Journal Article
. 2015 Jul;33(23).
doi: 10.1200/JCO.2014.60.7002.

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

Alexander Meves 1 Ekaterina Nikolova 2 Joel B Heim 2 Edwin J Squirewell 2 Mark A Cappel 2 Mark R Pittelkow 2 Clark C Otley 2 Nille Behrendt 2 Ditte M Saunte 2 Jorgen Lock-Andersen 2 Louis A Schenck 2 Amy L Weaver 2 Vera J Suman 2 
  • PMID: 26150443
  •     54 References
  •     19 citations


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.

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