Expression of MET and SOX2 genes in non-small cell lung carcinoma with EGFR mutation

被引:18
作者
Cai, Yi-Ran [1 ]
Zhang, Hai-Qing [1 ]
Qu, Yang [1 ]
Mu, Jing [1 ]
Zhao, Dan [1 ]
Zhou, Li-Juan [1 ]
Yan, Hong [1 ]
Ye, Jian-Wei [2 ]
Liu, Yan [2 ]
机构
[1] Capital Med Univ, Beijing Chest Hosp, Dept Pathol, Beijing 101149, Peoples R China
[2] Wu Jieping Med Fdn, Div Mol Med, Beijing 100144, Peoples R China
基金
北京市自然科学基金;
关键词
non-small cell lung carcinoma; MET gene; SOX2; gene; EGFR mutation; immunohistochemistry; GROWTH-FACTOR-RECEPTOR; C-MET; ACQUIRED-RESISTANCE; TYROSINE KINASE; CANCER CELLS; STEM-CELLS; GEFITINIB; AMPLIFICATION; ADENOCARCINOMA; ONCOGENE;
D O I
10.3892/or.2011.1349
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer-related deaths. Aberrance of the two oncogenes MET and SOX2 are frequently encountered in NSCLC. Exons 18 through 21 of the EGFR gene were screened and MET and SOX2 immunostaining was conducted to analyze the immunohistological staining of MET and SOX2 and the EGFR mutation status. One hundred and fifty tissue samples were examined including 57 squamous cell carcinomas (SCCs), 80 adenocarcinomas (ADCs), 9 adenosquamous carcinomas (ADSCs) and 4 large cell carcinomas (LCCs). The 32 NSCLCs harboring an EGFR mutation included 28 ADCs, 3 SCCs and 1 ADSC. A higher level of SOX2 expression appeared in NSCLCs without the EGFR mutation compared to those with EGFR mutation (chi(2)=9.02, P=0.0027). Of the 28 ADCs, 24 (85.7%) with an EGFR mutation showed low level of SOX2 expression. ADCs with deletion in exon 19 overexpressed MET and showed low levels of SOX2. SOX2 expression was inversely correlated to the expression of MET in NSCLC and mainly present in non-mutated NSCLC (r=-0.42, P<0.0001). There was a tendency for SOX2 to be expressed in SCCs and particularly in the part of SCC among ADSCs, whereas MET was mainly expressed in the part of ADC among ADSCs and ADCs. High level of MET and SOX2 expression were respectively demonstrated in ADCs and SCCs; MET activation was accompanied with exon 19 deletion in ADCs. EGFR and MET coordinate to drive tumorigenesis. Detection of the activation of MET and EGFR may be used for targeted drug therapy.
引用
收藏
页码:877 / 885
页数:9
相关论文
共 49 条
  • [1] [Anonymous], 2004, Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs
  • [2] SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas
    Bass, Adam J.
    Watanabe, Hideo
    Mermel, Craig H.
    Yu, Soyoung
    Perner, Sven
    Verhaak, Roel G.
    Kim, So Young
    Wardwell, Leslie
    Tamayo, Pablo
    Gat-Viks, Irit
    Ramos, Alex H.
    Woo, Michele S.
    Weir, Barbara A.
    Getz, Gad
    Beroukhim, Rameen
    O'Kelly, Michael
    Dutt, Amit
    Rozenblatt-Rosen, Orit
    Dziunycz, Piotr
    Komisarof, Justin
    Chirieac, Lucian R.
    LaFargue, Christopher J.
    Scheble, Veit
    Wilbertz, Theresia
    Ma, Changqing
    Rao, Shilpa
    Nakagawa, Hiroshi
    Stairs, Douglas B.
    Lin, Lin
    Giordano, Thomas J.
    Wagner, Patrick
    Minna, John D.
    Gazdar, Adi F.
    Zhu, Chang Qi
    Brose, Marcia S.
    Cecconello, Ivan
    Ribeiro, Ulysses, Jr.
    Marie, Suely K.
    Dahl, Olav
    Shivdasani, Ramesh A.
    Tsao, Ming-Sound
    Rubin, Mark A.
    Wong, Kwok K.
    Regev, Aviv
    Hahn, William C.
    Beer, David G.
    Rustgi, Anil K.
    Meyerson, Matthew
    [J]. NATURE GENETICS, 2009, 41 (11) : 1238 - U105
  • [3] Are adenosquamous lung carcinomas a simple mix of adenocarcinomas and squamous cell carcinomas, or more complex at the molecular level?
    Bastide, Kristell
    Ugolin, Nicolas
    Levalois, Celine
    Bernaudin, Jean-Francois
    Chevillard, Sylvie
    [J]. LUNG CANCER, 2010, 68 (01) : 1 - 9
  • [4] MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib
    Bean, James
    Brennan, Cameron
    Shih, Jin-Yuan
    Riely, Gregory
    Viale, Agnes
    Wang, Lu
    Chitale, Dhananjay
    Motoi, Noriko
    Szoke, Janos
    Broderick, Stephen
    Balak, Marissa
    Chang, Wen-Cheng
    Yu, Chong-Jen
    Gazdar, Adi
    Pass, Harvey
    Rusch, Valerie
    Gerald, William
    Huang, Shiu-Feng
    Yang, Pan-Chyr
    Miller, Vincent
    Ladany, Marc
    Yang, Chih-Hsin
    Pao, William
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (52) : 20932 - 20937
  • [5] Allelic imbalance at loci containing FGFR, FGF, c-Met and HGF candidate genes in non-small cell lung cancer sub-types, implication for progression
    Beau-Faller, M
    Gaub, MP
    Schneider, A
    Guérin, E
    Meyer, N
    Ducrocq, X
    Massard, G
    Gasser, B
    Kessler, R
    Weitzenblum, E
    Wihlm, JM
    Quoix, E
    Oudet, P
    [J]. EUROPEAN JOURNAL OF CANCER, 2003, 39 (17) : 2538 - 2547
  • [6] An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors
    Ben-Porath, Ittai
    Thomson, Matthew W.
    Carey, Vincent J.
    Ge, Ruping
    Bell, George W.
    Regev, Aviv
    Weinberg, Robert A.
    [J]. NATURE GENETICS, 2008, 40 (05) : 499 - 507
  • [7] Biermann Katharina, 2007, Cancer Genomics & Proteomics, V4, P359
  • [8] Met, metastasis, motility and more
    Birchmeier, C
    Birchmeier, W
    Gherardi, E
    Vande Woude, GF
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (12) : 915 - 925
  • [9] Bjorkqvist AM, 1998, GENE CHROMOSOME CANC, V22, P79
  • [10] IDENTIFICATION OF THE HEPATOCYTE GROWTH-FACTOR RECEPTOR AS THE C-MET PROTOONCOGENE PRODUCT
    BOTTARO, DP
    RUBIN, JS
    FALETTO, DL
    CHAN, AML
    KMIECIK, TE
    VANDEWOUDE, GF
    AARONSON, SA
    [J]. SCIENCE, 1991, 251 (4995) : 802 - 804