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Open Access Research article

Copy Number Amplification of the PIK3CA Gene Is Associated with Poor Prognosis in Non-lymph node metastatic Head and Neck Squamous Cell Carcinoma

Toshihito Suda1, Takanori Hama12*, Shu Kondo3, Yuki Yuza4, Mamoru Yoshikawa1, Mitsuyoshi Urashima24, Takakuni Kato1 and Hiroshi Moriyama1

Author affiliations

1 Department of Oto-Rhino-Laryngology, Jikei University School of Medicine, 3-25-8 Nishi-shimbashi, Minato-ku, Tokyo, 105-8461, Japan

2 Division of Molecular Epidemiology, Jikei University School of Medicine, Minato-ku, Tokyo, Japan

3 Division of Invertebrate Genetics, National Institute of Genetics, Mishima, Japan

4 Department of Pediatrics, Jikei University School of Medicine, Minato-ku, Tokyo, Japan

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Citation and License

BMC Cancer 2012, 12:416  doi:10.1186/1471-2407-12-416

Published: 20 September 2012

Abstract

Background

Deregulation of the EGFR signaling pathway is one of the most frequently observed genetic abnormalities that drives cancer development. Although mutations in the downstream components of the EGFR signaling pathway, including KRAS, BRAF and PIK3CA, have been reported in numerous cancers, extensive mutation and copy number analysis of these genes in clinical samples has not been performed for head and neck squamous cell carcinoma (HNSCC).

Methods

We examined the mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients.

We used DNA sequencing to detect mutations and the copy number changes were evaluated by qPCR and array comparative genomic hybridization (CGH) analysis.

Results

We examined the mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients. We identified 3 mutations (2.6%) in K-RAS and 3 mutations (2.6%) in PIK3CA. Copy number amplification was found in 37 cases (32.2%) for PIK3CA, 10 cases (8.7%) for K-RAS and 2 cases (1.7%) for BRAF. Kaplan-Meier survival analysis revealed that copy-number amplification of PIK3CA was markedly associated with cancer relapse in patients without lymph node metastasis. (Log-rank test, p = 0.026)

Conclusions

Copy number amplification of the PIK3CA gene is associated with poor prognosis in HNSCC patients without lymph node metastasis. The PIK3CA copy number status will serve as a marker of poor prognosis in patients with HNSCC.

Keywords:
PIK3CA; KRAS; BRAF; Copy number analysis; Prognostic Factor