Mutant ER and Loss of Response for Hormone Therapy in Breast Cancer

我们做了两种研究。ER基因变异我们于1994年对44例乳腺癌患者进行了雌激素受体(ER)基因外显子2和7的基因变异研究。[材料与方法]从99例乳腺癌切除后即刻冰冻组织中提取942例DNA，用聚合酶链式反应-单链构象多态性分析方法检测外显子2、3、4、5、7的变异情况。ER基因变异与肿瘤分期、ER、PGR、PS2蛋白、P53蛋白及病理类型无关。但异倍体与异倍体之间存在显著相关性，因此15例中只有1例c-erb B-2阳性。变异阴性组的总体生存率好于变异阳性组，但差异无统计学意义。在外显子3和7都有VALIANT基因的组中，总体存活率显著低于没有外显子3和7基因变异组。[材料与方法]采用免疫组织化学方法检测305例乳腺癌组织中PS2蛋白的表达，并与其他临床病理因素进行比较。[结果]PS2蛋白的表达与肿瘤大小、淋巴结状态、转移、分期、组织学分型、倍体、P53、cerbB-2无关。PS2蛋白表达与ER、PgR呈显著正相关，后者(P&lt；0.0001)显著高于前者(P=0.0004)。PS2阳性组总生存率明显高于pS2阴性组(P=0.0035)。这项研究表明，PS2蛋白将作为一个有利的预后因素生存，其阳性有可能表明候选的激素治疗。

We have done 2 kind of study.1. ER gene variantWe in vestigated the gene variants at exon 2 and 7 of Estrogene Receptor (ER) gene in 44 breast cancer cases in 1994. Furthermore, in 1995, we increased range and case number and in vestigated gene variant.[Materials and Methods] We extr942ed DNA from 99 breast cancer tissues which were frozen immediately after resection, and evaluated the variant at exon 2,3,4,5,7 by PCR-SSCP method.[Results] Sixteen variants were detected in 99 cases. There was no correlation between ER gene variant and Tum-stage, ER,PgR,pS2 protein, p53 or pathological classification. But there was significant correlation between variant and aneuploid, and therfore only one c-erbB-2 positive case was variant in evaluated 15 cases. Overall survival was better in the variant negative group than in the variant positive group, but it was not significant. Overall survival was significantly low in the group with valiant at both exon 3 and 7 than in the group with out variant.2. pS2 expression[Materials and Methods] We evaluated the pS2 protein expression in 305 women with primary breast cancer by immunohistochemical method and compare it with their other clinicopathological factors.[Results] There was no significant correlation between the pS2 expression and tumor size, lymphnode status, metastasis, stage, histological classification, ploidy, p53 or cerbB-2. The pS2 protein expression has significant positive correlation with ER and PgR,the latter (P<0.0001) has stronger significance than the former (P=0.0004). Overall survival was significantly (P=0.0035) better in the pS2 positive group than that in the negative group. This study suggests that the pS2 protein will act as a favorable prognostic factor survival and its positivity has potential to indicate the candidate for hormone therapy.