Prognostic significance of immunohistochemical expression of the HER-2/neu oncoprotein in bone metastatic prostate cancer

Nishio, Yoshitaka; Yamada, Yoshiaki; Kokubo, Hiroto; Nakamura, Kogenta; Aoki, Shigeyuki; Taki, Tomohiro; Honda, Nobuaki; Nakagawa, Atsuko; Saga, Shinsuke; Hara, Kazuo

doi:10.1016/j.urology.2006.01.060

Cited by 32 publications

(26 citation statements)

References 22 publications

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“…Clinical and biochemical factors, such as lower PS, pain score, EOD on bone scan, lower pretreatment serum testosterone levels, higher serum ALP and acid phosphatase levels, higher PSA levels, and lower HGB levels, have all been reported to be associated with treatment response or patient survival [12]. Pathological and immunohistochemical studies have also shown that nuclear texture, oligosaccharide sialyl Lewis (x), c-erbB-2 (Her2/neu) and tissue factor could be predictors of survival [13]. In this study, ApoC-I levels were found to be increased in the sera of metastatic prostate cancer patients whose disease progressed from an androgen-dependent state to an androgen-independent phase.…”

Section: Discussionmentioning

confidence: 99%

The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

Yamamoto-Ishikawa¹,

Suzuki²,

Nezu³

et al. 2009

Asian J Androl

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Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients' sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points: point A, pre-treatment; point B, at the nadir of the prostatespecific antigen (PSA) level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients' sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I (ApoC-I). Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-I protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.

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Section: Discussionmentioning

confidence: 99%

The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

Yamamoto-Ishikawa¹,

Suzuki²,

Nezu³

et al. 2009

Asian J Androl

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“…6 The discrepancy of these results in IHC studies on HER2/neu may be a reflection of the short follow-up period and small proportion of enrolled patients.…”

Section: Discussionmentioning

confidence: 99%

“…1 Several investigators have reported that overexpression of HER2/neu by IHC analysis is association with androgen independence and decreased survival. [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.…”

Section: Discussionmentioning

confidence: 99%

“…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. [6][7][8] However, to our knowledge, there have been no previous reports that have compared serum analysis with the immunohistochemical study of HER2/neu as a predictor of biochemical recurrence after endocrine therapy in advanced prostate cancer. We examined the clinical usefulness of measuring pretreatment serum HER2/neu levels as well as performing an immunohistochemical study of HER2/neu.…”

Section: Introductionmentioning

confidence: 99%

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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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“…We had previously reported that Wwox restoration suppressed prostate cancer cell growth (6). The ErbB2 receptor tyrosine kinase has been found to be elevated in prostate cancer tissues (14,(23)(24)(25)(26)(27)(28), and overexpression of ErbB2 led to androgen-independent cell proliferation through modulation of the AR signal pathway and decreased tumor latency of xenografts in castrated mice (12,15). We hypothesized that Wwox might suppress prostate cancer cell growth by down-modulating ErbB2/AR signaling.…”

Section: Wwox Suppresses Ap2c/erbb2 -Induced Lncap Cell Growth In Lowmentioning

confidence: 99%

Wwox Suppresses Prostate Cancer Cell Growth through Modulation of ErbB2-Mediated Androgen Receptor Signaling

Qin

Iliopoulos

Nakamura

et al. 2007

Molecular Cancer Research

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The expression of the WWOX tumor suppressor gene is lost or reduced in a large fraction of various cancers, including prostate cancer. We previously reported that Wwox overexpression induced apoptosis and suppressed prostate cancer growth in vitro and in vivo. In this study, pathways through which Wwox contributes to control of prostate cancer cell growth have been investigated. We found that Wwox interacts with Ap2; and prevents it from entering the nucleus to bind the ERBB2 promoter region to activate transcription of ERBB2, a mediator of androgen receptor activity and prostate cancer cell growth at limiting androgen concentration. Ectopic expression of Wwox reduced ErbB2 protein expression in vitro and expression of Wwox protein inversely correlated with expression of ErbB2 protein in prostate cancer tissues. Furthermore, Wwox suppressed Ap2;/ErbB2 -induced prostate cancer cell growth and suppressed prostate-specific antigen secretion through interaction with Ap2; and down-modulation of ErbB2, an effect that required functional androgen receptor. (Mol Cancer Res 2007;5(9):957 -65)

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Prognostic significance of immunohistochemical expression of the HER-2/neu oncoprotein in bone metastatic prostate cancer

Cited by 32 publications

References 22 publications

The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

The isolation and identification of apolipoprotein C-I in hormone-refractory prostate cancer using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry

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

Wwox Suppresses Prostate Cancer Cell Growth through Modulation of ErbB2-Mediated Androgen Receptor Signaling

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