乳腺癌及癌前病变3号染色体短臂杂合性缺失的研究

目的研究乳腺癌及癌前病变中3号染色体短臂（3p）杂合性缺失（loss of heterozygosity,LOH）的发生情况。方法采用聚合酶链式反应及硝酸银染色等方法检测41例原发性乳腺癌及12例癌前病变中3p的11个微卫星位点LOH发生情况;用免疫组化方法检测40例乳腺癌中雌激素受体（ER）、孕激素受体（PR）、脆性组氨酸三联体（fragile histidine triad,FHIT）及人类MutL基因的同源基因（human MutL homologue,hMLH1）的表达情况。结果97％乳腺癌患者发生3p的LOH,检出率较高的位点是D3S1295（53．1％）、D3S1029（43．6％）和D3S1038（52．5％）,分别位于3p14、3021-p22和3p25。D3S1038位点LOH及hMLH1蛋白表达与部分临床病理学参数相关（P〈0．05）。D3S1295的LOH与FHIT蛋白表达负相关（P〈0．05）。癌前病变患者3pLOH发生率为41．7％,检出率较高的位点是D3S1295（27．3％）和D3S1029（16．7％）。最小共同丢失区位于3p14-p25。结论3p14-p25区段可能有与乳腺癌发生发展相关并影响乳腺癌生物学行为的候选抑癌基因,基因的部分缺失可影响其蛋白的表达。

Loss of heterozygosity on chromosome 3p in breast cancer and precancerous lesion

Objective To study the loss of heterozygosity(LOH)on chromosome 3p in breast cancers and precancerous lesion.Methods LOH at 11 microsatellite loci was detected in 41 cases of breast cancers and 12 cases of precancerous lesion by polymerase chain reaction and silver stain.The expressions of ER,PR,FHIT and hMLH1 were detected in breast cancer by immunohistochemistry.Results LOH on 3p was detected in 97% of breast cancers.D3S1295,D3S1029 and D3S1038 located at 3p14,3p21-p22 and 3p25 were identified as the loci with most frequent LOH(53.1%,43.6% and 52.5%).LOH of D3S1038 and expression of hMLH1 protein correlated with several clinicopathological features.LOH of D3S1295 had significant negative correlation with the expression of FHIT.In breast precancerous lesions,LOH on 3p was detected in 41.7% lesions.D3S1295 and D3S1029 were also identified as the most frequent LOH locus (27.3% and 16.7%).The smallest common LOH region seems likely lie between 3p14 and 3p25. Conclusions The smallest LOH region indicates the existence of breast tumor related genes and some of them affect gene expression.