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

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• 作者：Kwang-Yu Chang (1) (2) (4)
  Shan-Yin Tsai (5)
  Shang-Hung Chen (2) (6)
  Hsiao-Hui Tsou (3)
  Chia-Jui Yen (4)
  Ko-Jiunn Liu (2)
  Hsun-Lang Fang (7)
  Hung-Chang Wu (8)
  Bin-Fay Chuang (2)
  Shao-Wen Chou (2)
  Careen K Tang (10)
  Shyun-Yeu Liu (11) (9)
  Pei-Jung Lu (1)
  Ching-Yu Yen (12) (9)
  Jang-Yang Chang (2) (4)
  
• 关键词：AKT ; EGFR ; EGFRvIII ; Oral cancer ; PI3K ; PTEN
• 刊名：Journal of Biomedical Science
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：20
• 期：1
• 全文大小：953 KB
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• 作者单位：Kwang-Yu Chang (1) (2) (4)
  Shan-Yin Tsai (5)
  Shang-Hung Chen (2) (6)
  Hsiao-Hui Tsou (3)
  Chia-Jui Yen (4)
  Ko-Jiunn Liu (2)
  Hsun-Lang Fang (7)
  Hung-Chang Wu (8)
  Bin-Fay Chuang (2)
  Shao-Wen Chou (2)
  Careen K Tang (10)
  Shyun-Yeu Liu (11) (9)
  Pei-Jung Lu (1)
  Ching-Yu Yen (12) (9)
  Jang-Yang Chang (2) (4)
  
  1. Institute of Clinical Medicine College of Medicine, National Cheng Kung University, 7th Floor, No.35 Xiaodong Rd, Tainan City, 701, Taiwan
  2. National Institute of Cancer Research National Health Research Institutes, 2nd Floor No.367, Shengli Rd, Tainan City, 70456, Taiwan
  4. Division of Hematology/Oncology Department of Internal Medicine, National Cheng Kung University Hospital, No.138 Shengli Rd, Tainan, 704, Taiwan
  5. Department of Pathology, Kaohsiung Medical University Hospital, No.100 , Tzyou 1st Rd, Kaohsiung, 807, Taiwan
  6. Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Liouying, No. 201, Taikang Village, Liuying Dist, Tainan City, 73657, Taiwan
  3. Institute of Population Health Sciences National Health Research Institutes, No.35 Keyan Road, Zhunan, Miaoli County, 35053, Taiwan
  7. Department of Cosmetology and Health Care, Min-Hwei College of Health Care Management, No.1116, Sec. 2, Zhongshan E. Rd., Liuying Dist, Tainan, 73658, Taiwan
  8. Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, No.901, Zhonghua Rd, Tainan City, Yongkang Dist, 710, Taiwan
  10. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3800 Reservoir Rd, Washington, DC, 20057, USA
  11. Department of Dentistry, National Defense Medical Center, No.161, Sec. 6, Minquan E. Rd, Taipei City, Neihu District 114, Taiwan
  9. Oral and Maxillofacial Surgery Section, Chi-Mei Medical Center, No.901, Zhonghua Rd, Tainan City, Yongkang Dist, 710, Taiwan
  12. Department of Dentistry, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei City, 110, Taiwan
  
• ISSN：1423-0127

文摘

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.