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PIK3CA mutation is associated with a favorable prognosis among patients with curatively resected esophageal squamous cell carcinoma.
Clin Cancer Res. 2013 May 01; 19(9):2451-9.CC

Abstract

PURPOSE

PIK3CA encodes the catalytic subunit of PI3K, p110α. 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.

Authors+Show Affiliations

Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23532889

Citation

Shigaki, Hironobu, et al. "PIK3CA Mutation Is Associated With a Favorable Prognosis Among Patients With Curatively Resected Esophageal Squamous Cell Carcinoma." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 19, no. 9, 2013, pp. 2451-9.
Shigaki H, Baba Y, Watanabe M, et al. PIK3CA mutation is associated with a favorable prognosis among patients with curatively resected esophageal squamous cell carcinoma. Clin Cancer Res. 2013;19(9):2451-9.
Shigaki, H., Baba, Y., Watanabe, M., Murata, A., Ishimoto, T., Iwatsuki, M., Iwagami, S., Nosho, K., & Baba, H. (2013). PIK3CA mutation is associated with a favorable prognosis among patients with curatively resected esophageal squamous cell carcinoma. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 19(9), 2451-9. https://doi.org/10.1158/1078-0432.CCR-12-3559
Shigaki H, et al. PIK3CA Mutation Is Associated With a Favorable Prognosis Among Patients With Curatively Resected Esophageal Squamous Cell Carcinoma. Clin Cancer Res. 2013 May 1;19(9):2451-9. PubMed PMID: 23532889.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PIK3CA mutation is associated with a favorable prognosis among patients with curatively resected esophageal squamous cell carcinoma. AU - Shigaki,Hironobu, AU - Baba,Yoshifumi, AU - Watanabe,Masayuki, AU - Murata,Asuka, AU - Ishimoto,Takatsugu, AU - Iwatsuki,Masaaki, AU - Iwagami,Shiro, AU - Nosho,Katsuhiko, AU - Baba,Hideo, Y1 - 2013/03/26/ PY - 2013/3/28/entrez PY - 2013/3/28/pubmed PY - 2013/11/13/medline SP - 2451 EP - 9 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin Cancer Res VL - 19 IS - 9 N2 - PURPOSE: PIK3CA encodes the catalytic subunit of PI3K, p110α. 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. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/23532889/PIK3CA_mutation_is_associated_with_a_favorable_prognosis_among_patients_with_curatively_resected_esophageal_squamous_cell_carcinoma_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=23532889 DB - PRIME DP - Unbound Medicine ER -