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Pablo Zoroquiain, Jose Joao Mansure, Ciro Garcia, Maria Antonia Saornil, William April, Miguel N Burnier; Characterization and prognostic significance and of small epithelioid cell populations in uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3954.
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© ARVO (1962-2015); The Authors (2016-present)
Uveal melanoma (UM) is a malignant neoplasia that arises from uveal melanocytes. Despite the availability of various treatment modalities, approximately 40% of patients develop metastases, 90% of which will succumb to their disease. UM is composed of two main type of cells: spindle and epithelioid. However, there is a subset of neoplastic small epithelioid cells that are located predominately in the infiltrative tumor margins or surrounding blood vessels. The aim of this study is to characterize and evaluate the correlation between the presence of these small epithelioid cells and clinical outcome.
The clinical-pathological features of 70 UM patients were evaluated. The presence of small epithelioid cells was quantified based on percentage of tumor volume. Furthermore, in a subset of cases (n=6) the small epithelioid cells were characterized using melanocytic markers (HMB-45, Melan A and SOX-10), stem cell markers (CD133, CD24 and CD38) and T cell lymphocytes (CD3). Univariate and multivariate analyses were conducted to evaluate survival. Clinical follow up was available for all patients (mean 148.6 months; SEM 15.1)
Results: The ratio of small epithelioid cell components of all 70 tumors ranged from 0% to 30% (median, 1%). Thirty-nine tumors (55.7%) had areas with small epithelioid cells. Univariate analysis showed that mixed versus spindle cell (P=0.006), higher lymphocytic infiltration (P=0.04), macrophage infiltration (P=0.02), ciliary body involvement (P=0.02) and >5% of small epithelioid cell component (P<0.0001) had a significant negative impact on metastasis-free survival. Small epithelioid cell component >5% was present in 24 cases (34.3%). Of these, three were classified as spindle and 21 were mixed. Multivariate analysis revealed that a >5% small cell component was the most significant morphological adverse prognostic factor (P<0.001, HR=4.98). Moreover, the small epithelioid cells were negative for HMB45, focally and weakly positive for MELAN A and SOX10, and were negative for stem cell markers and CD3.
A high small epithelioid cell component is a strong negative prognostic indicator in patients with UM. This feature might be useful to prognosticate enucleated patients when molecular studies are not available. Further characterization may lead to new therapeutic targets and a better understanding of the metastatic process in UM.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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