High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness

Cancer Med. 2016 Jun;5(6):1022-30. doi: 10.1002/cam4.661. Epub 2016 Mar 6.

Abstract

Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti-PS100, anti-SOX10, anti-CD10, and anti-TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow-up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs.

Keywords: Circulating tumor cells; Metastatic melanoma; circulating tumor microemboli; immunocytochemistry; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Biopsy
  • Disease Progression
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / mortality
  • Melanoma / pathology*
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Neprilysin / genetics
  • Neprilysin / metabolism*
  • Phenotype
  • Prognosis
  • Proportional Hazards Models
  • SOXE Transcription Factors / genetics
  • SOXE Transcription Factors / metabolism*
  • Telomeric Repeat Binding Protein 2 / genetics
  • Telomeric Repeat Binding Protein 2 / metabolism*
  • Young Adult

Substances

  • Biomarkers
  • SOX10 protein, human
  • SOXE Transcription Factors
  • Telomeric Repeat Binding Protein 2
  • Neprilysin