EGFR and K-ras gene mutation status in squamous cell anal carcinoma: A role for concurrent radiation and EGFR inhibitors

A. Paliga, R. Onerheim, A. Gologan, G. Chong, A. Spatz, T. Niazi, A. Garant, D. MacHeto, T. Alcindor, T. Vuong

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Background:There is a growing appreciation for radio-sensitiser use in multi-modal cancer treatment models. Squamous cell anal carcinoma (SCAC) is a rare gastrointestinal tumour traditionally treated with concurrent chemotherapy and radiation. Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, has demonstrated significant efficacy when combined with radiation in squamous cell carcinoma of the head and neck (SccH&N). We wanted to assess EGFR and Kirsten-ras (K-ras) status in SCAC to see whether it compares with SccH&N.Methods:Over 90 SCAC paraffin-embedded biopsies were mounted onto a tissue microarray and were assessed for EGFR expression by immunohistochemistry. These samples were also assessed for the most frequently mutated K-ras and EGFR exons by high-resolution melting analysis.Results:The EGFR was present in over 90% of samples tested. The K-ras and EGFR mutations were absent in all samples tested, although a synonymous single-nucleotide polymorphism was found in 3 out of 89 samples tested for EGFR exon 19.Conclusion:The low rate of K-ras and EGFR mutations, coupled with the high surface expression of EGFR, suggests similarity in the EGFR signalling pathway between SCAC and SccH&N, and thus a potential role for EGFR inhibitors in SCAC. To our knowledge this is the largest cohort of invasive SCAC samples investigated for EGFR and K-ras mutations reported to date.

Original languageEnglish (US)
Pages (from-to)1864-1868
Number of pages5
JournalBritish Journal of Cancer
Volume107
Issue number11
DOIs
StatePublished - Nov 20 2012
Externally publishedYes

Fingerprint

ras Genes
Epidermal Growth Factor Receptor
Squamous Cell Carcinoma
Radiation
Mutation
Exons
Radio
Paraffin
Freezing
Single Nucleotide Polymorphism
Neoplasms
Immunohistochemistry

Keywords

  • anal carcinoma
  • EGFR
  • high-resolution melting analysis
  • immunohistochemistry
  • K-ras

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

EGFR and K-ras gene mutation status in squamous cell anal carcinoma : A role for concurrent radiation and EGFR inhibitors. / Paliga, A.; Onerheim, R.; Gologan, A.; Chong, G.; Spatz, A.; Niazi, T.; Garant, A.; MacHeto, D.; Alcindor, T.; Vuong, T.

In: British Journal of Cancer, Vol. 107, No. 11, 20.11.2012, p. 1864-1868.

Research output: Contribution to journalArticle

Paliga, A, Onerheim, R, Gologan, A, Chong, G, Spatz, A, Niazi, T, Garant, A, MacHeto, D, Alcindor, T & Vuong, T 2012, 'EGFR and K-ras gene mutation status in squamous cell anal carcinoma: A role for concurrent radiation and EGFR inhibitors', British Journal of Cancer, vol. 107, no. 11, pp. 1864-1868. https://doi.org/10.1038/bjc.2012.479
Paliga, A. ; Onerheim, R. ; Gologan, A. ; Chong, G. ; Spatz, A. ; Niazi, T. ; Garant, A. ; MacHeto, D. ; Alcindor, T. ; Vuong, T. / EGFR and K-ras gene mutation status in squamous cell anal carcinoma : A role for concurrent radiation and EGFR inhibitors. In: British Journal of Cancer. 2012 ; Vol. 107, No. 11. pp. 1864-1868.
@article{788a5bde86c646bea1fdf2e18390a7a6,
title = "EGFR and K-ras gene mutation status in squamous cell anal carcinoma: A role for concurrent radiation and EGFR inhibitors",
abstract = "Background:There is a growing appreciation for radio-sensitiser use in multi-modal cancer treatment models. Squamous cell anal carcinoma (SCAC) is a rare gastrointestinal tumour traditionally treated with concurrent chemotherapy and radiation. Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, has demonstrated significant efficacy when combined with radiation in squamous cell carcinoma of the head and neck (SccH&N). We wanted to assess EGFR and Kirsten-ras (K-ras) status in SCAC to see whether it compares with SccH&N.Methods:Over 90 SCAC paraffin-embedded biopsies were mounted onto a tissue microarray and were assessed for EGFR expression by immunohistochemistry. These samples were also assessed for the most frequently mutated K-ras and EGFR exons by high-resolution melting analysis.Results:The EGFR was present in over 90{\%} of samples tested. The K-ras and EGFR mutations were absent in all samples tested, although a synonymous single-nucleotide polymorphism was found in 3 out of 89 samples tested for EGFR exon 19.Conclusion:The low rate of K-ras and EGFR mutations, coupled with the high surface expression of EGFR, suggests similarity in the EGFR signalling pathway between SCAC and SccH&N, and thus a potential role for EGFR inhibitors in SCAC. To our knowledge this is the largest cohort of invasive SCAC samples investigated for EGFR and K-ras mutations reported to date.",
keywords = "anal carcinoma, EGFR, high-resolution melting analysis, immunohistochemistry, K-ras",
author = "A. Paliga and R. Onerheim and A. Gologan and G. Chong and A. Spatz and T. Niazi and A. Garant and D. MacHeto and T. Alcindor and T. Vuong",
year = "2012",
month = "11",
day = "20",
doi = "10.1038/bjc.2012.479",
language = "English (US)",
volume = "107",
pages = "1864--1868",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "11",

