Prognostic Significance of HER3 Expression in Patients with Cervical Cancer

Abstract

HER3 has been recognized to have an oncogenic role in various types of cancer. However, its prognostic significance has not been elucidated in cervical cancer. The aim of this study was to investigate the prognostic significance of HER3 expression in cervical cancer using immunohistochemistry (IHC). HER3 immunohistochemical staining was performed on the tumor tissue samples of 336 cervical cancer patients. The association between the clinicopathological characteristics and patient survival analysis was assessed according to HER3 expression. HER3 IHC staining was positive in 31.0% (104/336) of the cervical cancer patients. A higher proportion of adeno-/adenosquamous carcinoma was observed in the HER3-positive group (34.6%) than in the HER3-negative group (18.8%). In survival analysis, HER3 expression was significantly associated with poorer disease-free survival (DFS) and overall survival (OS) (p < 0.001 and p = 0.002, respectively). Multivariate analysis also indicated that HER3 expression was an independent prognostic factor for DFS (hazard ratio (HR) = 2.58, 95% confidence interval (CI) 1.42–4.67, p = 0.002) and OS (HR = 3.21, 95% CI, 1.26–8.14, p = 0.014). HER3 protein expression was a poor prognostic factor of survival in patients with cervical cancer. This finding could help to provide individualized management for these patients.

Changes in HER3 expression profiles between primary and recurrent gynecological cancers

“…HER3 plays many roles in cancer cells, including mediating cell transformation and tumor malignancy [45,46]. Cancer patients with high HER3 expression are reported to have poorer prognoses in several cancer types [10][11][12][13][14][15]. Our results indicate that increased HER3 expression at recurrence may be associated with an inferior prognosis (Fig.…”

“…In gynecological cancers, the incidence of HER3 overexpression was reported to be 41.3-67.5% for ovarian cancer [5,27,28], 30% for endometrial cancer [29], and 31.0-74.7% for cervical cancer [15,[30][31][32]. However, most studies have only reported the incidence of HER3 expression at initial diagnosis, while that at recurrent diagnosis was not evaluated.…”

Changes in HER3 expression profiles between primary and recurrent gynecological cancers

“…HER3 plays many roles in cancer cells, including mediating cell transformation and tumor malignancy [ 46 , 47 ]. Cancer patients with high HER3 expression are reported to have poorer prognoses in several cancer types [ 10 – 15 ]. Our results indicate that increased HER3 expression at recurrence may be associated with an inferior prognosis (Fig.…”

“…It heterodimerizes with receptor tyrosine kinases to activate oncogenic signaling via the the phosphatidylinositol 3-kinase/protein kinase B pathway [ 1 , 2 ]. Overexpression of HER3 is observed in several cancers [ 3 – 9 ] and is associated with inferior prognosis [ 10 – 15 ]. In addition, several reports have suggested a pathogenic role for HER3 in mechanisms underlying primary or acquired resistance to EGFR inhibitors [ 16 – 18 ] and anti-HER2 therapies [ 19 ].…”

“…In gynecological cancers, the incidence of HER3 overexpression was reported to be 41.3–67.5% for ovarian cancer [ 5 , 27 , 28 ], 30% for endometrial cancer [ 29 ], and 31.0–74.7% for cervical cancer [ 15 , 30 – 32 ]. However, most studies have only reported the incidence of HER3 expression at initial diagnosis, while that at recurrent diagnosis was not evaluated.…”