title: Tumor Cell Adhesion As a Risk Factor for Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. meves.alexander@mayo.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Meves
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Nikolova
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Heim
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Squirewell
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Cappel
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Pittelkow
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Clark C
authors.initials: CC
authors.lastname: Otley
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nille
authors.initials: N
authors.lastname: Behrendt
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ditte M
authors.initials: DM
authors.lastname: Saunte
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jorgen
authors.initials: J
authors.lastname: Lock-Andersen
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Louis A
authors.initials: LA
authors.lastname: Schenck
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Weaver
authors.affiliation: Alexander Meves, Ekaterina Nikolova, Joel B. Heim, Edwin J. Squirewell, Clark C. Otley, Louis A. Schenck, Amy L. Weaver, and Vera J. Suman, Mayo Clinic, Rochester, MN; Mark A. Cappel, Mayo Clinic, Jacksonville, FL; Mark R. Pittelkow, Mayo Clinic, Scottsdale, AZ; and Nille Behrendt, Ditte M. Saunte, and Jorgen Lock-Andersen, Hospital Roskilde, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002448:Cell Adhesion; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039661:Integrin beta3 / Q000032:analysis; D007797:Laminin / Q000032:analysis; D016015:Logistic Models; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000737:chemistry / Q000473:pathology*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012307:Risk Factors; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000737:chemistry / Q000473:pathology*; D010959:Tissue Plasminogen Activator / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; C061248:ITGB3 protein, human; D039661:Integrin beta3; C478221:LAMB1 protein, human; D007797:Laminin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C067262:PLAT protein, human; D010959:Tissue Plasminogen Activator