Poster Presentation 28th Lorne Cancer Conference 2016

Evaluation of Melanocytic, Melanoma, and Stem Cell Marker Expression in Primary Uveal Melanoma for the Improvement of Immunomagnetic Circulating Tumour Cell Capture (#116)

Aaron Beasley 1 , Tersia L Vermeulen 2 , Leslie Calapre 1 , Bob Mirzai 3 , Melanie R Ziman 1 , Elin S Gray 1
  1. School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia
  2. Anatomical Pathology, PathWest, Perth, WA, Australia
  3. School of Pathology and Laboratory Medicine, The University of Western Australia, Crawley, WA, Australia

Uveal melanoma (UM) although a rare disease, it is the most common intraocular disease in adults1. Metastatic disease develops in 50% of patients, which is strongly predicted by specific cytogenetic features2. Unfortunately, current methods to for genetic analysis require biopsy of the eye, which harbours the risk of serious complications3. As UM metastasises by haematogenous dissemination4, circulating tumour cells (CTCs) may offer a safer and quicker alternative to biopsy. However, the rate of capture of CTCs by targeting a single molecule (CSPG4) is around 50%. We hypothesise that multiple marker capture will improve CTC detection allowing the implementation of a liquid biopsy for UM.

            Here we aimed to evaluate the expression several melanocytic, melanoma, and stem cell markers on UM tumours. A tissue microarray was prepared from 10 archived primary UMs, in duplicate, and stained with 7 markers by IHC and cores were scored based on intensity as negative (0), weak positive (1), moderate positive (2), and strong positive (3).

           CD271, a cutaneous melanoma stem cell marker, was not expressed in these tumours.  MART1 and gp100 were expressed in all tumours, with an average intensity of 2.4 ± 0.6 and 1.5 ± 0.4 respectively. Meanwhile, S100 and MCAM were expressed in 70% (1.5 ± 0.5) and 40% (1.6 ± 0.5) of patients respectively. In addition, less characterised markers for UM such as 5-HT2B and RANK were expressed in 60% (1.0 ± 0.2) and 50% (1.3 ± 0.4) of the tumours. Interestingly, in the two tumour samples with spindle cell phenotype, a cell type associated with improved prognosis, both 5-HT2B and MCAM were not present. 5-HT2B is upregulated in tumours with a poor prognosis, and MCAM has been implicated in the metastatic propensity of UM.

          Combined with clinical, histopathological, and genotypic data, this data will aid the design a marker panel that would encapsulate numerous phenotypic variants of UM, in efforts to capture CTCs from all patients.

  1. Jovanovic, P., M. Mihajlovic, J. Djordjevic-Jocic, S. Vlajkovic, S. Cekic, and V. Stefanovic. 2013. Ocular melanoma: an overview of the current status. International Journal of Clinical and Experimental Pathology 6:1230-1244.
  2. Harbour, J.W., and D.L. Chao. 2014. A molecular revolution in uveal melanoma: implications for patient care and targeted therapy. Ophthalmology 121:1281-1288.
  3. Pereira, P.R., A.N. Odashiro, L.A. Lim, C. Miyamoto, P.L. Blanco, M. Odashiro, S. Maloney, D.F. De Souza, and M.N. Burnier, Jr. 2013. Current and emerging treatment options for uveal melanoma. Journal of Clinical Ophthalmology 7:1669-1682.
  4. Tulley, P.N., M. Neale, D. Jackson, J.S. Chana, R. Grover, I. Cree, A.O. Grobbelaar, and G.D. Wilson. 2004. The relation between c-myc expression and interferon sensitivity in uveal melanoma. British Journal of Ophthalmology 88:1563-1567.