| 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. |
| Authors | Daphne Gschwantler-Kaulich, Gernot Hudelist, Wolfgang J Koestler, Klaus Czerwenka, Ruth Mueller, Samir Helmy, Ernst Ruecklinger, Ernst Kubista, Christian F Singer
(Affiliation: Division of Special Gynecology, Department of OB/GYN, Vienna Medical University, Waehringer Guertel 18-20, A-1090 Vienna, Austria.)
|
| Journal | Oncology reports
(Oncol Rep)
Vol. 14
Issue 2
Pg. 305-11
(Aug 2005)
ISSN: 1021-335X Greece |
| PMID | 16012707
(Publication Type: Comparative Study, Journal Article)
|
| Chemical References |
- Receptor, Epidermal Growth Factor
- Receptor, erbB-2
|
| Topics |
- Adult
- Aged
- Aged, 80 and over
- Breast Neoplasms
(blood, metabolism, pathology)
- Female
- Humans
- Immunohistochemistry
- Middle Aged
- Neoplasm Metastasis
- Phosphorylation
- Prognosis
- Receptor, Epidermal Growth Factor
(blood, metabolism)
- Receptor, erbB-2
(metabolism)
|
