Classification of HER2/neu Status in Gastric Cancer Using a Breast-Cancer Derived Proteome Classifier

被引:58
作者
Balluff, Benjamin [2 ,3 ]
Elsner, Mareike [3 ]
Kowarsch, Andreas [4 ]
Rauser, Sandra [3 ]
Meding, Stephan [3 ]
Schuhmacher, Christoph
Feith, Marcus
Herrmann, Ken [5 ]
Rocken, Christoph [7 ]
Schmid, Roland M. [2 ]
Hofler, Heinz [3 ,6 ]
Walch, Axel [3 ]
Ebert, Matthias P. [1 ,2 ]
机构
[1] Heidelberg Univ, Univ Med Mannheim, Dept Med 2, D-68167 Mannheim, Germany
[2] Tech Univ Munich, Klinikum Rechts Isar, Dept Med 2, D-8000 Munich, Germany
[3] Helmholtz Zentrum Munchen, Inst Pathol, German Res Ctr Environm Hlth, Neuherberg, Germany
[4] Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, German Res Ctr Environm Hlth, Neuherberg, Germany
[5] Tech Univ Munich, Klinikum Rechts Isar, Dept Nucl Med, D-8000 Munich, Germany
[6] Tech Univ Munich, Klinikum Rechts Isar, Inst Pathol, D-8000 Munich, Germany
[7] Univ Kiel, Inst Pathol, D-2300 Kiel, Germany
关键词
HER2; testing; gastric cancer; MALDI Imaging; molecular classification; tumor biology; IMAGING MASS-SPECTROMETRY; MONOCLONAL-ANTIBODY; TRASTUZUMAB; GROWTH; AMPLIFICATION; EXPRESSION; PREDICTION; PEPTIDES; HER-2;
D O I
10.1021/pr100573s
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
HER2-testing in breast and gastric cancers is mandatory for the treatment with trastuzumab We hypothesized that imaging mass spectrometry (IMS) of breast cancers may be useful for generating a classifier that may determine HER2-status in other cancer entities irrespective of primary tumor site A total of 107 breast (n = 48) and gastric (n = 59) cryo tissue samples was analyzed by IMS (HER2 was present in 29 cases) The obtained proteomic profiles were used to create HER2 prediction models using different classification algorithms A breast cancer proteome derived classifier, with HER2 present in 15 cases, correctly predicted HER2-status in gastric cancers with a sensitivity of 65% and a specificity of 92% To create a universal classifier for HER2-status, breast and nonbreast cancer samples were combined, which increased sensitivity to 78% and specificity was 88% Our proof of principle study provides evidence that HER2-status can be identified on a proteomic level across different cancer types suggesting that HER2 overexpression may constitute a unique molecular event independent of the tumor site Furthermore these results indicate that IMS may be useful for the determination of potential drugable targets as it offers a quicker cheaper and more objective analysis than the standard HER2 testing procedures immunohistochemistry and fluorescence in situ hybridization
引用
收藏
页码:6317 / 6322
页数:6
相关论文
共 38 条
[1]  
Adam BL, 2002, CANCER RES, V62, P3609
[2]   Identification of diagnostic markers for tuberculosis by proteomic fingerprinting of serum [J].
Agranoff, Dan ;
Fernandez-Reyes, Delmiro ;
Papadopoulos, Marios C. ;
Rojas, Sergio A. ;
Herbster, Mark ;
Loosemore, Alison ;
Tarelli, Edward ;
Sheldon, Jo ;
Schwenk, Achim ;
Pollak, Richard ;
Rayner, Charlotte F. J. ;
Krishna, Sarjeev .
LANCET, 2006, 368 (9540) :1012-1021
[3]  
Bang YJ, 2010, LANCET, V376, P1302
[4]   The clinical evaluation of HER-2 status: which test to use? [J].
Bartlett, J ;
Mallon, E ;
Cooke, T .
JOURNAL OF PATHOLOGY, 2003, 199 (04) :411-417
[5]   Random forests [J].
Breiman, L .
MACHINE LEARNING, 2001, 45 (01) :5-32
[6]   Molecular imaging of biological samples: Localization of peptides and proteins using MALDI-TOF MS [J].
Caprioli, RM ;
Farmer, TB ;
Gile, J .
ANALYTICAL CHEMISTRY, 1997, 69 (23) :4751-4760
[7]   Comparison of different commercial kits for HER2 testing in breast cancer: looking for the accurate cutoff for amplification [J].
Cayre, Anne ;
Mishellany, Florence ;
Lagarde, Nicole ;
Penault-Llorca, Fredirique .
BREAST CANCER RESEARCH, 2007, 9 (05) :R64
[8]   Imaging Mass Spectrometry of a Specific Fragment of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase Kinase 2 Discriminates Cancer from Uninvolved Prostate Tissue [J].
Cazares, Lisa H. ;
Troyer, Dean ;
Mendrinos, Sawas ;
Lance, Raymond A. ;
Nyalwidhe, Julius O. ;
Beydoun, Hind A. ;
Clements, Mary Ann ;
Drake, Richard R. ;
Semmes, O. John .
CLINICAL CANCER RESEARCH, 2009, 15 (17) :5541-5551
[9]   Proteomics in diagnostic pathology - Profiling and imaging proteins directly in tissue sections [J].
Chaurand, P ;
Sanders, ME ;
Jensen, RA ;
Caprioli, RM .
AMERICAN JOURNAL OF PATHOLOGY, 2004, 165 (04) :1057-1068
[10]   MALDI imaging mass spectrometry: molecular snapshots of biochemical systems [J].
Cornett, Dale S. ;
Reyzer, Michelle L. ;
Chaurand, Pierre ;
Caprioli, Richard M. .
NATURE METHODS, 2007, 4 (10) :828-833