Skip to main content
Top
Published in: International Journal of Clinical Oncology 3/2013

01-06-2013 | Original Article

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

Authors: Satoshi Fujii, Hideoki Uryu, Ken Akashi, Kensuke Suzuki, Manabu Yamazaki, Makoto Tahara, Ryuichi Hayashi, Atsushi Ochiai

Published in: International Journal of Clinical Oncology | Issue 3/2013

Login to get access

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ferlay J, Shin HR, Bray F et al (2010) Estimates of worldwide burden of cancer in 2008. GLOBOCAN 2008. Int J Cancer 127:2893–2917PubMedCrossRef Ferlay J, Shin HR, Bray F et al (2010) Estimates of worldwide burden of cancer in 2008. GLOBOCAN 2008. Int J Cancer 127:2893–2917PubMedCrossRef
2.
go back to reference Diaz Jr EM, Sturges EM, Laramore GE (2003) Neoplasms of the head and neck. Holland JF, Frei E (eds) Cancer Medicine. BC Decker Inc., London, pp 1325–1371 Diaz Jr EM, Sturges EM, Laramore GE (2003) Neoplasms of the head and neck. Holland JF, Frei E (eds) Cancer Medicine. BC Decker Inc., London, pp 1325–1371
3.
go back to reference Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46:765–781PubMedCrossRef Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46:765–781PubMedCrossRef
4.
go back to reference Matsuda T, Marugame T, Kamo KI et al (2011) The Japan Cancer Surveillance Research Group. Cancer incidence and incidence rates in Japan in 2005: Based on data from 12 population-based cancer registries in the Monitoring of Cancer Incidence in Japan (MCIJ) Project. Jpn J Clin Oncol 41:139–147PubMedCrossRef Matsuda T, Marugame T, Kamo KI et al (2011) The Japan Cancer Surveillance Research Group. Cancer incidence and incidence rates in Japan in 2005: Based on data from 12 population-based cancer registries in the Monitoring of Cancer Incidence in Japan (MCIJ) Project. Jpn J Clin Oncol 41:139–147PubMedCrossRef
5.
go back to reference The Research Group for Population-based Cancer Registration in Japan (2004) Cancer incidence and incidence rates in Japan in 1999: estimates based on data from 11 population-based cancer registries. Jpn J Clin Oncol 34(6):352CrossRef The Research Group for Population-based Cancer Registration in Japan (2004) Cancer incidence and incidence rates in Japan in 1999: estimates based on data from 11 population-based cancer registries. Jpn J Clin Oncol 34(6):352CrossRef
6.
go back to reference Ohshima A et al (2004) Cancer statistics morbidity/death/prognosis 2004. Shinohara Shuppan Shinsha, Tokyo Ohshima A et al (2004) Cancer statistics morbidity/death/prognosis 2004. Shinohara Shuppan Shinsha, Tokyo
7.
go back to reference Iro H, Waldfahrer F (1998) Evaluation of the newly updated TNM classification of head and neck carcinoma with data from 3247 patients. Cancer 83:2201–2207PubMedCrossRef Iro H, Waldfahrer F (1998) Evaluation of the newly updated TNM classification of head and neck carcinoma with data from 3247 patients. Cancer 83:2201–2207PubMedCrossRef
8.
9.
go back to reference Argiris A, Bruce E (2004) Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemotherapy. Clin Cancer Res 10:1956–1962PubMedCrossRef Argiris A, Bruce E (2004) Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemotherapy. Clin Cancer Res 10:1956–1962PubMedCrossRef
10.
go back to reference Garrett CR, Eng C (2011) Cetuximab in the treatment of patients with colorectal cancer. Expert Opin Biol Ther 11(7):937–949PubMedCrossRef Garrett CR, Eng C (2011) Cetuximab in the treatment of patients with colorectal cancer. Expert Opin Biol Ther 11(7):937–949PubMedCrossRef
11.
go back to reference Jonker DJ, O’Callaghan CJ, Karapetis CS et al (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357(20):2040–2048PubMedCrossRef Jonker DJ, O’Callaghan CJ, Karapetis CS et al (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357(20):2040–2048PubMedCrossRef
12.
