PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma.
PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma.
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DOI：
10.18632/oncotarget.8749
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发表时间：
2016-05-24
期刊：
影响因子：
--
通讯作者：
Cho BC
中科院分区：
文献类型：
--
作者：
Kim HS;Lee SE;Bae YS;Kim DJ;Lee CG;Hur J;Chung H;Park JC;Shin SK;Lee SK;Lee YC;Kim HR;Shim YM;Jewell SS;Kim H;Choi YL;Cho BC
目的探讨食管鳞状细胞癌（ESCC）患者PIK 3CA基因扩增的临床病理特征及其对预后的影响。应用荧光原位杂交技术检测534例食管鳞癌组织中PIK 3CA基因拷贝数。PIK 3CA扩增定义为PIK 3CA/着丝粒3比值≥ 2.0或PIK 3CA信号/肿瘤细胞核的平均数≥ 5.0。在388例病例中，通过直接测序评估了编码高度保守的螺旋和激酶结构域的外显子9和20中的PIK 3CA突变。PIK 3CA扩增56例（10.5%）。PIK 3CA扩增与较高的T分期（P=0.026）和病理分期（P=0.053）显著相关。PIK 3CA扩增组的无病生存期（DFS）明显短于非扩增组（33.4 vs 63.1个月，P=0.019）。在调整性别、肿瘤位置、病理分期、组织学分级和辅助治疗后，PIK 3CA扩增与较短DFS显著相关（调整后风险比[AHR] 1.53; 95%CI，1.10-2.17; P=0.02）。PIK 3CA扩增组的生存期有缩短的趋势（52.1个月vs 96.5个月，P=0.116）。在388例病例中，6例（1.5%）检测到PIK 3CA突变; 5例E545 K外显子9突变，1例H1047 L外显子20突变。PIK 3CA扩增是一种常见的致癌改变，与较短的生存期相关，表明其作为切除的ESCC的预后生物标志物的作用。PIK 3CA扩增可能是ESCC的一个有希望的治疗靶点。
To investigate the clinicopathologic characteristics and the prognostic impact of PIK3CA gene amplification in curatively resected esophageal squamous cell carcinoma (ESCC). Using 534 curatively resected ESCCs, the PIK3CA gene copy number was evaluated with fluorescent in situ hybridization. PIK3CA amplification was defined as PIK3CA/centromere 3 ratio is ≥ 2.0 or average number of PIK3CA signals/tumor cell nucleus ≥ 5.0. PIK3CA mutations in exon 9 and 20, encoding the highly conserved helical and kinase domains were assessed by direct sequencing in 388 cases. PIK3CA amplification was detected in 56 (10.5%) cases. PIK3CA amplification was significantly associated with higher T-stage (P=0.026) and pathologic stage (P=0.053). PIK3CA amplification showed a significantly shorter disease free survival (DFS) compared with that of non-amplified group (33.4 vs 63.1 months, P=0.019). After adjusting for gender, tumor location, pathologic stage, histologic grade and adjuvant treatment, PIK3CA amplification was significantly associated with a shorter DFS (adjusted hazard ratio [AHR] 1.53; 95% CI, 1.10-2.17; P=0.02). Though the statistical insignificance, PIK3CA amplification showed tendency of shorter OS (52.1 vs 96.5 moths, P=0.116). PIK3CA mutations were detected in 6 (1.5%) of 388 cases; 5 cases with exon 9 mutations in E545K while one exon 20 mutation in H1047L. PIK3CA amplification is a frequent oncogenic alteration and associated with shorter survival, suggesting its role as a prognostic biomarker in resected ESCC. PIK3CA amplification may represent a promising therapeutic target for ESCC.
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影响因子：
2.2
作者：
Mori, Ryota;Ishiguro, Hideyuki;Kuwabara, Yoshiyuki
通讯作者：
Kuwabara, Yoshiyuki
DOI：
10.1158/1078-0432.ccr-14-0947
发表时间：
2015-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Sarker D;Ang JE;Baird R;Kristeleit R;Shah K;Moreno V;Clarke PA;Raynaud FI;Levy G;Ware JA;Mazina K;Lin R;Wu J;Fredrickson J;Spoerke JM;Lackner MR;Yan Y;Friedman LS;Kaye SB;Derynck MK;Workman P;de Bono JS
通讯作者：
de Bono JS
影响因子：
4.3
作者：
Samuels, Y;Velculescu, VE
通讯作者：
Velculescu, VE
影响因子：
11.5
作者：
Shigaki, Hironobu;Baba, Yoshifumi;Baba, Hideo
通讯作者：
Baba, Hideo
影响因子：
5
作者：
Brown, LM;Hoover, R;Fraumeni, JF
通讯作者：
Fraumeni, JF