Tumor cell adhesion as a risk factor for sentinel lymph node metastasis in primary cutaneous melanoma

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

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
Sider (fra-til)2509-2515
Antal sider7
TidsskriftJournal of Clinical Oncology
Vol/bind33
Udgave nummer23
DOI
StatusUdgivet - 10 aug. 2015

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