Uveal Melanoma Cell Lines: Where do they come from? (An American Ophthalmological Society Thesis)

Abstract

Purpose: To determine whether some of the most often used uveal melanoma cell lines resemble their original tumor.

Methods: Analysis of the literature, patient charts, histopathology, mutations, chromosome status, HLA type, and expression of melanocyte markers on cell lines and their primary tumors. We examined five cell lines and the primary tumors from which they were derived.

Results: Four of the five examined primary tumors were unusual: one occupied the orbit, two were recurrences after prior irradiation, and one developed in an eye with a nevus of Ota. One cell line did not contain the GNA11 mutation, but it was present in the primary tumor. Three of the primary tumors had monosomy 3 (two of these lacked BAP1 expression); however, all five cell lines showed disomy 3 and BAP1 expression. All of the cell lines had gain of 8q. Two cell lines lacked expression of melanocyte markers, although these were present in the corresponding primary tumor.

Conclusions: All cell lines could be traced back to their original uveal melanoma. Four of the five primary tumors were unusual. Cell lines often differed from their primary tumor in chromosome status and melanocyte markers. However, their specific chromosome aberrations and capacity to continue proliferation characterize them as uveal melanoma cell lines.

FIGURE 1

Clinical photographs of the eye and the choroidal melanoma that had been treated with an iodine-125 plaque in August 1988 and after enucleation gave rise to cell line Mel202. Top row, fundus and choroidal melanoma at the time of diagnosis in July 1988. Middle row, fundus and choroidal melanoma in January 1989 (left) and in March 1989 (right). Bottom row, eye just prior to enucleation in 1990 (left) and histologic section of the scleral part of the tumor (right), illustrating the high density of blood vessels and pigment macrophages (hematoxylin-eosin, ×10).

FIGURE 2

Histologic overviews of three choroidal melanoma (hematoxylin-eosin, original magnification ×12.5), expression of Melan-A/MART-1, HMB45, and S100 (original magnification ×400) for tumors E-1268-94 (Mel270) (top), E-994-95 (Mel285) (middle), and 131-96 (Mel290) (bottom) (original magnification ×400). The morphology and immunophenotypic profile of the three tumors are consistent with choroidal melanoma. The aspect of the iris of 131-96 (lower left) is consistent with a nevus of Ota.