Classification of HER2/neu status in gastric cancer using a breast-cancer derived proteome classifier.
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.
Department of Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Benjamin
B
Balluff
Mareike
M
Elsner
Andreas
A
Kowarsch
Sandra
S
Rauser
Stephan
S
Meding
Christoph
C
Schuhmacher
Marcus
M
Feith
Ken
K
Herrmann
Christoph
C
Röcken
Roland M
RM
Schmid
Heinz
H
Höfler
Axel
A
Walch
Matthias P
MP
Ebert
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*
D018719:Erb-b2 Receptor Tyrosine Kinases