go back to reference Karapetis CS, Khambata-Ford S, Jonker DJ et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359(17):1757–1765PubMedCrossRef Karapetis CS, Khambata-Ford S, Jonker DJ et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359(17):1757–1765PubMedCrossRef
13.
go back to reference Carpenter G (1983) The biochemistry and physiology of the receptor-kinase for epidermal growth factor. Mol Cell Endocrinol 31:1–19PubMedCrossRef Carpenter G (1983) The biochemistry and physiology of the receptor-kinase for epidermal growth factor. Mol Cell Endocrinol 31:1–19PubMedCrossRef
14.
go back to reference Salomon DS, Brandt R, Ciardiello F et al (1995) Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19:183–232PubMedCrossRef Salomon DS, Brandt R, Ciardiello F et al (1995) Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19:183–232PubMedCrossRef
15.
go back to reference Mendelsohn J, Baselga J (2003) Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 21:2787–2799PubMedCrossRef Mendelsohn J, Baselga J (2003) Status of epidermal growth factor receptor antagonists in the biology and treatment of cancer. J Clin Oncol 21:2787–2799PubMedCrossRef
16.
go back to reference Mendelsohn J, Baselga J (2006) Epidermal growth factor receptor targeting in cancer. Semin Oncol 33(4):369–385PubMedCrossRef Mendelsohn J, Baselga J (2006) Epidermal growth factor receptor targeting in cancer. Semin Oncol 33(4):369–385PubMedCrossRef
17.
go back to reference Lockhart AC, Berlin JD (2005) The epidermal growth factor receptor as a target for colorectal cancer therapy. Semin Oncol 32(1):52–60PubMedCrossRef Lockhart AC, Berlin JD (2005) The epidermal growth factor receptor as a target for colorectal cancer therapy. Semin Oncol 32(1):52–60PubMedCrossRef
18.
go back to reference Steele RJ, Kelly P, Ellul B et al (1990) Epidermal growth factor receptor expression in colorectal cancer. Br J Surg 77(12):1352–1354PubMedCrossRef Steele RJ, Kelly P, Ellul B et al (1990) Epidermal growth factor receptor expression in colorectal cancer. Br J Surg 77(12):1352–1354PubMedCrossRef
19.
go back to reference Kluftinger AM, Robinson BW, Quenville NF et al (1992) Correlation of epidermal growth factor receptor and c-erbB2 oncogene product to known prognostic indicators of colorectal cancer. Surg Oncol 1(1):97–105PubMedCrossRef Kluftinger AM, Robinson BW, Quenville NF et al (1992) Correlation of epidermal growth factor receptor and c-erbB2 oncogene product to known prognostic indicators of colorectal cancer. Surg Oncol 1(1):97–105PubMedCrossRef
20.
go back to reference Chung CH, Ely K, McGavran L et al (2006) Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol 24:4170–4176PubMedCrossRef Chung CH, Ely K, McGavran L et al (2006) Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol 24:4170–4176PubMedCrossRef
21.
go back to reference Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351(4):337–345PubMedCrossRef Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351(4):337–345PubMedCrossRef
22.
go back to reference Sheikh Ali MA, Gunduz M, Nagatsuka H et al (2008) Expression and mutation analysis of epidermal growth factor receptor in head and neck squamous cell carcinoma. Cancer Sci 99(8):1589–1594PubMedCrossRef Sheikh Ali MA, Gunduz M, Nagatsuka H et al (2008) Expression and mutation analysis of epidermal growth factor receptor in head and neck squamous cell carcinoma. Cancer Sci 99(8):1589–1594PubMedCrossRef
23.
go back to reference Karapetis CS, Khambata-Ford S, Jonker DJ et al (2004) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. J Histochem Cytochem 52(7):893–901CrossRef Karapetis CS, Khambata-Ford S, Jonker DJ et al (2004) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. J Histochem Cytochem 52(7):893–901CrossRef
24.
go back to reference Atkins D, Reiffen KA, Tegtmeier CL et al (2008) Immunohistochemical detection of EGFR in paraffin-embedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J Histochem Cytochem 52(7):893–901CrossRef Atkins D, Reiffen KA, Tegtmeier CL et al (2008) Immunohistochemical detection of EGFR in paraffin-embedded tumor tissues: variation in staining intensity due to choice of fixative and storage time of tissue sections. J Histochem Cytochem 52(7):893–901CrossRef
