摘要
目的探讨人类表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)阳性乳腺癌患者应用酪氨酸激酶抑制剂治疗后肿瘤组织和血清增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)表达变化及PCNA与疗效的关系。方法初次就诊的HER-2阳性(局部)晚期乳腺癌患者47例,应用拉帕替尼(1250 mg/次,1次/d,21 d为1个周期)或吡咯替尼(400 mg/次,1次/d,21 d为1个周期)进行治疗,分别于靶向治疗前及治疗2、4、6个周期后取肿瘤组织及血清标本。采用实时荧光定量PCR法检测肿瘤组织PCNA mRNA相对表达量,采用免疫组织化学法检测肿瘤组织PCNA蛋白阳性表达情况,采用ELISA法检测血清PCNA表达水平,并进行治疗前、后比较;比较PCNA阳性表达与阴性表达患者的治疗有效率。结果治疗2、4、6个周期肿瘤组织PCNA mRNA相对表达量(1.494±0.141、1.348±0.167、1.263±0.205)依次降低(P<0.05),治疗4、6个周期低于治疗前(1.557±0.221)(P<0.05);治疗6个周期肿瘤组织PCNA蛋白阳性表达率(40.43%)低于治疗前(70.21%)和治疗2个周期(61.70%)(P<0.05),与治疗4个周期(51.06%)比较差异无统计学意义(P>0.05);治疗4、6个周期血清PCNA[(298.787±85.683)、(262.963±109.312)ng/L]较治疗前[(390.298±113.056)ng/L]和治疗2个周期[(355.915±93.621)ng/L]降低(P<0.05),治疗2个周期与治疗前、治疗4个周期与治疗6个周期比较差异无统计学意义(P>0.05)。治疗前PCNA蛋白阳性表达者的治疗有效率(84.85%)高于PCNA蛋白阴性表达者(21.43%)(P<0.05)。结论酪氨酸激酶抑制剂可降低PCNA的表达,降低HER-2阳性乳腺癌细胞的增殖能力,PCNA阳性表达的HER-2阳性晚期乳腺癌患者临床治疗有效率更高。
Objective To investigate the change of proliferating cell nuclear antigen(PCNA) in tumor tissue and serum of patients with human epidermal growth factor receptor-2(HER-2) positive breast cancer after treatment with tyrosine kinase inhibitor, and the correlation of PCNA with the therapeutic effect. Methods Forty-seven patients with local HER-2 positive advanced breast cancer at initial visit were treated with lapatinib(1 250 mg, once a day, 21 days as a cycle) or pyrrolidine(400 mg, once a day, 21 days as a cycle). The tumor tissue and serum samples were collected before and after 2, 4 and 6 cycles of targeted therapy. The relative expression of PCNA mRNA was detected by real-time fluorescence quantitative PCR. The positive expression of PCNA protein was detected by immunohistochemistry. The expression of serum PCNA was detected by ELISA. The differences of expression were compared before and after treatment. The effective rates were compared between the patients with positive and negative expression of PCNA. Results The relative expression of PCNA mRNA in tumor tissue decreased gradually after 2, 4 and 6 cycles of treatment in turn(1.494±0.141, 1.348±0.167, 1.263±0.205)(P<0.05), and was lower after 4 and 6 cycles of treatment than that before treatment(1.557±0.221)(P<0.05). The positive rate of PCNA protein in tumor tissue was lower after 6 cycles of treatment(40.43%) than that before treatment(70.21%) and after 2 cycles of treatment(61.70%)(P<0.05), and showed no significant difference compared with that after 4 cycles of treatment(51.06%)(P>0.05).The serum PCNA level was lower after 4 and 6 cycles of treatment((298.787±85.683),(262.963±109.312)ng/L)than that before treatment and 2 cycles of treatment((390.298±113.056),(355.915±93.621)ng/L)(P<0.05),and showed no significant differences after 2 cycles of treatment compared with that before treatment(P>0.05)as well as after 4 cycles of treatment compared with that after 6 cycles of treatment(P>0.05).The effective rate was higher in PCNA positive patients(8
作者
巫姜
杨玉庆
孟小玉
孟庆杰
樊菁
王廷
李南林
WU Jiang;YANG Yuqing;MENG Xiaoyu;MENG Qingjie;FAN Jing;WANG Ting;LI Nanlin(Department of Vascular Surgery and Th yroid-Breast Surgery,the First Affiliated Hosiptal of Air Force Medical Universit y,Xi'an 710032,China;Department of General Surgery,Tongchuan People's Hospital,Tongchuan 727100,China;Department of Thyroid and Breast Surgery the Third Hos pital of Xi'an,Affiliated Hospital of Northwest University,Xi'an 710021,China)
出处
《中华实用诊断与治疗杂志》
2020年第10期1057-1060,共4页
Journal of Chinese Practical Diagnosis and Therapy
基金
国家自然科学基金(81472598)
CSCO基金项目(Y-HR2018-252)。
关键词
乳腺癌
酪氨酸激酶抑制剂
人表皮生长因子受体-2
增殖细胞核抗原
breast cancer
tyrosine kinase inhibitor
human epidermal growth factor receptor-2
proliferating cell nuclear antigen
