Dissecting the EGFR-PI3K-AKT pathway in oral cancer highlights the role of the EGFR variant III and its clinical relevance

Kwang Yu Chang, Shan Yin Tsai, Shang Hung Chen, Hsiao Hui Tsou, Chia Jui Yen, Ko Jiunn Liu, Hsun Lang Fang, Hung Chang Wu, Bin Fay Chuang, Shao Wen Chou, Careen K. Tang, Shyun Yeu Liu, Pei Jung Lu, Ching Yu Yen, Jang Yang Chang

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Abstract

Background: Dysregulated epidermal growth factor receptor (EGFR)-phosphoinositide-3-kinase (PI3K)-AKT signaling is considered pivotal for oral cancer, and the pathway is a potential candidate for therapeutic targeting. Results: A total of 108 archival samples which were from surgically resected oral cancer were examined. Immunohistochemical staining showed the protein expression of membranous wild-type EGFR and cytoplasmic phosphorylated AKT was detected in 63.9% and 86.9% of the specimens, respectively. In 49.1% of the samples, no phosphatase and tensin homolog (PTEN) expression was detected. With regard to the EGFR variant III (EGFRvIII), 75.0% of the samples showed positive expression for moderate to severe staining, 31.5% of which had high expression levels. Real-time polymerase chain reaction assays for gene copy number assessment of PIK3CA revealed that 24.8% of the samples had alterations, and of EGFR showed that 49.0% had amplification. Direct sequencing of PIK3CA gene showed 2.3% of the samples had a hotspot point mutation. Statistical assessment showed the expression of the EGFRvIII correlated with the T classification and TNM stage. The Kaplan-Meier analyses for patient survival showed that the individual status of phosphorylated AKT and EGFRvIII led to significant differences in survival outcome. The multivariate analysis indicated that phosphorylated AKT, EGFRvIII expression and disease stage were patient survival determinants. Conclusions: Aberrations in the EGFR-PI3K-AKT pathway were frequently found in oral cancers. EGFRvIII and phosphorylated AKT were predictors for the patient survival and clinical outcome.

Original languageEnglish
Article number43
JournalJournal of Biomedical Science
Volume20
Issue number1
DOIs
Publication statusPublished - 2013

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1-Phosphatidylinositol 4-Kinase
Mouth Neoplasms
Phosphatidylinositols
Epidermal Growth Factor Receptor
Phosphotransferases
Survival
Genes
Staining and Labeling
Gene Dosage
Neoplasm Staging
Polymerase chain reaction
Kaplan-Meier Estimate
Aberrations
Phosphoric Monoester Hydrolases
Point Mutation
Amplification
Real-Time Polymerase Chain Reaction
Assays
Multivariate Analysis
Proteins

Keywords

  • AKT
  • EGFR
  • EGFRvIII
  • Oral cancer
  • PI3K
  • PTEN

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)
  • Medicine(all)

Cite this

Dissecting the EGFR-PI3K-AKT pathway in oral cancer highlights the role of the EGFR variant III and its clinical relevance. / Chang, Kwang Yu; Tsai, Shan Yin; Chen, Shang Hung; Tsou, Hsiao Hui; Yen, Chia Jui; Liu, Ko Jiunn; Fang, Hsun Lang; Wu, Hung Chang; Chuang, Bin Fay; Chou, Shao Wen; Tang, Careen K.; Liu, Shyun Yeu; Lu, Pei Jung; Yen, Ching Yu; Chang, Jang Yang.

In: Journal of Biomedical Science, Vol. 20, No. 1, 43, 2013.

Research output: Contribution to journalArticle

Chang, KY, Tsai, SY, Chen, SH, Tsou, HH, Yen, CJ, Liu, KJ, Fang, HL, Wu, HC, Chuang, BF, Chou, SW, Tang, CK, Liu, SY, Lu, PJ, Yen, CY & Chang, JY 2013, 'Dissecting the EGFR-PI3K-AKT pathway in oral cancer highlights the role of the EGFR variant III and its clinical relevance', Journal of Biomedical Science, vol. 20, no. 1, 43. https://doi.org/10.1186/1423-0127-20-43
Chang, Kwang Yu ; Tsai, Shan Yin ; Chen, Shang Hung ; Tsou, Hsiao Hui ; Yen, Chia Jui ; Liu, Ko Jiunn ; Fang, Hsun Lang ; Wu, Hung Chang ; Chuang, Bin Fay ; Chou, Shao Wen ; Tang, Careen K. ; Liu, Shyun Yeu ; Lu, Pei Jung ; Yen, Ching Yu ; Chang, Jang Yang. / Dissecting the EGFR-PI3K-AKT pathway in oral cancer highlights the role of the EGFR variant III and its clinical relevance. In: Journal of Biomedical Science. 2013 ; Vol. 20, No. 1.
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abstract = "Background: Dysregulated epidermal growth factor receptor (EGFR)-phosphoinositide-3-kinase (PI3K)-AKT signaling is considered pivotal for oral cancer, and the pathway is a potential candidate for therapeutic targeting. Results: A total of 108 archival samples which were from surgically resected oral cancer were examined. Immunohistochemical staining showed the protein expression of membranous wild-type EGFR and cytoplasmic phosphorylated AKT was detected in 63.9{\%} and 86.9{\%} of the specimens, respectively. In 49.1{\%} of the samples, no phosphatase and tensin homolog (PTEN) expression was detected. With regard to the EGFR variant III (EGFRvIII), 75.0{\%} of the samples showed positive expression for moderate to severe staining, 31.5{\%} of which had high expression levels. Real-time polymerase chain reaction assays for gene copy number assessment of PIK3CA revealed that 24.8{\%} of the samples had alterations, and of EGFR showed that 49.0{\%} had amplification. Direct sequencing of PIK3CA gene showed 2.3{\%} of the samples had a hotspot point mutation. Statistical assessment showed the expression of the EGFRvIII correlated with the T classification and TNM stage. The Kaplan-Meier analyses for patient survival showed that the individual status of phosphorylated AKT and EGFRvIII led to significant differences in survival outcome. The multivariate analysis indicated that phosphorylated AKT, EGFRvIII expression and disease stage were patient survival determinants. Conclusions: Aberrations in the EGFR-PI3K-AKT pathway were frequently found in oral cancers. EGFRvIII and phosphorylated AKT were predictors for the patient survival and clinical outcome.",
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T1 - Dissecting the EGFR-PI3K-AKT pathway in oral cancer highlights the role of the EGFR variant III and its clinical relevance

