HER2 over-expressing high grade endometrial cancer expresses high levels of p95HER2 variant

Growdon, W.B.; Byron, Virginia F.; DiGloria, Celeste M.; Borger, Darrell R.; Foster, Rosemary; Winslow, John; Sperinde, Jeffery; Rueda, Bo R.

doi:10.1016/j.ygyno.2014.11.034

Cited by 9 publications

(9 citation statements)

References 24 publications

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“…A reclassification of risk based on the molecular features is strongly needed for EC subgroups, such as the high-grade (G3) EEC, that have never been clearly classified according to dualistic model of EC. [31][32][33][34] Over the last 3 years, few groups 11,[35][36][37][38] have investigated the prognostic value of different molecular alterations involved in endometrial carcinogenesis, demonstrating that the genomic features of ECs allow for a more reproducible and accurate risk reclassification, which may help in choosing the most appropriate surgical and adjuvant treatment for women with aggressive tumors.…”

Section: Discussionmentioning

confidence: 99%

DJ-1 is a reliable serum biomarker for discriminating high-risk endometrial cancer

et al. 2017

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New reliable approaches to stratify patients with endometrial cancer into risk categories are highly needed. We have recently demonstrated that DJ-1 is overexpressed in endometrial cancer, showing significantly higher levels both in serum and tissue of patients with high-risk endometrial cancer compared with low-risk endometrial cancer. In this experimental study, we further extended our observation, evaluating the role of DJ-1 as an accurate serum biomarker for high-risk endometrial cancer. A total of 101 endometrial cancer patients and 44 healthy subjects were prospectively recruited. DJ-1 serum levels were evaluated comparing cases and controls and, among endometrial cancer patients, between high- and low-risk patients. The results demonstrate that DJ-1 levels are significantly higher in cases versus controls and in high- versus low-risk patients. The receiver operating characteristic curve analysis shows that DJ-1 has a very good diagnostic accuracy in discriminating endometrial cancer patients versus controls and an excellent accuracy in distinguishing, among endometrial cancer patients, low- from high-risk cases. DJ-1 sensitivity and specificity are the highest when high- and low-risk patients are compared, reaching the value of 95% and 99%, respectively. Moreover, DJ-1 serum levels seem to be correlated with worsening of the endometrial cancer grade and histotype, making it a reliable tool in the preoperative decision-making process.

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Section: Discussionmentioning

confidence: 99%

DJ-1 is a reliable serum biomarker for discriminating high-risk endometrial cancer

et al. 2017

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“…Retrospective data in patients with HER2 amplified breast cancer revealed that patients with truncated p95HER2 were less responsive to HER2 therapy with trastuzumab [24]. Data recently presented at the Society for Gynecologic Investigation suggested that p95HER2 commonly occurs in patients with uterine serous carcinoma [25]. Other reports have suggested that HER2/neu amplified uterine serous carcinomas have the ability to shed soluble free receptor into the interstitial milieu [26].…”

Section: Discussionmentioning

confidence: 99%

Neratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo

Schwab

English

Roque

et al. 2014

Gynecologic Oncology

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“…Firstly, the binding of therapeutic anti‐HER‐2 antibodies on HER‐2 ECD neutralizes the biological activity of trastuzumab . Furthermore, amounts of HER‐2 ECD shedding leaves a truncated HER‐2 form (p95) with constitutive kinase activity that can provide ligand‐independent growth and survival signals to the cells . Therefore, serum HER‐2 ECD could be a biomarker that helps to identify the subgroup of poorer outcome among HER‐2 overexpression breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Elevated serum HER‐2 predicts poor prognosis in breast cancer and is correlated to ADAM10 expression

et al. 2019

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Human epidermal growth factor receptor‐2 (HER‐2) overexpression in breast tumor tissues is associated with a poor prognosis but may benefit from treatment with trastuzumab. The extracellular domain (ECD) of HER‐2 can be measured in serum and which has been a new inspection item in clinical laboratory of several hospitals. However, whether serum HER‐2 ECD can be a marker of HER‐2 status in tumor tissues still confused clinicians. This study is a retrospective observation to explore the correlation between serum HER‐2 ECD shedding and tissue HER‐2 status in breast cancer patients. Meanwhile, we will further uncover the potential clinical significance of serum HER‐2 ECD detection. A total of 545 unselected breast cancer patients from Fudan University Shanghai Cancer Center were enrolled in this study. At primary diagnosis without any treatment, serum HER‐2 ECD was measured on ADVIA Centaur assay; meanwhile, tissue HER‐2 from core needle biopsy was tested through immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). We showed that serum HER‐2 ECD concentration was related to tissue HER‐2 status. Nevertheless, 36.9% of patients with tissue HER‐2 overexpression had low levels of HER‐2 ECD shedding (<15 ng/mL) in serum. Here, we demonstrated that HER‐2 ECD shedding was also associated with protein expression and alpha‐secretase activity of a disintegrin and metalloproteinase 10 (ADAM10) using tumor tissues and cell lines. Progression‐free survival (PFS) data from breast cancer patients in TNM phase II and III with tissue HER‐2 IHC 3+ were analyzed using Kaplan‐Meier plotter. The patients with serum HER‐2 ECD above 15 ng/mL had lower progression‐free survival than those with serum HER‐2 ECD <15 ng/mL. Thus, serum HER‐2 ECD could be a biomarker to identify the subgroup of poorer outcome among HER‐2 overexpression breast cancer patients. Inhibition of ADAM10 activity may have potential therapeutic benefit for this most aggressive tumor subgroup.

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HER2 over-expressing high grade endometrial cancer expresses high levels of p95HER2 variant

Cited by 9 publications

References 24 publications

DJ-1 is a reliable serum biomarker for discriminating high-risk endometrial cancer

DJ-1 is a reliable serum biomarker for discriminating high-risk endometrial cancer

Neratinib shows efficacy in the treatment of HER2/neu amplified uterine serous carcinoma in vitro and in vivo

Elevated serum HER‐2 predicts poor prognosis in breast cancer and is correlated to ADAM10 expression

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