Higher nuclear EGFR expression is a better predictor of survival in rectal cancer patients following neoadjuvant chemoradiotherapy than cytoplasmic EGFR expression

Yang,Ching‑Chieh; Lin,Li‑Ching; Lin,Yu‑Wei; Tian,Yu‑Feng; Lin,Chen‑Yi; Sheu,Ming‑Jen; Li,Chien‑Feng; Tai,Ming‑Hong

doi:10.3892/ol.2018.9756

Higher nuclear EGFR expression is a better predictor of survival in rectal cancer patients following neoadjuvant chemoradiotherapy than cytoplasmic EGFR expression

Authors:
- Ching‑Chieh Yang
- Li‑Ching Lin
- Yu‑Wei Lin
- Yu‑Feng Tian
- Chen‑Yi Lin
- Ming‑Jen Sheu
- Chien‑Feng Li
- Ming‑Hong Tai
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Affiliations: Department of Radiation Oncology, Chi‑Mei Medical Center, Tainan 71069, Taiwan, R.O.C., Division of General Surgery, Department of Surgery, Chi Mei Medical Center, Tainan 71069, Taiwan, R.O.C., Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71069, Taiwan, R.O.C., Department of Pathology, Chi Mei Medical Center, Tainan 71069, Taiwan, R.O.C., Institute of Biomedical Sciences, National Sun Yat‑Sen University, Kaohsiung 80424, Taiwan, R.O.C.
Published online on: November 26, 2018 https://doi.org/10.3892/ol.2018.9756
Pages: 1551-1558
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the prognostic value of cytoplasmic (‑C) and nuclear epidermal growth factor receptor (EGFR‑N) expression in rectal cancer patients following neoadjuvant concurrent chemoradiotherapy (CCRT). A total of 172 newly diagnosed rectal cancer patients post‑neoadjuvant CCRT and curative surgery, treated between January 1998 to December 2008, were included. Pathological tissues used for evaluation were biopsy specimens obtained prior to CCRT, and specimens collected at surgery. EGFR expression in the nucleus and cytoplasm was assessed by immunohistochemistry tests. An intensity of 3+ EGFR reactivity in the cytoplasm (and/or membrane) of tumor cells was defined as overexpression of EGFR‑C. The cutoff percentage of immunoreactive tumor cells for EGFR‑N overexpression was 50%. Expression levels of EGFR‑C and EGFR‑N were further analyzed by clinicopathological features for 5‑year survival disease‑specific survival (DSS), local recurrence‑free survival (LRFS) and metastasis‑free survival (MeFS). The results revealed that 20.9 and 23.3% of the cohort had high EGFR‑N and EGFR‑C expression, respectively. EGFR‑N overexpression was significantly associated with advanced pre‑treatment tumor stage (T3 and 4; P=0.017) and post‑treatment tumor stage (T3 and 4; P<0.001). In univariate analysis, EGFR‑N overexpression was significantly associated with poorer DSS (P=0.0005), MeFS (P=0.0182), and LRFS (P=0.0014). Furthermore, it remained an independent prognosticator of worse DSS [P=0.007, hazard ratio (HR)=2.755] and LRFS (P=0.0164, HR=3.026) in multivariate analysis. Overexpression of EGFR‑N, and not EGFR‑C, may help identify rectal cancer patients who have an increased risk of local recurrence and poor survival following neoadjuvant CCRT.

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