Determination of HER2 phosphorylation at tyrosine 1221/1222 improves prediction of poor survival for breast cancer patients with hormone receptor-positive tumors

Frogne, Thomas; Lænkholm, Anne‐Vibeke; Lyng, Maria Bibi; Henriksen, Katrine L; Lykkesfeldt, Annè E.

doi:10.1186/bcr2230

Cited by 72 publications

(81 citation statements)

References 49 publications

(78 reference statements)

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“…However, the phosphorylated tyrosine 1248 of Her-2 was associated with BCR, suggesting that IHC evaluation of the phosphorylated form is better than the standard Her-2 test, which is not clinically used for prostate cancer patients because of a lack of reliability and association with outcome. Interestingly, similar results have been found in breast cancer tissue (Thor et al, 2000;Cicenas et al, 2006;Frogne et al, 2009) when staining of tyrosine 1221/1222 was compared with that of total Her-2. Further studies in larger cohorts would be necessary to validate this initial observation and determine the validity of phospho-Her-2 staining for clinical use in prostate cancer.…”

Section: Discussionsupporting

confidence: 80%

Hierarchical clustering of immunohistochemical analysis of the activated ErbB/PI3K/Akt/NF-κB signalling pathway and prognostic significance in prostate cancer

et al. 2010

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BACKGROUND: The PI3K/Akt signalling pathway, induced by epidermal growth factor receptor (EGFR) and Her-2, is involved in the constitutive activation of NF-kB in prostate cancer cell lines. In this study, we extended the in vitro observation using an ex vivo model of prostate cancer tissues and assessed the prognostic significance of the PI3K/Ak/NF-kB signalling determinants. METHODS: We analysed a prostate cancer tissue microarray of 63 patients for the expression of total and activated EGFR, Her-2 receptors and the signalling molecules PTEN, phospho-PTEN, Akt, phospho-Akt and the NF-kB subunit p65. Data were analysed using Spearman's rho test, Kaplan -Meier curves and multivariate Cox regression analysis. In addition, a non-supervised hierarchical clustering analysis was applied to stratify patients according to prognostic groups in terms of risk of recurrence. RESULTS: The concomitant overexpression of activated EGFR and Her-2 was correlated with the nuclear expression of NF-kB. EGFR, phospho-EGFR, phospho-Her-2, ErbB3 and nuclear NF-kB were associated with the overall biochemical recurrence (BCR) of patients. The non-supervised hierarchical clustering analysis resulted in the separation of patients into five groups according to BCR. CONCLUSIONS: These results validate the previous in vitro data on ErbB involvement in NF-kB activation and shows evidence for a significant role of ErbB/PI3K/Akt/NF-kB signalling in the progression of prostate cancer.

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Section: Discussionsupporting

confidence: 80%

Hierarchical clustering of immunohistochemical analysis of the activated ErbB/PI3K/Akt/NF-κB signalling pathway and prognostic significance in prostate cancer

et al. 2010

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“…We speculate that in these cancers low levels of highly active HER2 proteins may impact on prognosis. These findings are supported by previous observations of Frogne et al [26]; however, the low percentage of pHER2?ve/HER2-ve (15.2 %) cases observed suggests that further validation is required. Nonetheless the potential impact of activation of low levels of HER2 protein on response to a number of therapies is intriguing and might, with extreme caution, be suggested as potential mechanism to explain a number of effects including the observation that some HER2 ''negative'' cases respond to anti-HER2 directed therapies [27].…”

Section: Discussionsupporting

confidence: 91%

Expression of activated type I receptor tyrosine kinases in early breast cancer

Spears

Pederson

Lyttle

et al. 2012

Breast Cancer Res Treat

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Overexpression of EGFR, HER2 and HER3 are known to be associated with poor outcome in breast cancer. Few studies have examined the clinical impact of activation of these proteins. In the present study, we evaluated EGFR, HER2 and HER3 and the activated (phosphorylated) forms of these proteins in patients with early breast cancer. EGFR, HER2, HER3, pEGFR, pHER2 and pHER3 expression was determined by immunohistochemical analysis of tissue microarrays constructed from tumours within the Edinburgh Breast Conservation Series (BCS). The BCS represents a fully-documented consecutive cohort of 1,812 patients treated by breast conservation surgery in a single institution. Our results demonstrate overexpression of HER2 and pHER2 to be associated with a significant reduction in overall survival (OS) (HR: 1.66, 95 % CI 1.22-2.26, p = 0.001 and HR: 1.57, 95 % CI 1.22-2.03, p = 0.001, respectively) and distant relapse-free survival (DRFS) (HR: 1.63, 95 % CI 1.23-2.18, p = 0.001 and HR: 1.55, 95 % CI 1.23-1.97, p = 0.0002, respectively). Paradoxically, expression of pEGFR was associated with a significantly improved OS (HR: 0.67 95 % CI 0.50-0.91, p = 0.01) and DRFS (HR: 0.73, 95 % CI 0.56-0.96, p = 0.025). Expression of activated EGFR/HER2 provides additional information on ER positive breast cancer patients and suggests alternative treatment for those in this subgroup.

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“…We have investigated AKT, phospho-AKT (pAKT) and Stathmin. The role of phospho-AKT staining as a prognostic marker has been explored in other cancer types, such as ovarian 195,196 , breast 197,198 and cervical cancer 199 , with conflicting results: only two of these studies, those of Guo and co-workers and Wu and collaborators, showed an independent value in relation to survival.…”

Section: Immunomarkers Predicting Survivalmentioning

confidence: 99%

Improved survival related to changes in endometrial cancer treatment, a 30-year population based perspective

Trovik

Mauland

Werner

et al. 2012

Gynecologic Oncology

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Determination of HER2 phosphorylation at tyrosine 1221/1222 improves prediction of poor survival for breast cancer patients with hormone receptor-positive tumors

Cited by 72 publications

References 49 publications

Hierarchical clustering of immunohistochemical analysis of the activated ErbB/PI3K/Akt/NF-κB signalling pathway and prognostic significance in prostate cancer

Hierarchical clustering of immunohistochemical analysis of the activated ErbB/PI3K/Akt/NF-κB signalling pathway and prognostic significance in prostate cancer

Expression of activated type I receptor tyrosine kinases in early breast cancer

Improved survival related to changes in endometrial cancer treatment, a 30-year population based perspective

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