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Updated: Jun 18, 2026
Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
Expression of epidermal growth factor receptor (EGFR) and activated EGFR predict poor response to (chemo)radiation
Maartje G Noordhuis1, Jasper J H Eijsink, Klaske A Ten Hoor
1Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Purpose:
Activation of the epidermal growth factor receptor (EGFR) signaling pathway has been reported to induce resistance to (chemo)radiation in cancers, such as head and neck cancer, whereas EGFR-targeted agents in combination with (chemo)radiation seem to improve treatment efficacy. The aim of this study was to determine the relation between proteins involved in the EGFR pathway and response to (chemo)radiation and survival in a large, well-documented series of cervical cancer patients.
Experimental Design:
Pretreatment tissue samples of 375 consecutive International Federation of Gynecologists and Obstetricians stage Ib to IVa cervical cancer patients treated with (chemo)radiation between January 1980 and December 2006 were collected. Clinicopathologic and follow-up data were prospectively obtained during standard treatment and follow-up. Protein expression of EGFR, phosphorylated EGFR (pEGFR), PTEN, phosphorylated AKT, and phosphorylated extracellular signal-regulated kinase (pERK) was assessed by immunohistochemistry on tissue microarrays.
Results:
EGFR staining was present in 35.3%, pEGFR in 19.7%, PTEN in 34.1%, phosphorylated AKT in 4.1%, and pERK in 29.2% of tumors. pEGFR staining was related to PTEN (P = 0.001) and pERK staining (P = 0.004). EGFR staining was inversely related to PTEN (P = 0.011). In multivariate analysis, membranous staining of EGFR [hazard ratio (HR), 1.84; 95% confidence interval (95% CI), 1.20-2.82; P = 0.005] and cytoplasmic staining of pEGFR (HR, 1.71; 95% CI, 1.11-2.66; P = 0.016) were independent predictors of poor response to (chemo)radiation. Membranous EGFR staining also was an independent prognostic factor for poor disease-specific survival (HR, 1.54; 95% CI, 1.09-2.17; P = 0.014).
Conclusions:
EGFR and pEGFR immunostainings are frequently observed and independently associated with poor response to therapy and disease-specific survival in cervical cancer patients primarily treated by (chemo)radiation. Our data present the EGFR pathway as a promising therapeutic target in already ongoing clinical trials.
Insights
High levels of epidermal growth factor receptor (EGFR) and phosphorylated EGFR (pEGFR) in cervical tumors predict poor response to chemoradiation and reduced survival. Targeting the EGFR pathway may improve treatment outcomes for cervical cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Epidermal growth factor receptor (EGFR) signaling pathway activation is linked to chemoresistance in various cancers.
- EGFR-targeted therapies combined with chemoradiation show potential for improving cancer treatment efficacy.
Purpose of the Study:
- To investigate the association between proteins in the EGFR pathway and treatment response.
- To determine the prognostic value of EGFR pathway proteins for survival in cervical cancer patients treated with chemoradiation.
Main Methods:
- Immunohistochemistry was used to assess protein expression (EGFR, pEGFR, PTEN, pAKT, pERK) in pretreatment tumor samples from 375 cervical cancer patients.
- Clinicopathologic and follow-up data were prospectively collected for patients treated between 1980 and 2006.
Main Results:
- EGFR and pEGFR were frequently expressed in cervical tumors (35.3% and 19.7%, respectively).
- Membranous EGFR and cytoplasmic pEGFR staining independently predicted a poor response to chemoradiation.
- Membranous EGFR staining was also an independent prognostic factor for reduced disease-specific survival.
Conclusions:
- EGFR and pEGFR expression are common in cervical cancer and are associated with unfavorable treatment response and survival outcomes.
- The EGFR pathway represents a potential therapeutic target for cervical cancer, with ongoing clinical trials investigating its role.
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