原发性胃癌中DCC抑癌基因杂合性丢失的研究

Study on loss of heterozygosity of DCC in primary gastric carcinoma.

目的:探讨原发性胃癌组织中结直肠癌缺失基因(deletedincolorectalcarcinoma,DCC)杂合性丢失(lossofhet鄄erozygosity,LOH)的情况及其与胃癌临床病理学间的关系。方法:用多聚酶链反应鄄单链构相多态性(PCR鄄SSCP)银染法分析49例原发性胃癌组织中DCC的杂合性丢失。结果:D18S484位点发生LOH的频率为26.6%(12/45),D18S487为23.9%(11/46),DCC发生LOH的频率为36.7%(18/49)。36.8%(7/19)的肠型胃癌发生DCCLOH,24.0%(6/25)的弥漫型胃癌发生DCCLOH,而100%(5/5)的混合型胃癌为DCCLOH(P<0.05)。在淋巴结有转移的胃癌中,52%(13/25)的原发性胃癌发生DCCLOH,无转移者中为20.8%(5/24)(P<0.05);发生远处转移者,原发性胃癌DCCLOH为100%(3/3),而无转移者为32.6%(15/46)(P<0.05);在TNMⅢ、Ⅳ期中DCCLOH为50.0%(12/24),有高于TNMⅠ、Ⅱ期(24%,6/25)的趋势(P=0.059)。DCCLOH与病人的性别、年龄、肿瘤发生部位、大小、组织学分级均无统计学意义(P>0.05)。结论:DCC的杂合性丢失可能在胃癌的发展和转移中起重要作用,是胃癌发展后期的重要分子事件。

Objective:To elucidate the role of loss of heterozygosity(LOH)of DCC in carcinogenesis and development of gastric carcinoma and its relationship wifh clinicopathological factors in primary gastric carcinoma.Methods:Forty-nine cases of primary gastric carcinoma were studiel by polymerase chain reactionsingle strand conformation polymorphism(PCR-SSCP)and silver staining to detect the loss of heterozygosity(LOH)of DCC.Results:The incidence of LOH in D18S484was ob-served in26.6%(12/45);in D18S487,23.9%(11/46);in DCC,36.7%(18/49).The rate of DCC LOH was36.8%(7/19)in fhe intestinal-type.of gastric camcer,24.0%(6/25)in fhe diffuse-type and and100%(5/5)in fhe mixed-type(P<0.05).The prevalence of DCC LOH was significantly higher in cases wifhpatients with lymph node metastasis(52%)than fhose in those without lymph node metastasis(20.8%)(P<0.05),and X more significantly higher in cases wifh distant metatasis(P<0.05).There was a trend towards a higher in incidence of DCC LOH in StogesⅢδⅣcases those in SragosⅠandⅡ(24%)(P=0.059).Conclusions:The DCC LOH miyht enhance fhe progression andoccurrence of metastasis in gastric carcinoma.