Brief Article
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World J Gastroenterol. Oct 7, 2010; 16(37): 4716-4724
Published online Oct 7, 2010. doi: 10.3748/wjg.v16.i37.4716
Loss of chromosome 9p21 and decreased p16 expression correlate with malignant gastrointestinal stromal tumor
Yun Zhang, Hui Cao, Ming Wang, Wen-Yi Zhao, Zhi-Yong Shen, Dan-Ping Shen, Xing-Zhi Ni, Zhi-Yong Wu, Yan-Ying Shen, Yan-Yan Song
Yun Zhang, Hui Cao, Ming Wang, Wen-Yi Zhao, Zhi-Yong Shen, Dan-Ping Shen, Xing-Zhi Ni, Zhi-Yong Wu, Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Yan-Ying Shen, Department of Pathology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
Yan-Yan Song, Section of Statistics Teaching and Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Author contributions: Zhang Y, Cao H and Wu ZY conceived and designed this study; Zhang Y conducted the experiment and wrote the paper; Shen YY conducted experiment; Song YY dealt with statistical analysis; Wang M, Zhao WY and Shen ZY collected the data; Shen DP and Ni XZ analyzed and interpreted the data; all authors approved the final version of the article.
Supported by Key Discipline Project of Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. RJ4101304
Correspondence to: Hui Cao, MD, PhD, Department of General Surgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. caohuishcn@hotmail.com
Telephone: +86-21-68383751 Fax: +86-21-58394262
Received: April 26, 2010
Revised: June 22, 2010
Accepted: June 29, 2010
Published online: October 7, 2010
Abstract

AIM: 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, χ2 = 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, χ2 = 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, χ2 = 4.98). p16 loss was associated with poor prognosis (P < 0.05, χ2 = 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.

CONCLUSION: LOH at 9p21 appears to play an important role in GIST progression; decreased p16 expression in GIST is highly predictive of poor outcome.

Keywords: Gastrointestinal stromal tumor; Loss of heterozygosity; p16; Prognosis; Tumor suppressor gene