Thioredoxin interacting protein (TXNIP) is an independent risk stratifier for breast ductal carcinoma in situ
Current clinicopathological parameters are useful predictors of breast ductal carcinoma in situ behaviour, but they are insufficient to define high risk patients for disease progression precisely. Thioredoxin interacting protein (TXNIP) is a key player of oxidative stress. This study aims to evaluat...
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | https://eprints.nottingham.ac.uk/52002/ |
| _version_ | 1848798624161464320 |
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| author | Miligy, Islam Gorringe, Kylie L. Toss, Michael S. Al-Kawaz, Abdubaqi Simpson, Peter Diez-Rogriguez, Maria Nolan, Christopher C. Ellis, Ian O. Green, Andrew R. Rakha, Emad |
| author_facet | Miligy, Islam Gorringe, Kylie L. Toss, Michael S. Al-Kawaz, Abdubaqi Simpson, Peter Diez-Rogriguez, Maria Nolan, Christopher C. Ellis, Ian O. Green, Andrew R. Rakha, Emad |
| author_sort | Miligy, Islam |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Current clinicopathological parameters are useful predictors of breast ductal carcinoma in situ behaviour, but they are insufficient to define high risk patients for disease progression precisely. Thioredoxin interacting protein (TXNIP) is a key player of oxidative stress. This study aims to evaluate the role of TXNIP as a predictor of ductal carcinoma in situ progression. Tissue microarrays from 776 pure ductal carcinoma in situ and 239 mixed ductal carcinoma in situ and invasive tumors were constructed. All patients were treated at a single institution with a long-term follow-up and TXNIP expression was assessed using immunohistochemistry. TXNIP expression was investigated in terms of associations with clinicopathological and molecular features and patient outcome. Loss/reduced cytoplasmic expression of TXNIP was associated with features of aggressiveness including high nuclear grade (p=1.6x10-5), presence of comedo necrosis (p=0.001) and oestrogen receptor negative (ER-)/HER2- ductal carcinoma in situ (p=4.6x10-5). Univariate analysis showed an inverse association between TXNIP expression and outcome in terms of shorter local recurrence free survival (p=0.009). Multivariable analyses showed that independent predictors of ductal carcinoma in situ recurrence were low TXNIP expression (p=0.005, HR=0.51 and 95%CI: 0.32-0.81), larger ductal carcinoma in situ size and high nuclear grade. TXNIP functions as a tumor suppressor gene with loss of its expression associated with ductal carcinoma in situ recurrence. TXNIP can be used as a potentially useful marker in prognostic stratification of ductal carcinoma in situ for management decisions. |
| first_indexed | 2025-11-14T20:22:44Z |
| format | Article |
| id | nottingham-52002 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:22:44Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-520022020-05-04T19:43:06Z https://eprints.nottingham.ac.uk/52002/ Thioredoxin interacting protein (TXNIP) is an independent risk stratifier for breast ductal carcinoma in situ Miligy, Islam Gorringe, Kylie L. Toss, Michael S. Al-Kawaz, Abdubaqi Simpson, Peter Diez-Rogriguez, Maria Nolan, Christopher C. Ellis, Ian O. Green, Andrew R. Rakha, Emad Current clinicopathological parameters are useful predictors of breast ductal carcinoma in situ behaviour, but they are insufficient to define high risk patients for disease progression precisely. Thioredoxin interacting protein (TXNIP) is a key player of oxidative stress. This study aims to evaluate the role of TXNIP as a predictor of ductal carcinoma in situ progression. Tissue microarrays from 776 pure ductal carcinoma in situ and 239 mixed ductal carcinoma in situ and invasive tumors were constructed. All patients were treated at a single institution with a long-term follow-up and TXNIP expression was assessed using immunohistochemistry. TXNIP expression was investigated in terms of associations with clinicopathological and molecular features and patient outcome. Loss/reduced cytoplasmic expression of TXNIP was associated with features of aggressiveness including high nuclear grade (p=1.6x10-5), presence of comedo necrosis (p=0.001) and oestrogen receptor negative (ER-)/HER2- ductal carcinoma in situ (p=4.6x10-5). Univariate analysis showed an inverse association between TXNIP expression and outcome in terms of shorter local recurrence free survival (p=0.009). Multivariable analyses showed that independent predictors of ductal carcinoma in situ recurrence were low TXNIP expression (p=0.005, HR=0.51 and 95%CI: 0.32-0.81), larger ductal carcinoma in situ size and high nuclear grade. TXNIP functions as a tumor suppressor gene with loss of its expression associated with ductal carcinoma in situ recurrence. TXNIP can be used as a potentially useful marker in prognostic stratification of ductal carcinoma in situ for management decisions. Nature Publishing Group 2018-06-28 Article PeerReviewed Miligy, Islam, Gorringe, Kylie L., Toss, Michael S., Al-Kawaz, Abdubaqi, Simpson, Peter, Diez-Rogriguez, Maria, Nolan, Christopher C., Ellis, Ian O., Green, Andrew R. and Rakha, Emad (2018) Thioredoxin interacting protein (TXNIP) is an independent risk stratifier for breast ductal carcinoma in situ. Modern Pathology . ISSN 1530-0285 Suctal carcinoma in situ; Predictor; Outcome; Progression; TXNIP Immunohistochemistry https://www.nature.com/articles/s41379-018-0086-7 doi:10.1038/s41379-018-0086-7 doi:10.1038/s41379-018-0086-7 |
| spellingShingle | Suctal carcinoma in situ; Predictor; Outcome; Progression; TXNIP Immunohistochemistry Miligy, Islam Gorringe, Kylie L. Toss, Michael S. Al-Kawaz, Abdubaqi Simpson, Peter Diez-Rogriguez, Maria Nolan, Christopher C. Ellis, Ian O. Green, Andrew R. Rakha, Emad Thioredoxin interacting protein (TXNIP) is an independent risk stratifier for breast ductal carcinoma in situ |
| title | Thioredoxin interacting protein (TXNIP) is an independent risk stratifier for breast ductal carcinoma in situ |
| title_full | Thioredoxin interacting protein (TXNIP) is an independent risk stratifier for breast ductal carcinoma in situ |
| title_fullStr | Thioredoxin interacting protein (TXNIP) is an independent risk stratifier for breast ductal carcinoma in situ |
| title_full_unstemmed | Thioredoxin interacting protein (TXNIP) is an independent risk stratifier for breast ductal carcinoma in situ |
| title_short | Thioredoxin interacting protein (TXNIP) is an independent risk stratifier for breast ductal carcinoma in situ |
| title_sort | thioredoxin interacting protein (txnip) is an independent risk stratifier for breast ductal carcinoma in situ |
| topic | Suctal carcinoma in situ; Predictor; Outcome; Progression; TXNIP Immunohistochemistry |
| url | https://eprints.nottingham.ac.uk/52002/ https://eprints.nottingham.ac.uk/52002/ https://eprints.nottingham.ac.uk/52002/ |