PIK3CA Mutation Is Associated with a Favorable Prognosis among Patients with Curatively Resected Esophageal Squamous Cell Carcinoma
PIK3CA Mutation Is Associated with a Favorable Prognosis among Patients with Curatively Resected Esophageal Squamous Cell Carcinoma
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DOI：
10.1158/1078-0432.ccr-12-3559
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发表时间：
2013-05-01
影响因子：
11.5
通讯作者：
Baba, Hideo
中科院分区：
文献类型：
--
作者：
Shigaki, Hironobu;Baba, Yoshifumi;Baba, Hideo
目的：PIK 3CA编码PI 3 K的催化亚基p110 α。突变体PIK 3CA刺激AKT通路并促进癌细胞增殖。PIK 3CA突变与结直肠癌或肺癌患者的不良预后相关。相比之下，PIK 3CA突变和有利的乳腺癌之间的关系已经在乳腺癌中显示。然而，PIK 3CA突变对食管鳞状细胞癌（ESCC）患者的预后的影响仍然不清楚。实验设计：使用219个治愈性切除的ESCC和8个食管癌细胞系的非偏倚数据库，我们评估PIK 3CA突变状态焦磷酸测序。p53和磷酸化AKT的表达（即，结果：46例（21%）PIK 3CA基因第9和/或第20外显子突变。没有ESCC细胞系携带PIK 3CA突变。PIK 3CA突变与磷酸化AKT表达显著相关，但与p53表达、性别、手术年龄、吸烟、饮酒或组织学分级无关。与野生型PIK 3CA病例相比，在外显子9和/或20中具有PIK 3CA突变的患者经历了显著更好的无病生存期[对数秩P = 0.0089;单变量HR：0.37，95%置信区间（CI）：0.15-0.75，P = 0.0042;多变量HR：0.34，95% CI：0.15-0.75，P = 0.0042]。0.10-0.86，P = 0.021]和总生存期（对数秩P = 0.012;单变量HR：0.38，95% CI：0.16-0.78，P = 0.0060;多变量HR：0.35，95% CI：0.10-0.90，P = 0.028）。ESCC中的PIK 3CA突变与更长的生存期相关，表明其作为预后生物标志物的作用。未来的研究需要证实这种关联，并阐明PIK 3CA突变影响肿瘤行为的确切机制。临床癌症研究; 19（9）; 2451-9。(C)2013年AACR。
Purpose: PIK3CA encodes the catalytic subunit of PI3K, p110 alpha. Mutant PIK3CA stimulates the AKT pathway and promotes cancer cell proliferation. PIK3CA mutations have been associated with poor prognosis in patients with colorectal or lung cancer. In contrast, the relationship between PIK3CA mutations and favorable prognoses has been shown in breast cancer. However, the influence of PIK3CA mutations on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) remains unclear.Experimental Design: Using a nonbiased database of 219 curatively resected ESCCs and eight esophageal cancer cell lines, we evaluated PIK3CA mutational status by pyrosequencing. The expression of p53 and phosphorylated AKT (i.e., AKT activation) was evaluated by immunohistochemistry.Results: PIK3CA mutations in exon 9 and/or 20 were detected in 46 cases (21%). No ESCC cell line harbored PIK3CA mutations. PIK3CA mutations were significantly associated with phosphorylated AKT expression, but not with p53 expression, sex, age at surgery, tobacco use, alcohol use, or histologic grade. Compared with wild-type PIK3CA cases, patients with PIK3CA mutations in exons 9 and/or 20 experienced significantly better disease-free survival [log-rank P = 0.0089; univariate HR: 0.37, 95% confidence interval (CI): 0.15-0.75, P = 0.0042; multivariate HR: 0.34, 95% CI: 0.10-0.86, P = 0.021] and overall survival (log-rank P = 0.012; univariate HR: 0.38, 95% CI: 0.16-0.78, P = 0.0060; multivariate HR: 0.35, 95% CI: 0.10-0.90, P = 0.028).Conclusion: PIK3CA mutations in ESCC are associated with longer survival, suggesting its role as a prognostic biomarker. Future studies are needed to confirm this association and to elucidate the exact mechanisms by which PIK3CA mutations affect tumor behavior. Clin Cancer Res; 19(9); 2451-9. (C) 2013 AACR.