Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma
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Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma. / Meves, Alexander; Nikolova, Ekaterina; Heim, Joel B; Squirewell, Edwin J; Cappel, Mark A; Pittelkow, Mark R; Otley, Clark C; Behrendt, Nille; Saunte, Ditte M; Lock-Andersen, Jorgen; Schenck, Louis A; Weaver, Amy L; Suman, Vera J.
In: Journal of Clinical Oncology, Vol. 33, No. 23, 10.08.2015, p. 2509-15.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma
AU - Meves, Alexander
AU - Nikolova, Ekaterina
AU - Heim, Joel B
AU - Squirewell, Edwin J
AU - Cappel, Mark A
AU - Pittelkow, Mark R
AU - Otley, Clark C
AU - Behrendt, Nille
AU - Saunte, Ditte M
AU - Lock-Andersen, Jorgen
AU - Schenck, Louis A
AU - Weaver, Amy L
AU - Suman, Vera J
N1 - © 2015 by American Society of Clinical Oncology.
PY - 2015/8/10
Y1 - 2015/8/10
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Biomarkers, Tumor/analysis
KW - Cell Adhesion
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Integrin beta3/analysis
KW - Laminin/analysis
KW - Logistic Models
KW - Lymph Nodes/pathology
KW - Lymphatic Metastasis
KW - Male
KW - Melanoma/chemistry
KW - Middle Aged
KW - Predictive Value of Tests
KW - Risk Factors
KW - Sentinel Lymph Node Biopsy
KW - Skin Neoplasms/chemistry
KW - Tissue Plasminogen Activator/analysis
KW - Tumor Suppressor Protein p53/analysis
U2 - 10.1200/JCO.2014.60.7002
DO - 10.1200/JCO.2014.60.7002
M3 - Journal article
C2 - 26150443
VL - 33
SP - 2509
EP - 2515
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 23
ER -
ID: 213886179