}

TY - JOUR

T1 - EGFR and K-ras gene mutation status in squamous cell anal carcinoma

T2 - A role for concurrent radiation and EGFR inhibitors

AU - Paliga, A.

AU - Onerheim, R.

AU - Gologan, A.

AU - Chong, G.

AU - Spatz, A.

AU - Niazi, T.

AU - Garant, A.

AU - MacHeto, D.

AU - Alcindor, T.

AU - Vuong, T.

PY - 2012/11/20

Y1 - 2012/11/20

N2 - Background:There is a growing appreciation for radio-sensitiser use in multi-modal cancer treatment models. Squamous cell anal carcinoma (SCAC) is a rare gastrointestinal tumour traditionally treated with concurrent chemotherapy and radiation. Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, has demonstrated significant efficacy when combined with radiation in squamous cell carcinoma of the head and neck (SccH&N). We wanted to assess EGFR and Kirsten-ras (K-ras) status in SCAC to see whether it compares with SccH&N.Methods:Over 90 SCAC paraffin-embedded biopsies were mounted onto a tissue microarray and were assessed for EGFR expression by immunohistochemistry. These samples were also assessed for the most frequently mutated K-ras and EGFR exons by high-resolution melting analysis.Results:The EGFR was present in over 90% of samples tested. The K-ras and EGFR mutations were absent in all samples tested, although a synonymous single-nucleotide polymorphism was found in 3 out of 89 samples tested for EGFR exon 19.Conclusion:The low rate of K-ras and EGFR mutations, coupled with the high surface expression of EGFR, suggests similarity in the EGFR signalling pathway between SCAC and SccH&N, and thus a potential role for EGFR inhibitors in SCAC. To our knowledge this is the largest cohort of invasive SCAC samples investigated for EGFR and K-ras mutations reported to date.

AB - Background:There is a growing appreciation for radio-sensitiser use in multi-modal cancer treatment models. Squamous cell anal carcinoma (SCAC) is a rare gastrointestinal tumour traditionally treated with concurrent chemotherapy and radiation. Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, has demonstrated significant efficacy when combined with radiation in squamous cell carcinoma of the head and neck (SccH&N). We wanted to assess EGFR and Kirsten-ras (K-ras) status in SCAC to see whether it compares with SccH&N.Methods:Over 90 SCAC paraffin-embedded biopsies were mounted onto a tissue microarray and were assessed for EGFR expression by immunohistochemistry. These samples were also assessed for the most frequently mutated K-ras and EGFR exons by high-resolution melting analysis.Results:The EGFR was present in over 90% of samples tested. The K-ras and EGFR mutations were absent in all samples tested, although a synonymous single-nucleotide polymorphism was found in 3 out of 89 samples tested for EGFR exon 19.Conclusion:The low rate of K-ras and EGFR mutations, coupled with the high surface expression of EGFR, suggests similarity in the EGFR signalling pathway between SCAC and SccH&N, and thus a potential role for EGFR inhibitors in SCAC. To our knowledge this is the largest cohort of invasive SCAC samples investigated for EGFR and K-ras mutations reported to date.

KW - anal carcinoma

KW - EGFR

KW - high-resolution melting analysis

KW - immunohistochemistry

KW - K-ras

UR - http://www.scopus.com/inward/record.url?scp=84870057448&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870057448&partnerID=8YFLogxK

U2 - 10.1038/bjc.2012.479

DO - 10.1038/bjc.2012.479

M3 - Article

C2 - 23093229

AN - SCOPUS:84870057448

VL - 107

SP - 1864

EP - 1868

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 11

ER -