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

我们做了两种研究。1.我们对1994年44例乳腺癌患者雌激素受体（ER）基因第2、7外显子的基因变异进行了研究。此外，在1995年，我们增加了范围和病例数，并调查了基因变异。[材料与方法]从99例乳腺癌术后即刻冰冻组织中提取942份DNA，采用PCR-SSCP方法检测外显子2、3、4、5、7的变异。[结果] 99例患者共检出16种变异。ER基因变异与肿瘤分期、ER、PgR、pS2蛋白、p53及病理分型均无相关性。但变异与非整倍体之间有显著相关性，因此15例c-erbB-2阳性者中仅有1例为变异。变异阴性组的总生存率高于变异阳性组，但无显著性差异。在外显子3和7上均携带valiant基因的患者的总生存率显著低于未携带valiant基因的患者.【材料与方法】应用免疫组化方法检测305例原发性乳腺癌组织中pS2蛋白的表达，并与其他临床病理因素进行比较。[结果] pS2表达与肿瘤大小、淋巴结转移、分期、组织学分型、倍体、p53和cerbB-2均无明显相关性。pS2蛋白表达与ER、PgR呈显著正相关，后者（P<0.0001）显著高于前者（P=0.0004）。pS2阳性组的总生存率显著高于阴性组（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和其阳性有可能表明候选激素治疗。

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.