Human epidermal growth factor receptor-2 expression in locally advanced rectal cancer: association with response to neoadjuvant therapy and prognosis

Abstract

The aim of this study was to determine whether pretreatment status of human epidermal growth factor receptor-2 (HER-2) could predict pathologic response to neoadjuvant chemoradiotherapy (nCRT) and outcomes for patients with locally advanced rectal cancer (LARC). A total of 119 patients diagnosed with LARC received standardized multimodal treatment. Their HER-2 status was determined in pretreatment biopsies by immunohistochemistry (IHC) and FISH. Tumor response was assessed in resected regimens using the tumor regression grade system and TNM staging system. Twenty-two cases in 119 patients assessed as IHC3+ or IHC2+ plus gene-amplified were determined as HER-2 positive. Positive HER-2 status was not associated with any pretreatment clinicopathologic parameters (P > 0.05). HER-2 status could not predict pathologic response to nCRT based on downstaging (P = 0.210) and tumor regression grade (P = 0.085) but it provides us with a trend that HER-2-positive tumors may be resistant to nCRT. Positive HER-2 status was significantly associated with poor 5-year disease-free survival (P = 0.015) and 5-year overall survival (P = 0.026). It can act as a worse prognostic factor for LARC patients.

Keywords: HER-2; neoadjuvant chemoradiotherapy; rectal cancer; survival; tumor response.

Figure 1

Immunohistochemical staining for human epidermal growth factor receptor-2 (HER-2) in rectal cancer cells. (a) No staining observed (0). (b) Faint staining detected in >10% of tumor cells (1+). (c) Moderate staining observed in >10% of tumor cells (2+). (d) Strong staining observed in >10% of tumor cells (3+). Magnification, ×400.

Figure 2

Fluorescence in situ hybridization in rectal cancer cells. (a) Tumors showed no HER-2 amplification. (b) Tumors showed HER-2 amplification with a HER-2/CEP17 ratio >2.0. Magnification, ×400.

Figure 3

Kaplan–Meier estimates of disease-free survival (DFS) and overall survival (OS) rates in relation to human epidermal growth factor receptor-2 (HER-2) status. (a) HER-2 positivity in rectal cancers correlate with a shorter DFS curves (P = 0.015). (b) HER-2 positivity in rectal cancers correlate with a shorter OS curves (P = 0.026).