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Dominique Vitoux, PharmD, PhD*; Samia Mourah, PharmD, PhD*; Delphine Kerob, MD; Olivier Verola, MD; Nicole Basset-Seguin, MD, PhD; Michel Baccard, MD; Noel Schartz, MD, PhD; Laurence Ollivaud, MD; Alain Archimbaud, MD; Jean-Marie Servant, MD; Marc Revol, MD; Marie-Elisabeth Toubert, MD; Marie-Pierre Podgorniak; François Plassa, PhD; Raphael Porcher, PhD; Céleste Lebbé, MD, PhD

Arch Dermatol. 2009;145(10):1105-1113.

Objectives  To evaluate the prognostic value of melanocytic differentiation antigens and angiogenesis biomarkers in sentinel lymph nodes (SLNs) with melanoma micrometastases.

Design  Prognostic study of an inception cohort.

Setting  Academic research.

Patients  Between July 1, 1999, and July 31, 2002, all patients who had primary cutaneous or mucosal melanomas that have a Breslow depth of 1.5 mm or greater, ulceration, or Clark level IV or V, or had SLN biopsies.

Main Outcome Measures  By the use of quantitative reverse transcription–polymerase chain reaction, the expression of the following was analyzed in SLNs: 2 melanocytic differentiation antigens (tyrosinase [P17646] and melanoma antigen recognized by T cells [MART-1; Q16655]) and genes involved in angiogenesis (VEGF [NM_001025366] and VEGFR2 [AF035121]), lymphangiogenesis (VEGFC [NM_005429], VEGFR3 [X68203], LYVE1 [NM_016164], and PROX1 [002763]), and invasion (uPA [NM_002658], PAI1 [NM_00602], and EMMPRIN [L10240]). Outcome measures were the association of these melanocytic differentiation antigens and angiogenesis biomarkers with clinicopathologic characteristics of patients, and an evaluation of the prognostic value for relapse-free survival and overall survival.

Results  Ninety-one patients were included, with a median follow-up period of 41 months. Micrometastases were present in 15% (14 of 91) of patients. Tyrosinase (P < .001), MART-1 (P < .001), vascular endothelial growth factor 121 (VEGF₁₂₁) (P = .007), and PAI1 (P = .02) expression was significantly associated with micrometastasis. In univariate analysis, histologic findings and tyrosinase and MART-1 expression were significantly associated with relapse-free survival. Tyrosinase and MART-1 expression was associated with overall survival. A multiple Cox proportional hazards regression model identified negative histologic findings and tyrosinase expression that exceeded 27 copies/copy of TATA box-binding protein (third quartile) as significantly associated with an increased risk of relapse or death.

Conclusions  Quantitative assessment of melanocytic differentiation antigens in SLNs, which has prognostic value, is more specific than qualitative assessment. Prognosis may be more effectively predicted by the combination of quantitative assessment of melanocytic differentiation antigens in SLNs with histologic assessment. A significant association was found between the presence of micrometastases and the expression of angiogenesis biomarkers.

Author Affiliations: Pharmacology Laboratory (Dr Mourah and Ms Podgorniak), Unité Fonctionnelle Diagnostic Biologique Automatise, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7151 (Drs Vitoux and Plassa), and Departments of Dermatology (Drs Kerob, Basset-Seguin, Baccard, Schartz, Ollivaud, Archimbaud, and Lebbé), Pathology (Dr Verola), Plastic Surgery (Drs Servant and Revol), Nuclear Medicine (Dr Toubert), and Biostatistics and Medical Informatics (Dr Porcher), Institut Universitaire d’Hématologie, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Université Paris 7, Institut National de la Santé et de la Récherche Médicale Unités 716 et 717, Paris, France.
* Indicates co–first authorship.

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