title: Loss of chromosome 9p21 and decreased p16 expression correlate with malignant gastrointestinal stromal tumor.
abstract: OBJECTIVE
  To investigate loss of heterozygosity (LOH) of chromosome 9p21 and the prognostic relevance of p16 expression in gastrointestinal stromal tumor (GIST).
  
  
  METHODS
  Fifty-one GIST patients (30 men and 21 women; median age 59 years; range 29-80 years) treated surgically within a 10-year period were grouped by aggressive behavior risk (17 with very low and low, 14 intermediate, and 20 high risk). GISTs were characterized immunohistochemically and evaluated for LOH of 9p21 by microsatellite analysis at D9S1751, D9S1846, D9S942, and D9S1748. LOH of 9p21 and immunohistochemical expression of p16 protein encoded at 9p21 were correlated with clinicopathological parameters, and the prognostic significance of p16 alterations was evaluated.
  
  
  RESULTS
  Thirty-one (63.3%) cases showed LOH with at least one microsatellite marker. LOH frequency was 37.0% at D9S1751, 37.5% at D9S1846, 42.1% at D9S942, and 24.2% at D9S1748. There was a higher LOH frequency of D9S942 in high-risk than in non-high-risk tumors (P < 0.05, χ(2) = 4.47). Gender, age, tumor size and site were not correlated with allelic loss. Ninety percent (18/20) of the GIST patients in the high risk group showed LOH with at least one of the 9p21 markers, while 57.1% (8/14) in the intermediate risk group and 33.3% (5/15) in the very low and low risk groups, respectively (P < 0.05, χ(2) = 12.16). Eight (28.5%) of 31 patients with LOH and 1 (5.6%) of 18 patients without LOH died of the disease during the follow-up period. Loss of p16 protein expression occurred in 41.2%, but in 60% of the high risk group and 23.5% of the very low and low risk groups (P < 0.05, χ(2) = 4.98). p16 loss was associated with poor prognosis (P < 0.05, χ(2) = 4.18): the 3- and 5-year overall survival rates were 84.8% and 70.8% for p16-negative and 100% and 92.0% for p16-positive patients, respectively.
  
  
  CONCLUSIONS
  LOH at 9p21 appears to play an important role in GIST progression; decreased p16 expression in GIST is highly predictive of poor outcome.
authors.affiliation: Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Zhao
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Shen
authors.forename: Dan-Ping
authors.initials: DP
authors.lastname: Shen
authors.forename: Xing-Zhi
authors.initials: XZ
authors.lastname: Ni
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Wu
authors.forename: Yan-Ying
authors.initials: YY
authors.lastname: Shen
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16