PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma

Hyo Song Kim, Seung Eun Lee, Yoon Sung Bae, Dae Joon Kim, Chang Geol Lee, Jin Hur, Hyunsoo Chung, Jun Chul Park, Sung Kwan Shin, Sang Kil Lee, Yong Chan Lee, Hye Ryun Kim, Young Mog Shim, Susan S. Jewell, Hyunki Kim, Yoon La Choi, Byoung Chul Cho

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7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)30691-30701
Number of pages11
JournalOncotarget
Volume7
Issue number21
DOIs
Publication statusPublished - 2016 May 24

All Science Journal Classification (ASJC) codes

  • Oncology

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    Kim, H. S., Lee, S. E., Bae, Y. S., Kim, D. J., Lee, C. G., Hur, J., Chung, H., Park, J. C., Shin, S. K., Lee, S. K., Lee, Y. C., Kim, H. R., Shim, Y. M., Jewell, S. S., Kim, H., Choi, Y. L., & Cho, B. C. (2016). PIK3CA amplification is associated with poor prognosis among patients with curatively resected esophageal squamous cell carcinoma. Oncotarget, 7(21), 30691-30701. https://doi.org/10.18632/oncotarget.8749