HER2/neu Oncoprotein Overexpression in Epithelial Ovarian Cancer: Evaluation of its Prevalence and Prognostic Significance

Abstract

Introduction: The HER2/neu proto-oncogene encodes a transmembrane receptor protein involved in the development and progression of the majority of cancers. Prior studies have shown that HER2/neu oncogene is overexpressed in approximately 15–30% of ovarian carcinomas. However findings regarding the overexpression and prognosis are still conflicting. Methods: Our retrospective study was performed on 194 ovarian carcinoma tissues obtained at the time of first surgery. The staining procedure for HER2/neu overexpression was performed using a polyclonal antibody. Results: HER2/neu overexpression was found in 53 out of 194 (27.3%) investigated cases of which 26 (13.4%) carcinomas were weakly positive (score 1+) and 27 (13.9%) moderately (score 2+) to intensely positive (score 3+). No significant relationship was found between HER2/neu score and main clinical and pathological features. Significant difference in overall survival was evident between negative women (0/1+) and positive women (2+/3+): 48 and 29 months, respectively (p = 0.04). In multivariate analysis HER2/neu overexpression appeared to be the only variable significantly correlated with progression and death. CA125 normalization at 3 and 6 months appeared a strong predictor of progression and survival. Conclusion: In this study HER2/neu overexpression was associated with an increased risk of progression and death, especially among women with FIGO Stage I and II ovarian carcinoma.

Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?

“…The prognostic role of HER2 overexpression in EOC remains unclear. Some studies proposed that an elevated HER2 level was associated with poorer survival (Lassus et al, 2004;Steffensen et al, 2007), whereas other studies could not demonstrate any association (Verri et al, 2005;Tuefferd et al, 2007). In the meta-analysis conducted by Zhao et al (2013), the prognostic effect of HER2 overexpression was also explored; after reviewing eight studies, they demonstrated that HER2 overexpression was significantly associated with poorer overall survival.…”

Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors

“…Despite the numerous studies on the expression and clinical significance of HER1 (4-6) and HER2 (3,(7)(8)(9), the role of these receptors are still controversial in ovarian cancer. Furthermore, only few studies have described the tissue expression of the HER3 and HER4 receptor protein in ovarian cancer.…”

ΔNp63α is a common inhibitory target in oncogenic PI3K/Ras/Her2-induced cell motility and tumor metastasis

“…Overexpression of Her2 is found in 22% of breast cancers, 28% of pulmonary adenocarcinoma, 17% of colorectal adenocarcinomas, 11% of pulmonary squamous, and 11% of gastric adenocarcinomas (37). Her2 overexpression is also found in ovarian and aggressive forms of uterine cancer (38)(39)(40). Recent evidence has implicated Her2 signaling in resistance to the EGFR-targeted cancer drug cetuximab (41).…”