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Clinical significance of KRAS gene mutation and epidermal growth factor receptor expression in Japanese patients with squamous cell carcinoma of the larynx, oropharynx and hypopharynx

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Abstract

Purpose

The significance of epidermal growth factor receptor (EGFR) signaling has been recognized in various cancers and anti-EGFR therapies in Japan are currently under consideration in squamous cell carcinoma of the head and neck (SCCHN) similar to colorectal cancer. However, there was no established survey regarding heterogeneous EGFR protein expression in Japanese SCCHN patients. The purpose of this study is to examine the relationship between EGFR expression or KRAS mutation (related to the alteration of EGFR pathway) and the clinicopathological characteristics of SCCHN.

Materials and methods

We retrospectively examined the expression of EGFR protein by immunohistochemistry and KRAS gene mutation at codons 12 and 13 by using paraffin-embedded and formalin-fixed primary tumor tissues from 205 patients with SCCHN who underwent surgery at National Cancer Center Hospital East.

Results

In 200 of the 205 patients (97.6 %), EGFR protein was expressed despite intratumoral heterogeneity. No patients had KRAS mutation at codons 12 or 13, and all 183 tumors showed wild-type KRAS. Positive rate of EGFR protein expression was significantly associated with better disease free survival (DFS) (P = 0.0471) and the intensity of EGFR protein expression showed a tendency for better DFS (P = 0.1034). Both higher EGFR positive rate and more intense EGFR expression were significantly associated with well differentiated subtype of squamous cell carcinoma (P = 0.0003 and P = 0.0007, respectively).

Conclusion

Most SCCHN patients may be good candidates for the anti-EGFR therapies.

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Acknowledgments

We thank Mr. Shinya Yanagi, Mr. Takuya Aiba and Ms. Mari Takahashi for preparing tissue thin sections for genomic DNA extraction and immunohistochemistry, Mr. Masaya Mizushima, Mr. Yoshiteru Ishikawa and Ms. Naomi Komatsuzaki from Merck Serono Co., Ltd. for secretarial assistance.

Conflict of interest

This work was supported by a research grant from MerckSerono Co. and reviewed by Merck Serono.

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Authors and Affiliations

  1. Pathology Division, Research Center for Innovative Oncology, National Cancer Center at Kashiwa, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Satoshi Fujii, Manabu Yamazaki & Atsushi Ochiai

  2. Department of Head and Neck Surgery, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Hideoki Uryu, Ken Akashi, Kensuke Suzuki & Ryuichi Hayashi

  3. Department of Head and Neck Medicine, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan

    Makoto Tahara

  4. Division of Oral Pathology, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Manabu Yamazaki

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  1. Satoshi Fujii
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  2. Hideoki Uryu
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Corresponding author

Correspondence to Atsushi Ochiai.

Electronic supplementary material

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10147_2012_402_MOESM1_ESM.ppt

Supplementary Fig. 1 Relationship between tumor differentiation and OS or DFS in each tumor site (A,B) Larynx (C,D) Oropharynx (E,F) Hypopharynx (PPT 171 kb)

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Fujii, S., Uryu, H., Akashi, K. et al. Clinical significance of KRAS gene mutation and epidermal growth factor receptor expression in Japanese patients with squamous cell carcinoma of the larynx, oropharynx and hypopharynx. Int J Clin Oncol 18, 454–463 (2013). https://doi.org/10.1007/s10147-012-0402-z

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  • DOI: https://doi.org/10.1007/s10147-012-0402-z

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