Type 1 Protein Tyrosine Kinases in Chinese Breast Carcinomas

Suo, Zhenhe; Yang, Huihua; Mei, Qiang; Skovlund, Eva; Cui, Jiujie; Nesland, Jahn M.

doi:10.1177/106689690100900303

Cited by 12 publications

(13 citation statements)

References 52 publications

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“…However, as mentioned before, its expression correlated with survival of bladder cancer patients, especially when coexpressed with HRG4. These results are consistent with the studies in bladder cancer (Chow et al, 2001) and most of the reports in breast cancer (Knowlden et al, 1998;Suo et al, 1998Suo et al, , 2001Kew et al, 2000), showing HER4 expression to be a good prognostic indicator. In addition, studies of breast cancer cell lines have demonstrated that the antiproliferative and differentiation responses of HER4 are HRG dependent and correlate with HER4 activation (Sartor et al, 2001).…”

Section: Discussionsupporting

confidence: 82%

Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients

et al. 2004

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The epidermal growth factor system has been associated to prognosis in patients with bladder cancer based mainly on the expression of the epidermal growth factor (EGF) receptor 1 (EGFR) and HER2 and their activating ligands. Since limited information exists concerning the expression of other parts of the EGF system, we examined the expression of the receptors HER3 and HER4 and their activating ligands, the heregulins (HRGs), in bladder cancer patients. Biopsies from bladder cancer tumours were obtained from 88 patients followed for a median of 23 months (range, 1 -97 months). The mRNA content of four ligands and their isoforms (HRG1a, HRG1b, HRG2a, HRG2b, HRG3 and HRG4) and two receptors (HER3 and HER4) was quantified by real-time PCR. A significantly lower mRNA expression level of HER3 (P ¼ 0.0003), HRG2a (P ¼ 0.0159), HRG2b (P ¼ 0.0007) and HRG4 (Po0.0001) was observed in muscle-invasive (T2 -T4) tumours as compared to superficial (Ta) tumours. The expression of HER3 mRNA correlated strongly to overall survival (P ¼ 0.0042); increased expression of HER4 (P ¼ 0.0261) and HRG4 (P ¼ 0.0245) was also associated with better prognosis. Interestingly, patients with coexpression of HER3 (P ¼ 0.0034) or HER4 (P ¼ 0.0080) together with their stimulating ligand HRG4 showed even better survival than for HER3 or HER4 alone. Our results together with previous data suggest a dual face for the EGF system. While it is well established that an increased signalling through HER1 and HER2 is related to a poor prognosis, our data suggest that signalling through HER3 and HER4 is related to a favourable outcome in bladder cancer patients.

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Section: Discussionsupporting

confidence: 82%

Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients

et al. 2004

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“…In their study, c-erbB-4 expression was lower in more aggressive breast cancer cell lines. Suo and coworkers [38] found c-erbB-4 expression to be a favourable prognostic factor in nodenegative breast carcinomas. We could not corroborate their results as we did not find any significant association between c-erbB-4 expression and survival in the PA and subsequent breast carcinoma groups.…”

Section: Discussionmentioning

confidence: 98%

Pregnancy and breast cancer: a population-based study

et al. 2003

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The incidence of pregnancy-associated breast cancer, i.e. during pregnancy and lactation, and of pregnancy subsequent to a breast-cancer diagnosis will increase as more women choose childbearing at a later age. Few larger series are published on pregnancy-associated breast cancer. In a population-based study, we evaluated the outcome and prognostic factors in 173 breast-cancer patients. One hundred and twenty-two patients had pregnancy-associated breast cancer (20 coincident with pregnancy and 102 during lactation) and 51 patients had pregnancy subsequent to breast cancer. The median follow-up time was 151 months. Histopathological parameters and immunoreactivity for oestrogen and progesterone receptors c-erbB-2 and c-erbB-4 were studied. All three groups had tumours with high histological grade, low frequency of hormone receptors and high expression of c-erbB-2. The pregnancy and lactation groups were near identical with regard to all histopathological parameters and outcome. In the two pregnancy-associated breast-cancer groups, tumours were significantly larger, with more extensive lymph-node involvement. For node-negative tumours the respective 5- and 10-year survival rates were 62% and 50% in the pregnancy group and 60% and 50% in the lactation group. For node-positive tumours, respective 5- and 10-year survival rates were 50% and 34% in the pregnancy group and 50% and 33% in the lactation group. In the subsequent group, overall survival was high in both node-negative and -positive groups, with 5- and 10-year survival rates of 80% and 73% and 86% and 76%, respectively. Tumour size, lymph-node status, histological grade, progesterone receptor, oestrogen receptor and c-erbB-2 were significant prognostic factors in the pregnancy-associated breast-cancer patients.

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“…HER-4 overexpression was observed to have an antagonistic effect on the worse outcomes in patients with HER-2 overexpression. Suo et al 32 also described T1GFR family expression in a separate cohort of 107 patients with invasive breast carcinoma treated in China. In this Chinese cohort, HER-2 overexpression was weakly associated with poor patient prognosis and HER-4 overexpression was associated with a good prognosis, but only in the absence of lymph node disease.…”

Section: Discussionmentioning

confidence: 99%

Coexpression of the type 1 growth factor receptor family members HER‐1, HER‐2, and HER‐3 has a synergistic negative prognostic effect on breast carcinoma survival

Wiseman¹,

Makretsov²,

Nielsen³

et al. 2005

Cancer

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BACKGROUNDThe clinical significance of coexpression of type 1 growth factor receptor (T1GFR) family members remains largely unknown. The objective of the current study was to determine the frequency and the possible prognostic effect of coexpression of HER‐1, HER‐2, HER‐3, and HER‐4 by breast carcinoma.METHODSTissue microarrays were constructed using clinically annotated formalin‐fixed, paraffin‐embedded tumor samples from 242 patients with invasive breast carcinomas with a median 15‐year follow‐up. The levels of TIGFR family members (HER‐1–HER‐4) were measured by immunohistochemistry. K‐means clustering algorithm, as well as univariate (Kaplan–Meier, log‐rank test) and multivariate (Cox regression) survival analyses were applied to the data set.RESULTSUsing univariate analysis, expression of HER‐1, HER‐2, and HER‐3, but not HER‐4, was significantly associated with decreased patient disease‐specific survival (P < 0.05). Kaplan–Meier survival analysis showed that coexpression of ≥ 2 of HER‐1, HER‐2, and HER‐3 in any combination was associated with reduced patient disease‐specific survival compared with single marker expression or no expression (35% vs. 65% vs. 78% 10‐year survival rates, P = 0.001). Using multivariate analysis, expression of ≥ 2 of HER‐1, HER‐2, and HER‐3 was independent of lymph node status and tumor size.CONCLUSIONSIn a cohort of patients with breast carcinoma, the authors observed T1GFR family member coexpression (HER‐1, HER‐2, and HER‐3) to have a negative synergistic effect on patient outcome, independent of tumor size or lymph node status. Thus, coexpression of T1GFR family members identified a subset of patients with a poor disease prognosis who may potentially benefit from therapy simultaneously targeting several T1GFR family members. Cancer 2005. © 2005 American Cancer Society.

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Type 1 Protein Tyrosine Kinases in Chinese Breast Carcinomas

Cited by 12 publications

References 52 publications

Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients

Expression of HER3, HER4 and their ligand heregulin-4 is associated with better survival in bladder cancer patients

Pregnancy and breast cancer: a population-based study

Coexpression of the type 1 growth factor receptor family members HER‐1, HER‐2, and HER‐3 has a synergistic negative prognostic effect on breast carcinoma survival

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