EGFR activity in HER-2 over-expressing metastatic breast cancer: evidence for simultaneous phosphorylation of Her-2/neu and EGFR

  • Authors:
    • Daphne Gschwantler-Kaulich
    • Gernot Hudelist
    • Wolfgang J. Koestler
    • Klaus Czerwenka
    • Ruth Mueller
    • Samir Helmy
    • Ernst Ruecklinger
    • Ernst Kubista
    • Christian F. Singer
  • View Affiliations

  • Published online on: August 1, 2005     https://doi.org/10.3892/or.14.2.305
  • Pages: 305-311
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Abstract

Her-2/neu overexpression is an important prognostic parameter in breast cancer patients and has become a response predictor for trastuzumab treatment. Nevertheless, while trastuzumab is highly effective in many Her-2/neu overexpressing tumors, some do not respond. The reason for the differential effect is unknown, but it has been hypothesized that the complex interactions between Her-2/neu and other members of the EGFR family are involved in trastuzumab resistance. We have analyzed the protein expression of Her-2/neu, EGFR, and their activated forms, ptyr-1248 Her-2/neu, ptyr-845 EGFR and ptyr-1173 EGFR, in 57 Her-2/neu overexpressing breast tumors and investigated potential correlations between the receptors. By performing immunohistochemistry on paraffin-embedded tissue sections, we found that ptyr-845 EGFR was significantly co-expressed with Her-2/neu and ptyr-1248 Her-2/neu (p=0.043 and p=0.040, respectively), while ptyr-1173 EGFR was only correlated to Her-2/neu expression (p=0.042). Interestingly, EGFR and its activated forms were all significantly inversely correlated with PgR expression (p=0.011, p=0.033 and p=0.032, respectively), and ptyr-845 EGFR was also inversely correlated with ER expression (p=0.008). While we have previously shown that serum levels of the extracellular component of Her-2/neu are associated with tumoral ptyr-1248 Her-2/neu expression, we did not find a similar relationship between serum EGFR and intratumoral total/activated EGFR. We did, however, observe significantly higher levels of serum EGFR in women with 3+ overexpression of HER-2/neu (p=0.047). Taken together, we have demonstrated the activation pattern of EGFR and Her-2/neu in Her-2/neu overexpressing breast cancer. We suggest that EGFR inhibition might enhance the efficacy of trastuzumab by preventing cross-phosphorylation.

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August 2005
Volume 14 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Gschwantler-Kaulich D, Hudelist G, Koestler WJ, Czerwenka K, Mueller R, Helmy S, Ruecklinger E, Kubista E and Singer CF: EGFR activity in HER-2 over-expressing metastatic breast cancer: evidence for simultaneous phosphorylation of Her-2/neu and EGFR. Oncol Rep 14: 305-311, 2005.
APA
Gschwantler-Kaulich, D., Hudelist, G., Koestler, W.J., Czerwenka, K., Mueller, R., Helmy, S. ... Singer, C.F. (2005). EGFR activity in HER-2 over-expressing metastatic breast cancer: evidence for simultaneous phosphorylation of Her-2/neu and EGFR. Oncology Reports, 14, 305-311. https://doi.org/10.3892/or.14.2.305
MLA
Gschwantler-Kaulich, D., Hudelist, G., Koestler, W. J., Czerwenka, K., Mueller, R., Helmy, S., Ruecklinger, E., Kubista, E., Singer, C. F."EGFR activity in HER-2 over-expressing metastatic breast cancer: evidence for simultaneous phosphorylation of Her-2/neu and EGFR". Oncology Reports 14.2 (2005): 305-311.
Chicago
Gschwantler-Kaulich, D., Hudelist, G., Koestler, W. J., Czerwenka, K., Mueller, R., Helmy, S., Ruecklinger, E., Kubista, E., Singer, C. F."EGFR activity in HER-2 over-expressing metastatic breast cancer: evidence for simultaneous phosphorylation of Her-2/neu and EGFR". Oncology Reports 14, no. 2 (2005): 305-311. https://doi.org/10.3892/or.14.2.305