title: Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database.
abstract: OBJECTIVE
  The aim of this study was to assess the independent prognostic value of primary tumor mitotic rate compared with other clinical and pathologic features of stages I and II melanoma.
  
  
  METHODS
  From the American Joint Committee on Cancer (AJCC) melanoma staging database, information was extracted for 13,296 patients with stages I and II disease who had mitotic rate data available.
  
  
  RESULTS
  Survival times declined as mitotic rate increased. Ten-year survival ranged from 93% for patients whose tumors had 0 mitosis/mm(2) to 48% for those with ≥ 20/mm(2) (P < .001). Mean number of mitoses/mm(2) increased as the primary melanomas became thicker (1.0 for melanomas ≤ 1 mm, 3.5 for 1.01 to 2.0 mm, 7.3 for 3.01 to 4.0 mm, and 9.6 for > 8 mm). Ulceration was also associated with a higher mitotic rate; 59% of ulcerated melanomas had ≥ 5 mitoses/mm(2) compared with 16% of nonulcerated melanomas (P < .001). In a multivariate analysis of 10,233 patients, the independent predictive factors for survival in order of statistical significance were as follows: tumor thickness (χ(2) = 104.9; P < .001), mitotic rate (χ(2) = 67.0; P < .001), patient age (χ(2) = 48.2; P < .001), ulceration (χ(2) = 46.4; P < .001), anatomic site (χ(2) = 34.6; P < .001), and patient sex (χ(2) = 33.9; P < .001). Clark level of invasion was not an independent predictor of survival (χ(2) = 3.2; P = .37).
  
  
  CONCLUSIONS
  A high mitotic rate in a primary melanoma is associated with a lower survival probability. Among the independent predictors of melanoma-specific survival, mitotic rate was the strongest prognostic factor after tumor thickness.
authors.affiliation: Melanoma Institute Australia, The Poche Centre, Sydney, New South Wales, Australia. john.thompson@melanoma.org.au
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
authors.forename: Seng-Jaw
authors.initials: SJ
authors.lastname: Soong
authors.forename: Charles M
authors.initials: CM
authors.lastname: Balch
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.forename: Shouluan
authors.initials: S
authors.lastname: Ding
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Coit
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Gimotty
authors.forename: Timothy
authors.initials: T
authors.lastname: Johnson
authors.forename: Marcella M
authors.initials: MM
authors.lastname: Johnson
authors.forename: Stanley P
authors.initials: SP
authors.lastname: Leong
authors.forename: Merrick I
authors.initials: MI
authors.lastname: Ross
authors.forename: David R
authors.initials: DR
authors.lastname: Byrd
authors.forename: Natale
authors.initials: N
authors.lastname: Cascinelli
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Cochran
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McMasters
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.forename: Donald L
authors.initials: DL
authors.lastname: Morton
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
mesh_terms: D016208:Databases, Factual; D006801:Humans; D053208:Kaplan-Meier Estimate; D008545:Melanoma / Q000401:mortality* / Q000473:pathology; D008938:Mitosis / Q000502:physiology; D008940:Mitotic Index; D009367:Neoplasm Staging / Q000379:methods*; D011379:Prognosis; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000401:mortality* / Q000473:pathology