title: 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.
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.
authors.affiliation: Institute for Research on Cancer and Aging in Nice (IRCAN) INSERM U1081/CNRS UMR7284, University of Nice Sophia Antipolis, Antoine Lacassagne Cancer Center, Nice, France.|Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Long
authors.affiliation: Institute for Research on Cancer and Aging in Nice (IRCAN) INSERM U1081/CNRS UMR7284, University of Nice Sophia Antipolis, Antoine Lacassagne Cancer Center, Nice, France.|Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.|Human Biobank, Pasteur Hospital, BB-0033-00025, Nice, France.
authors.forename: Marius
authors.initials: M
authors.lastname: Ilie
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
authors.forename: Coraline
authors.initials: C
authors.lastname: Bence
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Butori
authors.affiliation: Human Biobank, Pasteur Hospital, BB-0033-00025, Nice, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Selva
authors.affiliation: Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.
authors.forename: Salomé
authors.initials: S
authors.lastname: Lalvée
authors.affiliation: Human Biobank, Pasteur Hospital, BB-0033-00025, Nice, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Bonnetaud
authors.affiliation: Department of Surgery, Comprehensive Cancer Center, Antoine Lacassagne, Nice, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Poissonnet
authors.affiliation: Department of Dermatology, Archet II Hospital, Nice, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lacour
authors.affiliation: Department of Dermatology, Archet II Hospital, Nice, France.|INSERM U1065 Team 1, University of Nice Sophia Antipolis, Equipe Labellisée Ligue 2013, Nice, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bahadoran
authors.affiliation: Institute for Research on Cancer and Aging in Nice (IRCAN) INSERM U1081/CNRS UMR7284, University of Nice Sophia Antipolis, Antoine Lacassagne Cancer Center, Nice, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Brest
authors.affiliation: Institute for Research on Cancer and Aging in Nice (IRCAN) INSERM U1081/CNRS UMR7284, University of Nice Sophia Antipolis, Antoine Lacassagne Cancer Center, Nice, France.|Unit of Genetics, Archet Hospital, Nice, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.affiliation: INSERM U1065 Team 1, University of Nice Sophia Antipolis, Equipe Labellisée Ligue 2013, Nice, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Ballotti
authors.affiliation: Institute for Research on Cancer and Aging in Nice (IRCAN) INSERM U1081/CNRS UMR7284, University of Nice Sophia Antipolis, Antoine Lacassagne Cancer Center, Nice, France.|Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.|Human Biobank, Pasteur Hospital, BB-0033-00025, Nice, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Hofman
authors.affiliation: Institute for Research on Cancer and Aging in Nice (IRCAN) INSERM U1081/CNRS UMR7284, University of Nice Sophia Antipolis, Antoine Lacassagne Cancer Center, Nice, France.|Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France.|Human Biobank, Pasteur Hospital, BB-0033-00025, Nice, France.|Cancer Research Association (ARC) Labelled Team, Villejuif, France.|"OncoAge" Hospital-University Federation, CHU Nice, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001706:Biopsy; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D035341:Telomeric Repeat Binding Protein 2; D015260:Neprilysin
keywords: Circulating tumor cells; Metastatic melanoma; circulating tumor microemboli; immunocytochemistry; prognosis