Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma

Research output: Contribution to journalJournal articleResearchpeer-review

  • Alexander Meves
  • Ekaterina Nikolova
  • Joel B Heim
  • Edwin J Squirewell
  • Mark A Cappel
  • Mark R Pittelkow
  • Clark C Otley
  • Nille Behrendt
  • Saunte, Ditte Marie
  • Jorgen Lock-Andersen
  • Louis A Schenck
  • Amy L Weaver
  • Vera J Suman

PURPOSE: Less than 20% of patients with melanoma who undergo sentinel lymph node (SLN) biopsy based on American Society of Clinical Oncology/Society of Surgical Oncology recommendations are SLN positive. We present a multi-institutional study to discover new molecular risk factors associated with SLN positivity in thin and intermediate-thickness melanoma.

PATIENTS AND METHODS: Gene clusters with functional roles in melanoma metastasis were discovered by next-generation sequencing and validated by quantitative polymerase chain reaction using a discovery set of 73 benign nevi, 76 primary cutaneous melanoma, and 11 in-transit melanoma metastases. We then used polymerase chain reaction to quantify gene expression in a model development cohort of 360 consecutive thin and intermediate-thickness melanomas and a validation cohort of 146 melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. Logic and logistic regression analyses were used to develop a model for the likelihood of SLN metastasis from molecular, clinical, and histologic variables.

RESULTS: ITGB3, LAMB1, PLAT, and TP53 expression were associated with SLN metastasis. The predictive ability of a model that included these molecular variables in combination with clinicopathologic variables (patient age, Breslow depth, and tumor ulceration) was significantly greater than a model that only considered clinicopathologic variables and also performed well in the validation cohort (area under the curve, 0.93; 95% CI, 0.87 to 0.97; false-positive and false-negative rates of 22% and 0%, respectively, using a 10% cutoff for predicted SLN metastasis risk).

CONCLUSION: The addition of cell adhesion-linked gene expression variables to clinicopathologic variables improves the identification of patients with SLN metastases within 90 days of melanoma diagnosis.

Original languageEnglish
JournalJournal of Clinical Oncology
Issue number23
Pages (from-to)2509-15
Number of pages7
Publication statusPublished - 10 Aug 2015
Externally publishedYes

    Research areas

  • Adult, Aged, Biomarkers, Tumor/analysis, Cell Adhesion, Female, Gene Expression Regulation, Neoplastic, Humans, Integrin beta3/analysis, Laminin/analysis, Logistic Models, Lymph Nodes/pathology, Lymphatic Metastasis, Male, Melanoma/chemistry, Middle Aged, Predictive Value of Tests, Risk Factors, Sentinel Lymph Node Biopsy, Skin Neoplasms/chemistry, Tissue Plasminogen Activator/analysis, Tumor Suppressor Protein p53/analysis

ID: 213886179