Pretreatment serum level of HER2/nue as a prognostic factor in metastatic prostate cancer patients about to undergo endocrine therapy

Abstract

Background: Overexpression of the HER2 receptor protein and amplification of the HER2 gene has been implicated in tumor development and progression, and has been associated with a poor prognosis in several types of cancer. The aim of this study was to evaluate whether pretreatment serum HER2 levels can be used to predict biochemical recurrence-free survival in prostate cancer patients about to undergo endocrine therapy. Methods:The study population consisted of 379 untreated patients with histologically diagnosed prostate cancer: 197 with T2N0M0, 93 with T3N0M0, 19 with TxN1Mx, and 70 with TxNxM1. Serum HER2 levels were assessed in the prostate cancer patients prior to treatment as well as in a control group of 100 patients with histologically confirmed non-cancer. Biochemical recurrence-free curves for the patients were investigated separately using the Kaplan-Meier method. Results:The mean level of HER2 in serum was significantly higher in prostate cancer patients than non-prostate cancer patients (P = 0.006). Also, the serum HER2 level was significantly higher in bone metastatic cancer patients (14.3 ± 6.3 ng/mL) than in non-metastatic patients (T2: 11.9 ± 2.3 ng/mL, P = 0.003; T3: 12.2 ± 2.8 ng/mL, P = 0.011). The metastatic patients were divided into those with low and high HER2 levels using a cutoff value of 12.6 ng/mL based on receiver-operating characteristic curves. The biochemical recurrence-free rate was significantly poorer in patients with a high HER2 level (P = 0.0078, log-rank test).Multivariate Cox logistic regression analysis demonstrated that the pretreatment serum HER2 value (P = 0.022), serum prostatespecific antigen value (P = 0.018), and extent of disease score (P = 0.027) were independent predictors of recurrence. Conclusions:The pretreatment serum HER2 level may be a useful independent prognostic factor that is associated with a high risk of biochemical recurrence in metastatic prostate cancer patients about to undergo endocrine therapy.

Beyond prostate-specific antigen: alternate serum markers

“…135 Expression of other TGF receptors, namely epidermal growth factor receptor (EGFR) and human epidermal receptor 2 (HER2/nue), may correlate with disease progression and hormone-refractory disease. 136 A recent report revealed that serum EGFR measurements increased the PSA vs alternate serum markers ML Ramírez et al PSA vs alternate serum markers ML Ramírez et al ability to predict positive biopsies, and levels were significantly associated with those of u-PAR. 43 Detection of CaP-specific genes using variations of PCR methods has identified numerous biomarkers in tissue and bodily fluids.…”

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

“…In our previous study, a high level of serum HER2/neu indicated a shorter interval until biochemical recurrence after endocrine therapy in patients with metastatic prostate cancer with a mean follow-up of 20.3 months. 5 This study extended the mean period of follow up to 30.8 months, and evaluated by both serum analysis and immunohistochemical assay. In this study, measurement of the serum HER2/neu level proved to be more useful as an indicator of biochemical recurrence after endocrine therapy in patients with metastatic prostate cancer than the expression of HER2/neu by IHC on multivariate analysis.…”

“…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. 13 The clinical or biological significance of HER2/neu ECD shedding is unknown, but it is probably attributable to the up-regulation of metalloproteases, which are involved in proteolytic cleavage of HER2/neu and have been linked to tumor invasion and metastasis.…”

“…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. [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.…”

Gefitinib and bicalutamide show synergistic effects in primary cultures of prostate cancer derived from androgen-dependent naive patients

“…On the other hand, the establishment of new biomarkers is needed to identify high-risk patients as candidates for new (adjuvant) therapies and to find new surrogate endpoints to assess the efficacy of these treatments (1). In the past 10 years, conflicting results on HER-2/neu expression in prostate cancer were reported (2)(3)(4)(5)(6)(7)(8). Furthermore, it was proposed that Her2 and androgen receptors function synergistically in the absence of androgens (9)(10)(11).…”