25.
go back to reference Japanese Society of Medical Oncology (2009) Clinical oncology update-essentials for medical oncologists, 2nd edn. Nankodo, Tokyo Japanese Society of Medical Oncology (2009) Clinical oncology update-essentials for medical oncologists, 2nd edn. Nankodo, Tokyo
26.
go back to reference Dahabreh IJ, Terasawa T, Castaldi PJ et al (2011) Systematic review: anti-epidermal growth factor receptor treatment effect. Ann Intern Med 154(1):37–49PubMedCrossRef Dahabreh IJ, Terasawa T, Castaldi PJ et al (2011) Systematic review: anti-epidermal growth factor receptor treatment effect. Ann Intern Med 154(1):37–49PubMedCrossRef
27.
go back to reference Weber A, Langhanki L, Sommerer F et al (2003) Mutations of the BRAF gene in squamous cell carcinoma of the head and neck. Oncogene 22(30):4757–4759PubMedCrossRef Weber A, Langhanki L, Sommerer F et al (2003) Mutations of the BRAF gene in squamous cell carcinoma of the head and neck. Oncogene 22(30):4757–4759PubMedCrossRef
28.
go back to reference Van Damme N, Deron P, Van Roy N et al (2010) Epidermal growth factor receptor and K-RAS status in two cohorts of squamous cell carcinomas 10:189 Van Damme N, Deron P, Van Roy N et al (2010) Epidermal growth factor receptor and K-RAS status in two cohorts of squamous cell carcinomas 10:189
29.
go back to reference Hama T, Kato T (2010) Molecular targeted therapy for EGFR and VEGF in head and neck squamous cell carcinomas. Toukeibu-Gan 36(4):436–441CrossRef Hama T, Kato T (2010) Molecular targeted therapy for EGFR and VEGF in head and neck squamous cell carcinomas. Toukeibu-Gan 36(4):436–441CrossRef
30.
go back to reference Scartozzi M, Bearzi I, Mandolesi A et al (2009) Epidermal growth factor receptor (EGFR) gene copy number (GCN) correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH) and chromogenic in situ hybridization (CISH) analysis. BMC Cancer 9:303PubMedCrossRef Scartozzi M, Bearzi I, Mandolesi A et al (2009) Epidermal growth factor receptor (EGFR) gene copy number (GCN) correlates with clinical activity of irinotecan-cetuximab in K-RAS wild-type colorectal cancer: a fluorescence in situ (FISH) and chromogenic in situ hybridization (CISH) analysis. BMC Cancer 9:303PubMedCrossRef
31.
go back to reference Szabó B, Nelhűbel GA, Kárpáti A et al (2011) Clinical significance of genetic alterations and expression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas. Oral Oncol 47(6):487–496PubMedCrossRef Szabó B, Nelhűbel GA, Kárpáti A et al (2011) Clinical significance of genetic alterations and expression of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas. Oral Oncol 47(6):487–496PubMedCrossRef
32.
go back to reference Sharafinski ME, Ferris RL, Ferrone S et al (2010) Epidermal growth factor receptor targeted therapy of squamous cell carcinoma of the head and neck. Head Neck 32(10):1412–1421PubMedCrossRef Sharafinski ME, Ferris RL, Ferrone S et al (2010) Epidermal growth factor receptor targeted therapy of squamous cell carcinoma of the head and neck. Head Neck 32(10):1412–1421PubMedCrossRef
33.
go back to reference Ang KK, Berkey BA, Tu X et al (2002) Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 62(24):7350–7356PubMed Ang KK, Berkey BA, Tu X et al (2002) Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 62(24):7350–7356PubMed
Metadata
Title
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
Authors
Satoshi Fujii
Hideoki Uryu
Ken Akashi
Kensuke Suzuki
Manabu Yamazaki
Makoto Tahara
Ryuichi Hayashi
Atsushi Ochiai
Publication date
01-06-2013
Publisher
Springer Japan
Published in
International Journal of Clinical Oncology / Issue 3/2013
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-012-0402-z

Other articles of this Issue 3/2013

International Journal of Clinical Oncology 3/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine