Serum Levels of Shed Her2/Neu Protein in Men With Prostate Cancer Correlate With Disease Progression

Osman, Iman; Mikhail, Maryann; Shuch, Brian; Clute, Megan; Cheli, Carol D.; Ghani, Farooq; Thiel, Robert; Taneja, Samir S.

doi:10.1097/01.ju.0000181205.23233.65

Cited by 38 publications

(47 citation statements)

References 16 publications

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“…Furthermore, in prostate cancer cell lines, we found that androgen-sensitive LNCaP cells and castration-resistant C4-2 cells also overexpressed this protein (Figure 3). Our findings are consistent with the majority of patient-related reports in literature, [5][6][7][8]10,11 as well as some in vitro and animal model studies. 13,48,49 Furthermore, it has been recently reported that in men with long-term follow-up after HER-2 targeting of prostate cancer K-x Zhang et al radical prostatectomy, HER-2 expression when combined with percentage DNA index can be used clinically for prediction of progression, metastasis and prostate cancerspecific death.…”

Section: Discussionsupporting

confidence: 93%

“…In prostate cancers, overexpression of HER-2 has been reported to be associated with progression to androgen independence, [5][6][7][8]10,11 although some contradictory results have also been reported. 39,40 To normalize variables such as fixation and staining procedures, which could account for the reported differences, we used a TMA approach where 105 unique prostate tissue cores from 35 patients were immunostained for HER-2 simultaneously.…”

Section: Resultsmentioning

confidence: 99%

“…[5][6][7][8][9][10][11] Overexpression of HER-2, which causes activation of the PI3k/AKT pathways and promotion of cell proliferation, has been proposed to be a survival factor for prostate cancer cells in the absence of androgens. 10,12 Moreover, this can lead to the activation of the androgen receptor and enhancement of binding of this nuclear receptor to the promoters of androgenregulated genes.…”

Section: Introductionmentioning

confidence: 99%

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Lentiviruses with trastuzumab bound to their envelopes can target and kill prostate cancer cells

Moussavi

et al. 2009

Cancer Gene Ther

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In this study, we took advantage of the overexpression of human epidermal growth factor receptor 2 (HER-2) in prostate cancers to design lentiviruses with modified envelope proteins that bind antibodies to specific cell-surface antigens. When bound to trastuzumab (Herceptin, Genentech, CA), lentiviruses were able to selectively infect androgen-sensitive LNCaP and castrationresistant C4-2 human prostate cancer cell lines, both of which express high levels of HER-2. To test for a therapeutic effect, we engineered our antibody-binding lentiviruses to express thymidine kinase, which can convert the non-toxic pro-drug ganciclovir (GCV) into a cytotoxic form. LNCaP and C4-2 cells infected by these viruses were sensitive to GCV killing. In vivo, C4-2 xenograft tumors treated either intratumorally or i.v. with trastuzumab-bound lentivirus expressed luciferase, although the latter route was less tumor specific. When a prostate-specific promoter for governing luciferase expression was combined with trastuzumab-mediated delivery, there was a further enrichment in targeting viral gene expression in prostate tumors. In conclusion, we found that although prostate cancers that express high levels of HER-2 are resistant to the killing effects of trastuzumab, they can be targeted for selective gene expression and destruction by viruses with envelope proteins engineered to bind this antibody.

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Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lentiviruses with trastuzumab bound to their envelopes can target and kill prostate cancer cells

Moussavi

et al. 2009

Cancer Gene Ther

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“…[6][7][8] The serum levels of HER2/neu ECD protein have been found to be elevated in advanced , hormone-resistant prostate cancer. 4 In addition, we found that a high level of pretreatment serum HER2/neu ECD protein is associated with a high risk of biochemical recurrence after endocrine therapy in patients with metastatic prostate cancer. 5 The ECD of the HER2/neu protein can be cleaved from the cell surface by matrix metalloproteases and then released into the blood.…”

Section: Discussionmentioning

confidence: 82%

“…2 The ECD is shed into the blood stream, and clinical research in prostate cancer has shown that elevated serum levels of circulating HER2/neu ECD were correlated with hormone-refractory disease after endocrine therapy. 3,4 Also, our previous study showed that measuring the pretreatment serum level of HER2/neu ECD of patients with metastatic prostate cancer might be useful in predicting biochemical recurrence after endocrine therapy. 5 Meanwhile, several investigations have shown that overexpression of HER2/neu by immunohistochemical study might be a factor for an unfavorable prognosis in patients with prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Comparison of serum HER2/neu with immunohistochemical HER2/neu expression for the prediction of biochemical progression in metastatic prostate cancer

Tambo¹,

Higashihara²,

Terado

et al. 2009

Int J of Urology

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Objectives: To examine whether pretreatment serum human epidermal growth factor receptor 2 (HER2/neu) and immunohistochemical HER2/neu expression predict biochemical recurrence-free survival in advanced prostate cancer. Methods: We studied 75 untreated patients with metastatic prostate cancer and compared them to a control group of 97 patients without histologically diagnosed prostate cancer. Serum samples were collected for HER2/neu protein analysis before the patients started endocrine therapy. HER2/neu expression in the prostate tissue was evaluated using immunohistochemical analysis. Results: Serum concentration of HER2/neu in patients with prostate cancer was significantly higher than in those without cancer (P = 0.005). Based on the median HER2/neu value, a cut-off level of 12.5 ng/mL was established to separate low from high serum HER2/neu levels. The biochemical recurrence-free survival rate was significantly lower in patients with a high serum HER2 level (P < 0.001). HER2/neu overexpression was found in 18 patients (24%) by immunohistochemical analysis. Biochemical recurrence-free survival rates did not show a statistically significant difference between HER2/neu positive and negative groups. Multivariate analysis showed that the pretreatment serum HER2/neu value was an independent predictor of biochemical recurrence (P = 0.02). Conclusions: Pretreatment serum HER2/neu may represent a more valuable tool than immunohistochemical HER2/neu expression for the prediction of biochemical recurrence in metastatic prostate cancer patients.

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Reply: Sacralization is not associated with elongated cervical costal process and cervical rib

et al. 2011

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Serum Levels of Shed Her2/Neu Protein in Men With Prostate Cancer Correlate With Disease Progression

Cited by 38 publications

References 16 publications

Lentiviruses with trastuzumab bound to their envelopes can target and kill prostate cancer cells

Lentiviruses with trastuzumab bound to their envelopes can target and kill prostate cancer cells

Comparison of serum HER2/neu with immunohistochemical HER2/neu expression for the prediction of biochemical progression in metastatic prostate cancer

Reply: Sacralization is not associated with elongated cervical costal process and cervical rib

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