title: A high proliferative index of recurrent melanoma is associated with worse survival.
abstract: OBJECTIVE
  Previous melanoma studies evaluating prognostic factors of survival at recurrence have focused on primary tumor characteristics and clinical variables at first recurrence. We examined the prognostic relevance of recurrent tumor proliferation.
  
  
  METHODS
  114 melanoma patients with available recurrent tissues who were prospectively enrolled at New York University Medical Center were studied. Standard of care prognostic variables (e.g. stage at initial diagnosis and lactate dehydrogenase level) and recurrent tissue expression of proliferative marker Ki-67 were evaluated for their association with overall survival.
  
  
  RESULTS
  High Ki-67 expression was observed in 57 (50%) of the 114 recurrent melanomas. On univariate analysis, the median overall survival of patients whose recurrent tumors overexpressed Ki-67 was significantly shorter than that of patients whose recurrent tumors had low Ki-67 expression (3.6 vs. 9.5 years, p = 0.03). On multivariate analysis, a high proliferative index of the recurrent melanoma remained an independent predictor of worse overall survival, controlling for stage at initial diagnosis, disease-free survival, and stage at first recurrence [HR = 2.09 (95% CI 1.24-3.54), p = 0.006].
  
  
  CONCLUSIONS
  Our results demonstrate the prognostic relevance of tumor proliferation in recurrent melanoma patients. Data also support restratification of risk assessment upon recurrence that considers tumor biology in addition to clinical variables evaluated as part of the standard of care.
authors.affiliation: The New York University Interdisciplinary Melanoma Cooperative Group, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Ting J
authors.initials: TJ
authors.lastname: Tu
authors.forename: Michelle W
authors.initials: MW
authors.lastname: Ma
authors.forename: Stefano
authors.initials: S
authors.lastname: Monni
authors.forename: Amy E
authors.initials: AE
authors.lastname: Rose
authors.forename: Herman
authors.initials: H
authors.lastname: Yee
authors.forename: Farbod
authors.initials: F
authors.lastname: Darvishian
authors.forename: David
authors.initials: D
authors.lastname: Polsky
authors.forename: Russell S
authors.initials: RS
authors.lastname: Berman
authors.forename: Richard L
authors.initials: RL
authors.lastname: Shapiro
authors.forename: Anna C
authors.initials: AC
authors.lastname: Pavlick
authors.forename: Madhu
authors.initials: M
authors.lastname: Mazumdar
authors.forename: Iman
authors.initials: I
authors.lastname: Osman
mesh_terms: D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012878:Skin Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*
chemical_list: D019394:Ki-67 Antigen; D007770:L-Lactate Dehydrogenase