CAJ | 학술논문

背景与目的：乳腺癌患者对化疗药物耐药是导致化疗失败的主要原因。有研究证实，肿瘤干细胞标志物乙醛脱氢酶1(aldehyde dehydrogenase 1，ALDH1)与某些抗癌药物(如环磷酰胺、顺铂等)的耐药有关，并发现经这些药物治疗后的患者癌灶细胞中ALDH1的含量较治疗前高。乳腺癌耐药蛋白(breast cancer resistance protein，BCRP)不仅在正常组织中表达，更高表达于治疗后的乳腺癌中，提示这可能与肿瘤耐药机制相关。关于在乳腺癌患者中两者是否存在共表达的研究很少，本研究主要探讨ALDH1、BCRP与临床病理特征的关系及两种蛋白表达之间的相关性。方法：采用免疫组化法检测乳腺浸润性导管癌组织石蜡切片中ALDH1与BCRP的表达，研究并探讨它们与临床病理特征的关系以及两者表达之间是否有相关性。结果：ALDH1、BCRP在乳腺癌及癌旁乳腺组织中表达差异有统计学意义(χ2=14.685，P=0.000；χ2=12.243，P=0.000)。ALDH1的表达与患者年龄、病理分期、腋窝淋巴结转移、组织学分级及雌激素受体(estrogen receptor，ER)、孕激素受体(progesterone receptor，PR)、人类表皮生长因子受体(human epidermal growth factor receptor，HER-2)状态均无关(P>0.05)；BCRP的表达与HER-2高表达有关，HER-2高表达组的癌组织中BCRP阳性表达率较高，差异有统计学意义(χ2＝5.289，P＝0.021)。BCRP的表达与患者年龄、肿瘤分化程度、腋窝淋巴结转移、病理分期及ER、PR状态无关(P>0.05)；乳腺癌肿瘤干细胞标志物ALDH1与BCRP无相关性(r=-0.039，P=0.786)。结论：ALDH1可能是区别于其他耐药蛋白的一种独立的生物学因子，参与乳腺癌的化疗耐药或肿瘤的侵袭、转移等恶性生物学行为。
배경여목적：유선암환자대화료약물내약시도치화료실패적주요원인。유연구증실，종류간세포표지물을철탈경매1(aldehyde dehydrogenase 1，ALDH1)여모사항암약물(여배린선알、순박등)적내약유관，병발현경저사약물치료후적환자암조세포중ALDH1적함량교치료전고。유선암내약단백(breast cancer resistance protein，BCRP)불부재정상조직중표체，경고표체우치료후적유선암중，제시저가능여종류내약궤제상관。관우재유선암환자중량자시부존재공표체적연구흔소，본연구주요탐토ALDH1、BCRP여림상병리특정적관계급량충단백표체지간적상관성。방법：채용면역조화법검측유선침윤성도관암조직석사절편중ALDH1여BCRP적표체，연구병탐토타문여림상병리특정적관계이급량자표체지간시부유상관성。결과：ALDH1、BCRP재유선암급암방유선조직중표체차이유통계학의의(χ2=14.685，P=0.000；χ2=12.243，P=0.000)。ALDH1적표체여환자년령、병리분기、액와림파결전이、조직학분급급자격소수체(estrogen receptor，ER)、잉격소수체(progesterone receptor，PR)、인류표피생장인자수체(human epidermal growth factor receptor，HER-2)상태균무관(P>0.05)；BCRP적표체여HER-2고표체유관，HER-2고표체조적암조직중BCRP양성표체솔교고，차이유통계학의의(χ2＝5.289，P＝0.021)。BCRP적표체여환자년령、종류분화정도、액와림파결전이、병리분기급ER、PR상태무관(P>0.05)；유선암종류간세포표지물ALDH1여BCRP무상관성(r=-0.039，P=0.786)。결론：ALDH1가능시구별우기타내약단백적일충독립적생물학인자，삼여유선암적화료내약혹종류적침습、전이등악성생물학행위。
Background and purpose:Resistance to antitumor agents is a major cause of treatment failure in patients with breast cancer. Research has shown that, tumor stem cell marker aldehyde dehydrogenase 1 (ALDH1) is related with some anticancer drugs (such as cyclophosphamide, cisplatin) resistance, and the content of ALDH1 in tumor cells after treatment is higher than that before treatment. Breast cancer resistance protein (BCRP) is not expressed in normal tissues, but high expressed in breast cancer of after treatment, it may be associated with the mechanism of tumor drug resistance. This study was to investigate the correlation between expression and the relationship between these two kinds of protein ALDH1, BCRP and clinical pathological characteristics. Methods:Immunohistochemistry was performed to detect the expression of ALDH1 and BCRP in breast inifltrating ductal carcinoma tissues, and whether there is a correlation between and explore their relationship with clinical pathological features and their expression. Results:The expression of ALDH1 protein and BCRP protein in breast cancer and paracarcinoma breast tissues has signiifcant difference(χ2=14.685, P=0.000;χ2=12.243, P=0.000).The expression of ALDH1 with patients age, pathologic stage, axillary lymph node metastasis, histological grading, ER, PR, and HER-2 state were not relevant(P>0.05). HER-2, BCRP protein, expression was higher in cancer tissue (χ2=5.289, P=0.021). There were no relevant with the expression of BCRP with patients age, pathologic stage, axillary lymph node metastasis and histological grading, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER-2) (P>0.05). Conclusion:ALDH1 proteins may be an independent factor compared with occur drug resistant protein, and participate breast cancer drug resistance in the chemotherapy and tumor invasion and metastasis of malignant biological behavior.