The growth factor receptors HER-2/neu and EGFR, their relationship, and their effects on the prognosis in early stage (FIGO I-II) epithelial ovarian carcinoma

Abstract

Epithelial ovarian cancer is a heterogeneous disease and many biologic and molecular factors are important for its development and progression, including growth rate, metastatic potential, chemo- and radiosensitivity, and prognosis. Even in the early stages (FIGO I-II), many questions persist about the biologic behavior, optimal treatment, and prognosis. In a series of 106 patients with epithelial ovarian cancers in FIGO stages IA-IIC, a number of known prognostic factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to two important growth factor receptors for oncogenesis (HER-2/neu and EGFR). Immunohistochemical techniques were used. All patients received adjuvant radiotherapy 4-6 weeks after the primary surgery. In a univariate analysis, the expression of the HER-2/neu receptor was not associated with any of the clinicopathologic factors studied or survival status. Positive EGFR staining was associated with poor survival in a univariate analysis. Co-expression of HER-2/neu and EGFR was most frequently seen in serous tumors and positive staining for HER-2/neu alone was associated with mucinous tumors. Both endometrioid and clear cell tumors belonged to the largest subgroup with concomitant negativity for both HER-2/neu and EGFR. In a multivariate Cox analysis, the tumor grade and EGFR status of the tumors were independent and significant prognostic factors. A therapeutic strategy for epithelial ovarian cancer might be to decrease EGFR expression by gene therapy in combination with adjuvant radiotherapy or chemotherapy.

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

“…The results of the studies evaluating the prognostic role of EGFR expression are also conflicting. Some studies suggested EGFR positivity as a negative prognostic factor (Skirnisdottir et al, 2001;Psyrri et al, 2005;Lassus et al, 2006;Noske et al, 2011) and demonstrated an association with poorer survival rates, while others reported no relationship between disease outcome and EGFR expression (Nielsen et al, 2004;de Graeff et al, 2008). Variations in IHC procedures, antibodies, and patient selection may provide some explanation for the differing results from these studies.…”

“…In contrast to breast cancer, relatively few reports evaluating the importance of receptor expressions and EOC subtypes exist in the literature and demonstrate contradictory results (Hogdall et al, 2007;Liu et al, 2010;Sinn et al, 2011;Chumworathayi, 2013;Zhao et al, 2013). EGFR expression was also suggested to be related to worse prognosis in a few studies (Skirnisdottir et al, 2001;Noske et al, 2011). In this study, besides traditional clinicopathologic parameters, we evaluated the prognostic and predictive effects of hormone receptor, HER2 and EGFR expressions on EOC prognosis separately, also their correlations and associations with platinum sensitivity.…”

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

“…Most published studies regarding HER1 have been performed on malignant tumor tissue and the vast majority of these studies measured HER1 expression using immunohistochemistry. HER1 overexpression has been reported in between 17-57% of the examined cases (4,5,(30)(31)(32)(33). Two studies have investigated the HER1 expression in benign ovarian tissue.…”

Lack of relationship between EGFR-1 immunohistochemical expression and prognosis in a multicentre clinical trial of 93 patients with advanced primary ovarian epithelial cancer (GINECO group)

“…However, regarding ovarian carcinomas, its prognostic value still remains debated in the literature, showing for some studies a poor A B (Scambia et al, 1992(Scambia et al, , 1995Fischer-colbrie et al, 1997;Skirnisdottir et al, 2001), whereas others showed no influence of EGFR-1 overexpression on patient's outcome (Van der Burg et al, 1993;Meden et al, 1995;Bartlett et al, 1996;Baekelandt et al, 1999). Only one study in the literature (Bauknecht et al, 1988) showed a favourable prognostic role of EGFR-1 overexpression, but no multivariate analysis was presented.…”