3p杂合性缺失与乳腺癌发生发展相关性的研究

目的：探讨染色体3p区域多个等位基因位点的杂合性缺失（loss of heterozygos ity,LOH）与乳腺癌发生发展之间的相关性。方法：采用微切割技术和PCR-SSLP银染技术结合微卫星重复序列多态性,分析45例乳腺癌石蜡库存标本中3p25、3p22-24、3p21.3、3p21.2-21.3、3p14.3、3p14.2和3p12等多个位点的杂合性缺失（LOH）。结果：45例乳腺癌标本中的LOH检出率分别为3p25（48%）、3p22-24（61%）、3p21.3（69%）、3p21.2-21.3（58%）、3p14.3（41%）、3p14.2（45%）和3p12（35%）,其中3p21.3区域LOH出现率最高（69%）。分析各3p位点LOH与临床分期、淋巴结转移和雌孕激素受体（ER、PR）的相关关系,发现3p25区的LOH与孕激素受体表达的缺失之间具有相关性（P=0.006）;3p22-24区的LOH与乳腺癌临床分期之间具有相关性（P=0.009）。结论：通过联合检测染色体3p区域多个位点的LOH将有助于乳腺癌的诊断和判断患者的预后。

Study of Relationship of 3p Allele Loss and Pathogenesis of Breast Cancer

Objective:To investigate the frequency of loss of heterozygosity(LOH) at several 3p regions in breast cancer tissues.Methods:Forty-five archival,paraffin-embedded,surgically resected breast cancer specimens were studied.Precisely identified malignant and normal lymph node tissues were microdissected from stained slides and analyzed for allele loss using polymerase chain reaction-based assays for dinucleotide repeat polymorphisms at six chromosome 3p loci(3p25,3p22-24,3p21.3,3p21.2-21.3,3p14.3,3p14.2,and 3p12).Results:The 3p21.3 region had the highest frequency of LOH(67%),followed by 3p22-24(61%),3p21.2-21.3(58%),3p25(48%),3p14.2(45%),3p14.3(41%),and 3p12(35%).There was a statistically significant correlation between loss of progesterone receptor expression and LOH at 3p25(P=0.006) and poor clinical stage and LOH at 3p22-24 (P=0.009).Conclusions:These findings suggest that the measurement of LOH at 3p may be an useful predicting marker for diagnosis and prognosis of patients with breast cancer.