AU - Chang, Kwang Yu

AU - Tsai, Shan Yin

AU - Chen, Shang Hung

AU - Tsou, Hsiao Hui

AU - Yen, Chia Jui

AU - Liu, Ko Jiunn

AU - Fang, Hsun Lang

AU - Wu, Hung Chang

AU - Chuang, Bin Fay

AU - Chou, Shao Wen

AU - Tang, Careen K.

AU - Liu, Shyun Yeu

AU - Lu, Pei Jung

AU - Yen, Ching Yu

AU - Chang, Jang Yang

PY - 2013

Y1 - 2013

N2 - Background: Dysregulated epidermal growth factor receptor (EGFR)-phosphoinositide-3-kinase (PI3K)-AKT signaling is considered pivotal for oral cancer, and the pathway is a potential candidate for therapeutic targeting. Results: A total of 108 archival samples which were from surgically resected oral cancer were examined. Immunohistochemical staining showed the protein expression of membranous wild-type EGFR and cytoplasmic phosphorylated AKT was detected in 63.9% and 86.9% of the specimens, respectively. In 49.1% of the samples, no phosphatase and tensin homolog (PTEN) expression was detected. With regard to the EGFR variant III (EGFRvIII), 75.0% of the samples showed positive expression for moderate to severe staining, 31.5% of which had high expression levels. Real-time polymerase chain reaction assays for gene copy number assessment of PIK3CA revealed that 24.8% of the samples had alterations, and of EGFR showed that 49.0% had amplification. Direct sequencing of PIK3CA gene showed 2.3% of the samples had a hotspot point mutation. Statistical assessment showed the expression of the EGFRvIII correlated with the T classification and TNM stage. The Kaplan-Meier analyses for patient survival showed that the individual status of phosphorylated AKT and EGFRvIII led to significant differences in survival outcome. The multivariate analysis indicated that phosphorylated AKT, EGFRvIII expression and disease stage were patient survival determinants. Conclusions: Aberrations in the EGFR-PI3K-AKT pathway were frequently found in oral cancers. EGFRvIII and phosphorylated AKT were predictors for the patient survival and clinical outcome.

AB - Background: Dysregulated epidermal growth factor receptor (EGFR)-phosphoinositide-3-kinase (PI3K)-AKT signaling is considered pivotal for oral cancer, and the pathway is a potential candidate for therapeutic targeting. Results: A total of 108 archival samples which were from surgically resected oral cancer were examined. Immunohistochemical staining showed the protein expression of membranous wild-type EGFR and cytoplasmic phosphorylated AKT was detected in 63.9% and 86.9% of the specimens, respectively. In 49.1% of the samples, no phosphatase and tensin homolog (PTEN) expression was detected. With regard to the EGFR variant III (EGFRvIII), 75.0% of the samples showed positive expression for moderate to severe staining, 31.5% of which had high expression levels. Real-time polymerase chain reaction assays for gene copy number assessment of PIK3CA revealed that 24.8% of the samples had alterations, and of EGFR showed that 49.0% had amplification. Direct sequencing of PIK3CA gene showed 2.3% of the samples had a hotspot point mutation. Statistical assessment showed the expression of the EGFRvIII correlated with the T classification and TNM stage. The Kaplan-Meier analyses for patient survival showed that the individual status of phosphorylated AKT and EGFRvIII led to significant differences in survival outcome. The multivariate analysis indicated that phosphorylated AKT, EGFRvIII expression and disease stage were patient survival determinants. Conclusions: Aberrations in the EGFR-PI3K-AKT pathway were frequently found in oral cancers. EGFRvIII and phosphorylated AKT were predictors for the patient survival and clinical outcome.

KW - AKT

KW - EGFR

KW - EGFRvIII

KW - Oral cancer

KW - PI3K

KW - PTEN

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U2 - 10.1186/1423-0127-20-43

DO - 10.1186/1423-0127-20-43

M3 - Article

VL - 20

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

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