title: Ki-67: a prognostic factor for low-grade glioma?
abstract: OBJECTIVE
  Immunohistochemical techniques were used to detect the expression of Ki-67, a nuclear proliferation marker, in 180 low-grade glioma tumor specimens to determine whether Ki-67 is a prognostic predictor of survival or tumor recurrence.
  
  
  METHODS
  A clinical database of 180 low-grade glioma patients (35 children aged </=18 years and 145 adults) was compiled. Eighty patients had received postoperative radiotherapy (RT) and 100 patients had had RT deferred until the time of tumor progression/recurrence. Ki-67 indexes were evaluated retrospectively on tumor specimens from these patients using a semiautomated computer analysis technique. Ten observations were averaged per patient. The maximal Ki-67 value was recorded.
  
  
  RESULTS
  The correlation between the Ki-67 index and survival was much higher for the averaged Ki-67 value than for the maximal value. Of the tumor specimens, 29% had a negative Ki-67 index (i.e., zero Ki-67 positive cells) and 7.7% had an average Ki-67 index of >/=5%. An average Ki-67 value of >/=5% was prognostically significant for reduced cause-specific survival (CSS, p = 0.05) and a Ki-67 level >/=10% was strongly significant of a poor survival outcome (p = 0.009). Ki-67 was not prognostically significant for progression-free survival. Other prognostically significant factors for CSS included age (p = 0.05), Karnofsky performance status (p = 0.0001), radiation dose (p = 0.02), extent of surgical resection (biopsy vs. others, p = 0.004), and timing of radiation (p = 0.0005). Ki-67 did not remain an independent statistically significant factor for CSS on multivariate analysis. Age and Ki-67 positivity (both maximal and average values) directly correlated (i.e., advancing age was associated with a higher Ki-67 index). When the patient group was further subdivided by age and timing of RT (postoperative vs. deferred), the prognostic significance of Ki-67 for CSS was lost. Within the deferred RT subgroup, a maximal Ki-67 >2% was associated with a worsened CSS. Within the pediatric population, Ki-67-negative patients had a 5-year CSS and progression-free survival of 100%. The 5-year CSS and progression-free survival declined significantly to 84% and 67% for patients with tumors demonstrating any degree of Ki-67 positivity (p = 0.005 and p = 0.006, respectively).
  
  
  CONCLUSIONS
  Ki-67 is a useful predictor of CSS in low-grade gliomas; however, it is not independent of other prognostic factors, particularly age. Although Ki-67 was not helpful in predicting which adult patients were likely to benefit from postoperative RT, the results of the present study indicate a possible utility in the selection of pediatric patients for RT and in the selection of poorer prognosis patients for clinical trials.
authors.affiliation: Department of Radiation Oncology, London Regional Cancer Centre and University of Western Ontario, London, Ontario, Canada. barb.fisher@lrc.on.ca
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Fisher
authors.forename: Elitza
authors.initials: E
authors.lastname: Naumova
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Leighton
authors.forename: George N
authors.initials: GN
authors.lastname: Naumov
authors.forename: Nancy
authors.initials: N
authors.lastname: Kerklviet
authors.forename: David
authors.initials: D
authors.lastname: Fortin
authors.forename: David R
authors.initials: DR
authors.lastname: Macdonald
authors.forename: J Gregory
authors.initials: JG
authors.lastname: Cairncross
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Bauman
authors.forename: Larry
authors.initials: L
authors.lastname: Stitt
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001932:Brain Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D002648:Child; D005260:Female; D005910:Glioma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D011379:Prognosis
chemical_list: D019394:Ki-67 Antigen