Cytoplasmic p21WAF1/CIP1 expression is correlated with HER-2/neu in breast cancer and is an independent predictor of prognosis
| العنوان: | Cytoplasmic p21WAF1/CIP1 expression is correlated with HER-2/neu in breast cancer and is an independent predictor of prognosis |
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| المؤلفون: | Mike Bradburn, Russell Leek, Adrian L. Harris, Chris J. Norbury, Zoe Winters |
| المصدر: | Scopus-Elsevier Breast Cancer Research |
| بيانات النشر: | BioMed Central, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Adult, Cyclin-Dependent Kinase Inhibitor p21, Oncology, Cytoplasm, medicine.medical_specialty, Receptor, ErbB-2, Breast Neoplasms, CDK inhibitor, Breast cancer, Tumours, Predictive Value of Tests, Surgical oncology, Cyclins, Internal medicine, medicine, Carcinoma, Humans, Survival analysis, phosphatidylinositol-3 kinase/protein kinase B, Aged, Aged, 80 and over, Medicine(all), business.industry, Kinase, Carcinoma, Ductal, Breast, Cancer, Middle Aged, Prognosis, medicine.disease, Immunohistochemistry, Survival Analysis, Cancer research, business, prognostic markers, Research Article |
| الوصف: | Background\ud HER-2 (c-erbB2/Neu) predicts the prognosis of and may influence treatment responses in breast cancer. HER-2 activity induces the cytoplasmic location of p21WAFI/CIPI in cell culture, accompanied by resistance to apoptosis. p21WAFI/CIPI is a cyclin-dependent kinase inhibitor activated by p53 to produce cell cycle arrest in association with nuclear localisation of p21WAFI/CIPI . We previously showed that higher levels of cytoplasmic p21WAFI/CIPI in breast cancers predicted reduced survival at 5 years. The present study examined HER-2 and p21WAFI/CIPI expression in a series of breast cancers with up to 9 years of follow-up, to evaluate whether in vitro findings were related to clinical data and the effect on outcome.\ud \ud Methods\ud The CB11 anti-HER2 monoclonal antibody and the DAKO Envision Plus system were used to evaluate HER-2 expression in 73 patients. p21WAFI/CIPI staining was performed as described previously using the mouse monoclonal antibody Ab-1 (Calbiochem, Cambridge, MA, USA).\ud \ud Results\ud HER-2 was evaluable in 67 patients and was expressed in 19% of cases, predicting reduced overall survival (P = 0.02) and reduced relapse-free survival (P = 0.004; Cox regression model). HER-2-positive tumours showed proportionately higher cytoplasmic p21WAFI/CIPI staining using an intensity distribution score (median, 95) compared with HER-2-negative cancers (median, 47) (P = 0.005). There was a much weaker association between nuclear p21WAFI/CIPI and HER-2 expression (P = 0.05), suggesting an inverse relationship between nuclear p21WAF1/CIP1 and HER-2.\ud \ud Conclusion\ud This study highlights a new pathway by which HER-2 may modify cancer behaviour. HER-2 as a predictor of poor prognosis may partly relate to its ability to influence the relocalisation of p21WAFI/CIPI from the nucleus to the cytoplasm, resulting in a loss of p21WAFI/CIPI tumour suppressor functions. Cytoplasmic p21WAFI/CIPI may be a surrogate marker of functional HER-2 in vivo. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1465-5411 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::94e0f42fb5ab9eeb5c1373e8a9891b99Test https://ora.ox.ac.uk/objects/uuid:81e09c43-d859-4dbe-aa31-b1d1ecd1065eTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....94e0f42fb5ab9eeb5c1373e8a9891b99 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14655411 |
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