Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma
Research output: Contribution to journal › Journal article › Research › peer-review
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 language | English |
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Journal | Journal of Clinical Oncology |
Volume | 33 |
Issue number | 23 |
Pages (from-to) | 2509-15 |
Number of pages | 7 |
ISSN | 0732-183X |
DOIs | |
Publication status | Published - 10 Aug 2015 |
Externally published | Yes |
- 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
Research areas
ID: 213886179