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

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, 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

33 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Journal of Clinical Oncology
Vol/bind	33
Udgave nummer	23
Sider (fra-til)	2509-15
Antal sider	7
ISSN	0732-183X
DOI	https://doi.org/10.1200/JCO.2014.60.7002
Status	Udgivet - 10 aug. 2015
Udgivet eksternt	Ja

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10.1200/JCO.2014.60.7002

Citationsformater

Meves, A., Nikolova, E., Heim, J. B., Squirewell, E. J., Cappel, M. A., Pittelkow, M. R., Otley, C. C., Behrendt, N., Saunte, D. M., Lock-Andersen, J., Schenck, L. A., Weaver, A. L., & Suman, V. J. (2015). Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma. Journal of Clinical Oncology, 33(23), 2509-15. https://doi.org/10.1200/JCO.2014.60.7002

Meves, A, Nikolova, E, Heim, JB, Squirewell, EJ, Cappel, MA, Pittelkow, MR, Otley, CC, Behrendt, N, Saunte, DM, Lock-Andersen, J, Schenck, LA, Weaver, AL & Suman, VJ 2015, 'Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma', Journal of Clinical Oncology, bind 33, nr. 23, s. 2509-15. https://doi.org/10.1200/JCO.2014.60.7002

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

abstract = "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.",

keywords = "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",

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

note = "{\textcopyright} 2015 by American Society of Clinical Oncology.",

year = "2015",

month = aug,

day = "10",

doi = "10.1200/JCO.2014.60.7002",

language = "English",

volume = "33",

pages = "2509--15",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "23",

}

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

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

SN - 0732-183X

VL - 33

SP - 2509

EP - 2515

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 23

ER -

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

Abstract

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