PROGNOSTIC VALUE OF PIK3CA MUTATION STATUS, PTEN AND ANDROGEN RECEPTOR EXPRESSION FOR METASTASIS-FREE SURVIVAL IN HER2-POSITIVE BREAST CANCER PATIENTS TREATED WITH TRASTUZUMAB IN ADJUVANT SETTING
PROGNOSTIC VALUE OF PIK3CA MUTATION STATUS, PTEN AND ANDROGEN RECEPTOR EXPRESSION FOR METASTASIS-FREE SURVIVAL IN HER2-POSITIVE BREAST CANCER PATIENTS TREATED WITH TRASTUZUMAB IN ADJUVANT SETTING
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DOI：
10.5114/pjp.2015.53009
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发表时间：
2015-06-01
影响因子：
0.8
通讯作者：
Jakubowicz, Jerzy
中科院分区：
文献类型：
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作者：
Adamczyk, Agnieszka;Niemiec, Joanna;Jakubowicz, Jerzy
HER2过表达乳腺癌患者对曲妥珠单抗的耐药性与进展或癌症死亡的风险较高相关，可能与PI3K/AKT/mTOR和Ras/Raf/MAPK信号通路的激活及其抑制物(PTEN)水平降低有关。HER2过表达乳腺癌患者(n=75)接受根治性局部治疗和辅助性环境下的曲妥珠单抗治疗。从石蜡切片中提取脱氧核糖核酸，用定量聚合酶链式反应技术检测PIK3CA基因(p.H1047R和p.E545K突变)的突变状态。免疫组织化学方法检测ER、PgR、AR、Ki-67、EGFR蛋白的表达，发现在EGFR阳性的癌组织中Ki-67LI显著升高(p=0.048)。此外，在低级别(G1/G2)癌以及雌孕激素和雄激素受体免疫阳性的肿瘤中，EGFR免疫阴性的发生率较高(p=0.042，p=0.016，p=0.044)。PN0和pN1(vs.pn2+3)分期(p=0.040)和Ki-67LI低(50%)的患者有良好的无转移生存期(p=0.014)。肿瘤雄激素受体免疫阴性(弱表达或不表达)或强表达的患者生存3年无转移(p=0.007)。我们的研究结果提示雄激素受体和抑癌基因状态可作为曲妥珠单抗敏感性的指标。
Resistance to trastuzumab in patients with HER2-overexpressing breast cancer is associated with higher risk of progression or cancer death, and might be related to activation of PI3K/AKT/mTOR and Ras/Raf/MAPK signaling cascades and a decreased level of their inhibitor (PTEN).HER2-overexpressing breast cancer patients (n = 75) treated with radical local therapy and trastuzumab in adjuvant setting were included into the study. Deoxyribonucleic acid isolated from paraffin sections was used to assess mutational status of the PIK3CA gene (p.H1047R and p.E545K mutations) by the quantitative polymerase chain reaction technique. Expression of selected proteins (ER, PgR, AR, Ki-67, EGFR) was assessed using immunohistochemistry.In the studied group we found significantly higher Ki-67LI in EGFR-positive carcinomas (p = 0.048). Moreover, EGFR immunonegativity was observed more frequently in low-grade (G1/G2) carcinomas as well as in estrogen/progesterone and androgen receptor immunopositive tumors (p = 0.042, p = 0.016, p = 0.044, respectively). Favorable metastasis-free survival was observed in patients with pN0 and pN1 (vs. pN2 + 3) stage (p = 0.040) and with tumors characterized by low Ki-67LI ( 50%) (p = 0.014). Patients with tumor androgen receptor immunonegativity (weak or lack of expression) or strong PTEN expression survived 3 years without metastases (p = 0.007).The results of our study suggest that androgen receptor and PTEN status might be considered as indicators of trastuzumab sensitivity.