磷酸化AKT在早期乳腺癌中的表达模式及预测价值

Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer.

作者信息

Andre F, Nahta R, Conforti R, Boulet T, Aziz M, Yuan L X H, Meslin F, Spielmann M, Tomasic G, Pusztai L, Hortobagyi G N, Michiels S, Delaloge S, Esteva F J

机构信息

Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.

出版信息

Ann Oncol. 2008 Feb;19(2):315-20. doi: 10.1093/annonc/mdm429. Epub 2007 Sep 5.

DOI:10.1093/annonc/mdm429

PMID:17804473

Abstract

BACKGROUND

AKT phosphorylation is a critical step in the activation of growth factor receptors and can mediate tumor resistance to anthracyclines. We evaluated the expression patterns and predictive value of phosphorylated AKT (pAKT) in breast cancer tissues.

PATIENTS AND METHODS

pAKT expression was assessed by immunohistochemistry in 823 tumors from patients with early breast cancer enrolled in two randomized trials. The distribution of pAKT expression was correlated with HER2 and epidermal growth factor receptor (EGFR) expression. The predictive value of pAKT for the efficacy of adjuvant chemotherapy was determined by test for interaction.

RESULTS

pAKT, EGFR, and HER2 were expressed in 119 of 781 (15%), 118 of 758 (16%), and 99 of 775 (13%) assessable tumors. Staining was positive for pAKT in 28 of 99 (28%) and 90 of 676 (13%) HER2+ and HER2- tumors (P < 0.001). pAKT was expressed in 15 of 94 (16%) and 75 of 563 (13%) HER2-/EGFR+ and HER2-/EGFR- tumors, respectively (P = 0.49). A positive staining for pAKT did not correlate with prognosis (P = 0.94), and did not predict the resistance to anthracyclines (test for interaction, P = 0.70).

CONCLUSIONS

AKT phosphorylation is associated with HER2 expression but not EGFR expression in patients with early breast cancer. pAKT is not predictive for the efficacy of anthracycline-based adjuvant chemotherapy.

摘要

背景

AKT磷酸化是生长因子受体激活的关键步骤，可介导肿瘤对蒽环类药物的耐药性。我们评估了磷酸化AKT（pAKT）在乳腺癌组织中的表达模式及预测价值。

患者与方法

通过免疫组化法评估了两项随机试验中823例早期乳腺癌患者肿瘤组织中的pAKT表达情况。pAKT表达分布与HER2及表皮生长因子受体（EGFR）表达相关。通过交互作用检验确定pAKT对辅助化疗疗效的预测价值。

结果

在781例可评估肿瘤中的119例（15%）、758例中的118例（16%）以及775例中的99例（13%）中分别检测到pAKT、EGFR和HER2表达。在HER2阳性和HER2阴性肿瘤中，pAKT染色阳性的分别有99例中的28例（28%）和676例中的90例（13%）（P<0.001）。在HER2阴性/EGFR阳性和HER2阴性/EGFR阴性肿瘤中，pAKT表达的分别有94例中的15例（16%）和563例中的75例（13%）（P = 0.49）。pAKT染色阳性与预后无关（P = 0.94），也不能预测对蒽环类药物的耐药性（交互作用检验，P = 0.70）。