Prognostic Significance of c-erbB-2 mRNA in Ovarian Carcinoma

Berno, Tamara; Kreutz, Elisabeth; Weikel, W.; Meinert, Rolf; Oesch, Franz; Knapstein, P.; Becker, Roger

doi:10.1006/gyno.1996.0226

Cited by 42 publications

(33 citation statements)

References 14 publications

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“…3237 The most recent study also correlated HER-2/neu protein immunoreactivity with response to platin-based chemotherapy. 37 The results of the present study are comparable to other published studies that also reported an increased rate of HER-2/neu gene or protein abnormalities in ovarian Fan et al 27 Fajac et al (a) 28 Fajac et al (b) 28 Wong et al 29 Tanner et al 30 Meden et al 31 Felip carcinomas vs tumors of low malignant potential. The present data also are comparable to the majority of published studies that have failed to find a significant association between UER-2/neu gene or protein abnormalities with survival in ovarian cancer.…”

Section: Discussionsupporting

confidence: 81%

HER-2/neuOncogene Amplification by Fluorescence In Situ Hybridization in Epithelial Tumors of the Ovary

et al. 1999

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Section: Discussionsupporting

confidence: 81%

HER-2/neuOncogene Amplification by Fluorescence In Situ Hybridization in Epithelial Tumors of the Ovary

et al. 1999

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“…Additionally, there is some variability by histology [378][379][380]451,460], with recent data supporting a higher frequency of both gene amplification and HER2/neu overexpression in the mucinous subset of ovarian epithelial carcinomas [380][381][382][383] and in 60% to almost 100% of Müllerian tumors [448][449][450]. Generally, for ovarian epithelial neoplasms, HER2/neu overexpression or gene amplification is considered a poor prognostic factor [392][393][394][395][396][397][398][399][400][401][402]451,453], although not a particularly strong prognostic factor, and gene amplification may be a better prognostic indicator [453].…”

Section: Ovarianmentioning

confidence: 99%

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

Nelson¹

2014

Clinical Investigation

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No biological molecule in the field of oncology has been more extensively or more successfully targeted for therapeutic intent than the product of the c-erbB2 gene, HER2/neu. This is the second of a comprehensive three-part review of the foundation for and therapeutic targeting of HER2/neu. The distribution of HER2/neu overexpression and/or gene amplification by individual tumor sites and histologies will be comprehensively surveyed and described. This provides a bridge between the primarily basic science focused Part I, and the survey of clinical applications to follow in Part III. In combination, this comprehensive survey will identify opportunities and promising areas for future evaluation of HER2/neu-targeted therapies, highlighting the importance of HER2/neu as an increasingly important therapeutic target.

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“…1) that are involved in the transmission of proliferative as well as differentiation signals (2,3). ERBB2 plays an important role in the development of human epithelial neoplasias and high levels of ERBB2 expression correlate with poor prognosis in breast and ovarian carcinoma (4,5). Overexpression of the receptor was not only described in human breast and ovarian carcinomas (6), but also in other types of cancer, e.g., bladder carcinoma (7), non-small cell lung cancer (8), in tumors of the gastrointestinal tract (9), as well as in other human malignancies (10).…”

Section: Introductionmentioning

confidence: 99%

ERBB2-Mediated Transcriptional Up-regulation of the α5β1 Integrin Fibronectin Receptor Promotes Tumor Cell Survival Under Adverse Conditions

et al. 2006

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Oncogenic activation of the receptor tyrosine kinase ERBB2 is a key event in the development of a number of epithelial malignancies. In these tumors, high levels of ERBB2 are strongly associated with metastatic disease and poor prognosis. Paradoxically, an inherent cellular response to hypermitogenic signaling by ERBB2 and other oncogenes seems to be growth arrest, rather than proliferation. Molecular characterization of this yet undefined antiproliferative state in independent cell lines overexpressing either wild-type ERBB2 or the mutationally activated receptor unveiled a dramatic induction of the A5B1 integrin fibronectin receptor. A5 Integrin up-regulation is mainly a transcriptional response mediated by the hypoxia-inducible transcription factors (HIF), leading to a massive increase in membrane-resident receptor molecules and enhanced fibronectin adhesiveness of the respective cells. Functionally, ERBB2-dependent ligation of fibronectin results in improved survival of mammary adenocarcinoma cells under adverse conditions, like serum withdrawal, hypoxia, and chemotherapy. HIF-1A is an independent predictor of poor overall survival in patients with breast cancer. In particular, HIF-1A overexpression correlates significantly with early local relapse and distant metastasis, a phenotype also highly characteristic of ERBB2-positive tumors. As HIF-1A is known to be stabilized by ERBB2 signaling under normoxic conditions, we propose that A5 integrin is a major effector in this regulatory circuit and may represent the molecular basis for the HIF-1A-dependent aggressiveness observed in ERBB2-overexpressing breast carcinomas. Hypermitogenic ERBB2 signaling and tumor hypoxia may act synergistically to favor the establishment of chemoresistant dormant micrometastatic cells frequently observed in patients with breast cancer. This new insight could be the basis for additional approaches complementing current cancer therapy. (Cancer Res 2006; 66(7): 3715-25)

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Prognostic Significance of c-erbB-2 mRNA in Ovarian Carcinoma

Cited by 42 publications

References 14 publications

HER-2/neuOncogene Amplification by Fluorescence In Situ Hybridization in Epithelial Tumors of the Ovary

HER-2/neuOncogene Amplification by Fluorescence In Situ Hybridization in Epithelial Tumors of the Ovary

HER2/neu: an increasingly important therapeutic target. Part 2: Distribution of HER2/neu overexpression and gene amplification by organ, tumor site and histology

ERBB2-Mediated Transcriptional Up-regulation of the α5β1 Integrin Fibronectin Receptor Promotes Tumor Cell Survival Under Adverse Conditions

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