目的探讨荧光原位杂交法(Fluorescence in situ hybridization,FISH)检测乳腺癌HER-2基因扩增在临床病理诊断及分子靶向治疗中应用的可能性。方法用FISH技术和免疫组化(Immunohisto-chemistry,IHC)技术检测50例乳腺导管癌石蜡包埋标本...目的探讨荧光原位杂交法(Fluorescence in situ hybridization,FISH)检测乳腺癌HER-2基因扩增在临床病理诊断及分子靶向治疗中应用的可能性。方法用FISH技术和免疫组化(Immunohisto-chemistry,IHC)技术检测50例乳腺导管癌石蜡包埋标本并比较两种方法的结果以及与临床病理的关系。结果16/50例HER-2蛋白表达阳性,其中强阳性5例,中度阳性9例,弱阳性2例;11/50(22%)例乳腺癌标本FISH技术检测HER-2基因扩增阳性,其中5/5为免疫组化HER-2蛋白强阳性病例;6/9为中度阳性病例,其中1例为17号染色体多倍体与HER-2基因扩增。HER-2基因扩增与蛋白表达与乳腺癌转移有关(P<0.05)。结论FISH技术可稳定地检测用IHC确定的HER-2蛋白阳性乳腺癌中HER-2基因的扩增状况,并用于临床赫赛汀分子靶向治疗病例的筛选。展开更多
Overexpression and activation of HER-2/neu (also known as c-erbB-2), a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-ther...Overexpression and activation of HER-2/neu (also known as c-erbB-2), a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-therapy. Wild-type p53 is crucial in regulating cell growth and apoptosis and is found to be mutated or deleted in 60-70% of human cancers. And some cancers with a wild-type p53 do not have normal p53 function, suggesting that it is implicated in a complex process regulated by many factors. In the present study, we showed that the overexpression of HER-2/neu could decrease the amount of wild-type p53 protein via activating PI3K pathway, as well as inducing MDM2 nuclear translocation in MCF7 human breast cancer cells. Blockage of PI3K pathway with its specific inhibitor LY294002 caused Gl-S phase arrest, decreased cell growth rate and increased chemo- and radio-therapeutic sensitivity in MCF7 cells expressing wild-type p53. However, it did not increase the sensitivity to adriamycin in MDA-MB-453 breast cancer cells containing mutant p53. Our study indicates that blocking PI3K pathway activation mediated by HER-2/neu overexpression may be useful in the treatment of breast tumors with HER-2/neu overexpression and wild-type p53.展开更多
文摘目的探讨荧光原位杂交法(Fluorescence in situ hybridization,FISH)检测乳腺癌HER-2基因扩增在临床病理诊断及分子靶向治疗中应用的可能性。方法用FISH技术和免疫组化(Immunohisto-chemistry,IHC)技术检测50例乳腺导管癌石蜡包埋标本并比较两种方法的结果以及与临床病理的关系。结果16/50例HER-2蛋白表达阳性,其中强阳性5例,中度阳性9例,弱阳性2例;11/50(22%)例乳腺癌标本FISH技术检测HER-2基因扩增阳性,其中5/5为免疫组化HER-2蛋白强阳性病例;6/9为中度阳性病例,其中1例为17号染色体多倍体与HER-2基因扩增。HER-2基因扩增与蛋白表达与乳腺癌转移有关(P<0.05)。结论FISH技术可稳定地检测用IHC确定的HER-2蛋白阳性乳腺癌中HER-2基因的扩增状况,并用于临床赫赛汀分子靶向治疗病例的筛选。
文摘Overexpression and activation of HER-2/neu (also known as c-erbB-2), a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-therapy. Wild-type p53 is crucial in regulating cell growth and apoptosis and is found to be mutated or deleted in 60-70% of human cancers. And some cancers with a wild-type p53 do not have normal p53 function, suggesting that it is implicated in a complex process regulated by many factors. In the present study, we showed that the overexpression of HER-2/neu could decrease the amount of wild-type p53 protein via activating PI3K pathway, as well as inducing MDM2 nuclear translocation in MCF7 human breast cancer cells. Blockage of PI3K pathway with its specific inhibitor LY294002 caused Gl-S phase arrest, decreased cell growth rate and increased chemo- and radio-therapeutic sensitivity in MCF7 cells expressing wild-type p53. However, it did not increase the sensitivity to adriamycin in MDA-MB-453 breast cancer cells containing mutant p53. Our study indicates that blocking PI3K pathway activation mediated by HER-2/neu overexpression may be useful in the treatment of breast tumors with HER-2/neu overexpression and wild-type p53.
