Study of loss of heterozygosity at 9p21 and P16 expression in gastrointestinal stromal tumors

Objective To evaluate the impact of loss of heterozygosity (LOH) at chromosome 9p21 and P16INK4A(CDKN2A) expression on the prognosis of gastrointestinal stromal tumor (GIST). Methods A total of 51 cases with GISTs were characterized by immunohistochemistry and evaluated for LOH at 9p21 by microsatellite analysis in 4 markers(D9S1751, D9S1846, D9S942 and D9S1748). Associations of LOH at 9p21 and P16INK4A expression encoded by CDKN2A with clinicopathological parameters and prognosis in GISTs were analyzed. Results The frequency of 9p21 LOH was 37.0% (10/27) at D9S1751, 37.5%(12/32) at D9S1846, 42.1%(16/38) at D9S942 and 24.2%(8/33) at D9S1748. The overall frequency of LOH at 9p21 was 63.3%(31/49). In 21 samples of 51 GISTs(41.2%), P16 expression was not detected. Loss of P16 expression was 60%(12/20) in high risk group and 23.5%(4/17) in very low and low risk groups(P＜0.05). The 5-year overall survival rate of p16-negative patients was 70.8%, while in P16-positive patients it was 92.0%(P＜0.05). Conclusions LOH at 9p21 is a frequent event in GIST. Loss of CDKN2A gene at 9p21 may contribute to the progression and malignant transformation of GIST. P16 expression in GIST is associated with prognosis. Key words: Gastrointestinal stromal tumors;  Loss of heterozygosity;  Gene,P16;  Prognosis