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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 ofheterozygosity,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、3p21-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3p LOH 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。
Objective To investigate the occurrence of loss of heterozygosity (LOH) on chromosome 3 short arm (3p) in breast cancer and precancerous lesions. Methods Polymerase chain reaction (PCR) and silver nitrate staining were used to detect the occurrence of LOH in 11 microsatellite loci in 41 cases of primary breast cancer and 12 cases of precancerous lesions. Immunohistochemistry was used to detect 40 cases of breast cancer (PR), fragile histidine triad (FHIT) and human MutL homolog (human MutL homologue, hMLH1) were detected by Western blot. Results LOH detected by 3p in 97% of breast cancer patients was D3S1295 (53.1%), D3S1029 (43.6%) and D3S1038 (52.5%) at 3p14, 3p21-p22 and 3p25, respectively. The expression of LOH and hMLH1 at D3S1038 site was correlated with some clinicopathological parameters (P <0.05). The LOH of D3S1295 was negatively correlated with FHIT protein (P <0.05). The incidence of 3p LOH in patients with precancerous lesions was 41.7%, with D3S1295 (27.3%) and D3S1029 (16.7%) with high detection rates. The smallest common loss region is located at 3p14-p25. Conclusion The 3p14-p25 region may be a candidate tumor suppressor gene that is involved in the development of breast cancer and affects the biological behavior of breast cancer. Partial deletion of the gene may affect its expression.