title: Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study.
abstract: OBJECTIVE
  Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas.
  
  
  METHODS
  On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined.
  
  
  RESULTS
  Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (P(trend) < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage.
  
  
  CONCLUSIONS
  At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions.
authors.affiliation: Nancy E. Thomas, Pamela A. Groben, Honglin Hao, and David W. Ollila, University of North Carolina, Chapel Hill, NC; Klaus J. Busam, Irene Orlow, Anne S. Reiner, and Colin B. Begg, Memorial Sloan-Kettering Cancer Center, New York, NY; Lynn From, Women's College Hospital, Toronto, Ontario; Richard P. Gallagher, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada; Anne Kricker and Bruce K. Armstrong, The University of Sydney, Sydney, New South Wales; Alison Venn, Menzies Research Institute, Tasmania, Australia; Hoda Anton-Culver, University of California, Irvine; Stephen B. Gruber, University of Southern California, Los Angeles, CA; Roberto Zanetti and Stefano Rosso, Center for Cancer Prevention, Torino, Italy; Terence Dwyer, International Agency for Research on Cancer, Lyon, France; Peter A. Kanetsky, University of Pennsylvania, Philadelphia, PA; Li Luo, Susan Paine, and Marianne Berwick, University of New Mexico, Albuquerque, NM; and Homer Wilcox, New Jersey Department of Health, Trenton, NJ.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Thomas
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Busam
authors.forename: Lynn
authors.initials: L
authors.lastname: From
authors.forename: Anne
authors.initials: A
authors.lastname: Kricker
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Armstrong
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
authors.forename: Richard P
authors.initials: RP
authors.lastname: Gallagher
authors.forename: Roberto
authors.initials: R
authors.lastname: Zanetti
authors.forename: Stefano
authors.initials: S
authors.lastname: Rosso
authors.forename: Terence
authors.initials: T
authors.lastname: Dwyer
authors.forename: Alison
authors.initials: A
authors.lastname: Venn
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kanetsky
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Groben
authors.forename: Honglin
authors.initials: H
authors.lastname: Hao
authors.forename: Irene
authors.initials: I
authors.lastname: Orlow
authors.forename: Anne S
authors.initials: AS
authors.lastname: Reiner
authors.forename: Li
authors.initials: L
authors.lastname: Luo
authors.forename: Susan
authors.initials: S
authors.lastname: Paine
authors.forename: David W
authors.initials: DW
authors.lastname: Ollila
authors.forename: Homer
authors.initials: H
authors.lastname: Wilcox
authors.forename: Colin B
authors.initials: CB
authors.lastname: Begg
authors.forename: Marianne
authors.initials: M
authors.lastname: Berwick
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D006801:Humans; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011159:Population Surveillance / Q000379:methods*; D011379:Prognosis; D012878:Skin Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate; D013997:Time Factors