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Balluff, B. ; Elsner, M. ; Kowarsch, A. ; Rauser, S. ; Meding, S. ; Schuhmacher, C.* ; Feith, M.* ; Herrmann, K.* ; Röcken, C.* ; Schmid, R.M.* ; Höfler, H. ; Walch, A.K. ; Ebert, M.P.*

Classification of HER2/neu status in gastric cancer using a breast-cancer derived proteome classifier.

J. Proteome Res. 9, 6317-6322 (2010)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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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.

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