Division of Medical Oncology, Regina Elena Cancer Institute, Rome, Italy.
Oncology. 2010;78(2):141-9. doi: 10.1159/000312656. Epub 2010 Apr 13.
The phosphatase and tensine homologue gene (PTEN) plays a crucial role in proliferation and survival of cancer cells by antagonizing the function of phosphatidylinositol 3'-kinase (PI3K), which, in turn, results in decreased Akt activity. We investigated the clinical impact of the expression of PTEN, p-Akt and PI3K in HER2-positive metastatic breast cancer (MBC) patients treated with trastuzumab-based therapies.
Seventy-three patients treated with trastuzumab-based therapies were included and followed prospectively. PTEN, p-Akt and PI3K expression was determined by immunohistochemistry.
PTEN, p-Akt and PI3K resulted positive in 48%, 71% and 46.5% of patients, respectively. A significant correlation between PTEN and p-Akt (kappa 0.22, p = 0.03) and p-Akt and PI3K (kappa 0.20, p = 0.05) was observed. PTEN-positive patients had a progression-free survival (PFS) longer than PTEN-negative ones (p = 0.06). When grouped together, patients co-expressing PTEN and p-Akt had a statistically significant longer PFS as compared to the rest of patients (p = 0.01). At the multivariate analysis, PTEN and p-Akt co-expression was an independent predictor of lower risk of progression (hazard ratio 0.53, p = 0.05).
In HER2-positive MBC, basal co-expression of PTEN and p-Akt might identify those patients who are more likely to benefit from trastuzumab-based therapies.
磷酸酶和张力蛋白同源物基因（PTEN）通过拮抗磷脂酰肌醇 3'-激酶（PI3K）的功能在癌细胞的增殖和存活中发挥关键作用，从而导致 Akt 活性降低。我们研究了在接受曲妥珠单抗为基础的治疗的 HER2 阳性转移性乳腺癌（MBC）患者中，PTEN、p-Akt 和 PI3K 的表达对临床的影响。
纳入 73 例接受曲妥珠单抗为基础的治疗的患者进行前瞻性随访。通过免疫组织化学法检测 PTEN、p-Akt 和 PI3K 的表达。
PTEN、p-Akt 和 PI3K 的阳性率分别为 48%、71%和 46.5%。PTEN 与 p-Akt（kappa 0.22，p = 0.03）以及 p-Akt 与 PI3K（kappa 0.20，p = 0.05）之间存在显著相关性。PTEN 阳性患者的无进展生存期（PFS）长于 PTEN 阴性患者（p = 0.06）。当联合分组时，PTEN 和 p-Akt 共同表达的患者的 PFS 明显长于其他患者（p = 0.01）。在多变量分析中，PTEN 和 p-Akt 共同表达是疾病进展风险降低的独立预测因素（风险比 0.53，p = 0.05）。
在 HER2 阳性 MBC 中，PTEN 和 p-Akt 的基础共表达可能可以识别出那些更有可能从曲妥珠单抗为基础的治疗中获益的患者。
