 was shown in 3 (13%) and 11 tumors (46%), respectively, with an increased frequency of genetic aberrations toward the base of the tumor (P = 0.049). The study showed no difference in tumor size between heterogeneous and homogenous melanomas (P = 0.82).

Regardless of genetic heterogeneity, the TVRC biopsy identified all patients with a high risk of developing metastatic disease when a combination of chromosome 3 and 8 status was assessed.