227P - Circulating melanoma cells (CMCs) in mucosal and uveal melanomas

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Melanoma and other Skin Tumours
Translational Research
Presenter Leila Khoja
Authors L.T. Khoja1, P. Shenjere2, S. Bramley3, R. Milner4, A. Kvist4, R. Califano5, G. Clack6, A. Hughes6, P. Lorigan7, C. Dive3
  • 1The Paterson Institute for Cancer Research, Manchester/UK
  • 2Pathology, The Christie NHS Foundation Trust, M20 - 4BX/UK
  • 3Clinical And Experimental Pharmacology, The Paterson Institute for Cancer Research, M20 - 4BX/UK
  • 4Innovative Medicines, AstraZeneca Pharmaceuticals, SK10 - 4TG/UK
  • 5Department Of Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/UK
  • 6Early Phase Oncology, AstraZeneca Pharmaceuticals, SK10 - 4TG/UK
  • 7Medical Oncology, The Christie NHS Foundation Trust, M20 4BX - Manchester/UK

Abstract

Background

Melanoma subtypes are increasingly defined by genetic alterations (BRAF mutations in 50% and NRAS in 20% of cutaneous, c-Kit aberrations in acral and mucosal and GNA11 mutations in uveal melanomas. Targeted therapies such as vemurafenib in cutaneous and imatinib in mucosal melanomas have emerged. CMCs are a potential biomarker to assess response to treatment, monitor disease relapse and provide new targets for drug development. Molecular characterisation of CMCs may provide utility as a predictive biomarker to drug treatment.

Methods

The CellSearch marker dependent platform (Veridex, USA) enriches for CMCs utilising Melcam antibody for CMC capture and High Molecular Weight Melanoma associated Antigen (HMW-MAA) antibody for CMC detection. MART-1 was used as an additional CMC kit detection marker. The ISET marker independent platform (Isolation by Cell Size, Rarecells, France) enriches for CMCs based on cell size. Immunohistochemistry with CD45 and CD144 (leukocyte and endothelial cell markers) and S100 (melanoma marker) was performed to identify CMC characteristic staining and morphology.

Results

Twenty-three patients with metastatic disease were recruited prospectively (mucosal n = 13, uveal n = 10). CellSearch detected CMCs in 6/11mucosal (range 0-125, mean 21 median 1) and 7/10 uveal (range 0-510, mean 57 median 3) melanomas. MART-1 positive CMCs were detected in both subtypes but circulating tumour microemboli (CTM) were found only in mucosal melanomas. ISET detected CMCs in 10/12 mucosal (range 0-26, mean 4 median 2) and 7/10 uveal (range 0-19, mean 7 median 3) melanomas. CMCs were both S100+ and S100-. No CTM were detected by ISET. Comparison of the platforms in 20 patients (n = 10 of each mucosal and uveal melanomas) revealed variability in CMC detection between platforms (Spearman's correlation p = 0.17).

Conclusions

This is the first report of CMC detection by CellSearch in mucosal and uveal melanomas. Comparison with ISET revealed no relationship between numbers of CMCs detected in the same patients by each platform thus indicating significant CMC heterogeneity in CMC marker expression and size. Circulating tumour microemboli may indicate collective cell migration thus probing the biology of metastases formation.

Disclosure

G. Clack: Ownes stocks in Astra-Zeneca pharmaceuticals.

A. Hughes: ownes shares in Astra-Zeneca pharmaceuticals.

All other authors have declared no conflicts of interest.