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In ovarian cancer the prognostic influence of HER2/neu is not dependent on the CXCR4/SDF-1 signalling pathway.

ABSTRACT: HER2/neu overexpression is a driving force in the carcinogenesis of several human cancers. In breast cancer the prognostic influence of HER2/neu was shown to be at least partly based on increased metastatic potential mediated by the chemokine-chemokine receptor pair SDF-1(CXCL12)/CXCR4. We wanted to evaluate the influence of HER2/neu on ovarian cancer prognosis and to investigate whether compromised survival would correlate with CXCR4 expression and/or SDF-1 abundance. Therefore, we analysed HER2/neu, CXCR4, and SDF-1 in 148 ovarian tumour samples by means of immunohistochemistry on tissue microarrays. Overexpression of HER2/neu was found in 27.6% of ovarian cancer tissues and in 15% of ovarian borderline tumours. In ovarian cancer patients, overexpression of HER2/neu correlated closely with overall survival (univariate hazard ratio (HR) 2.59, P=0.005; multiple corrected HR 1.92, P=0.074). In contrast, CXCR4 expression and SDF-1 abundance had no impact on overall survival, and both parameters were not correlated with HER2/neu expression. As expected, cytoplasmic CXCR4 expression and SDF-1 abundance correlated closely (P<0.0001). Our results confirm a univariate influence of HER2/neu expression on overall survival, which was completely independent of the expression of CXCR4 and the abundance of SDF-1, implying significant differences between the HER2/neu downstream pathways in ovarian cancer compared with breast cancer.

SUBMITTER: Pils D

PROVIDER: S-EPMC2360022 | biostudies-other | 2007 Feb

REPOSITORIES: biostudies-other

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Project description:Background:Human epidermal growth factor receptor 2 (HER2) has tyrosine kinase activity and is a member of the epidermal growth factor receptor family. This initiates a variety of signal for pathways which leads to cell proliferation and tumourigenesis. In approximately 15-30% of breast cancers and 10-30% of gastric/gastroesophageal cancers, amplification or overexpression of HER2 occurs, and it serves as a prognostic and predictive biomarker. HER-2/neu is one of the most frequently studied molecular biological parameters in epithelial ovarian cancer (EOC), but its prognostic impact has not been fully assessed. The objective of the current study was firstly to analyse the presence of HER-2 overexpression in EOC patients and secondly to evaluate association between human epidermal growth factor receptor 2 (HER-2/neu) expression and progression-free survival in patients with EOC. Method:In this prospective study of 2 years in our department, 186 gynaecological cancers were operated out of which 98 cases were operated for epithelial ovarian cancer and rest for cervical cancer, endometrial cancer, and other subtypes of ovarian cancer. In this study, HER2 gene status was evaluated in EOC by immunohistochemistry analysis, and overall survival of these patients was evaluated. Results:HER-2 overexpression was found in 22 of the 98 investigated cases (22.45%), in which 14 OC (14.29%) were weakly positive and 8 OC (8.16%) were moderately to intensely positive. In the study, increased HER2 expression was associated with decreased progression-free survival (PFS) and hence poor prognosis (P 0.054). Conclusions:The introduction of HER2-directed therapies has dramatically influenced the outcome of patients with HER2 positive breast and gastric/gastroesophageal cancers. The present study findings provided that HER-2/neu expression in patients with OC has an adverse impact on the PFS. Therefore, our results show that the decision algorithm usually used in breast cancer by HER2 may be appropriate in ovarian cancer.

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In ovarian cancer the prognostic influence of HER2/neu is not dependent on the CXCR4/SDF-1 signalling pathway.

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