Co-Expression of p16, Ki67 and COX-2 Is Associated with Basal Phenotype in High-Grade Ductal Carcinoma In Situ of the Breast

Perez, Amanda Arantes; Balabram, Débora; Souza, Átila da Silva; Gobbi, Helenice

doi:10.1369/0022155415576540

Cited by 20 publications

(21 citation statements)

References 34 publications

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“…Therefore, it may be hypothesized that COX-2 has potential as a prognostic biomarker for breast cancer. Previous studies have reported that COX-2 was upregulated and associated with tumor invasiveness and clinical outcome in numerous types of human cancer (27)(28)(29)(30). In the present study, a correlation was revealed between high COX-2 expression and poor differentiation status (P<0.05).…”

Section: Discussionsupporting

confidence: 68%

EpCAM and COX-2 expression are positively correlated in human breast cancer

Gao

Sun

et al. 2017

Molecular Medicine Reports

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Upregulation of the epithelial cell adhesion molecule (EpCAM) is involved in tumor progression. Cyclooxygenase (COX)‑2 is the key enzyme catalyzing prostaglandin synthesis and is involved in breast cancer progression and metastasis. However, the prognostic value of EpCAM and its putative correlation with COX‑2 in breast cancer have yet to be elucidated. The aim of the present study was to assess the clinical relevance of the relationship between EpCAM and COX‑2, via examining the putative correlation between EpCAM and COX‑2 expression in various types of human breast cancer. A total of 134 breast cancer tissue samples was examined in the present study. Immunohistochemistry approach was used to detect EpCAM and COX‑2 expression in the tissue microarrays. Spearman's correlation analysis was performed to evaluate the correlation between the protein expression and clinicopathological parameters present in patients with various tumor subtypes, with the aim to potentially establish a relationship between EpCAM/COX‑2 and clinical prognosis. Expression of EpCAM and COX‑2 was revealed to be associated with tumor progression, and poor prognosis in breast cancer. The present findings demonstrated that EpCAM was involved in the regulation of COX‑2 expression, and a positive correlation between the proteins was associated with poor prognosis in patients with breast cancer. The present results suggest that EpCAM and COX‑2 may have potential as prognostic biomarkers in the diagnosis and treatment of patients with breast cancer.

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Section: Discussionsupporting

confidence: 68%

EpCAM and COX-2 expression are positively correlated in human breast cancer

Gao

Sun

et al. 2017

Molecular Medicine Reports

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“…Previous reports showed that p16 is over‐expressed in basal breast carcinoma (Perez et al . ). Although MDA‐MB‐231 is derived from adenocarcinoma, the aggressive phenotype of this type of breast cancer cells can be attenuated by miR‐340 over‐expression followed by p16 decline.…”

Section: Discussionmentioning

confidence: 97%

The effect of miR-340 over-expression on cell-cycle-related genes in triple-negative breast cancer cells

et al. 2016

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Breast cancer is a heterogeneous disease, and among all types, triple-negative breast cancer (TNBC) is characterised by high risk of recurrence. The discovery of microRNAs (miRNA) has opened the door for targeted therapy of TNBC. miR-340 down-regulation and sub-G1-accumulated cells in flowcytometry were observed in metastatic TNBC cells (data in publication), leading us to investigate the potential tumour suppressive role of this miRNA on cell-cycle-related genes. A lentiviral vector containing miR-340 was applied to over-express miR-340 in TNBC cell line, MDA-MB-231. Then, the expression of some cell-cycle-regulating genes including cyclin A2 (cyclin A2), Cyclin-dependent kinases 2 (CDK2), cyclin-dependent kinase inhibitors (P16, P18 and P27), Retinoblastoma (RB) and transcription factors (SMAD 4, SOX2 and SOX17) was investigated using quantitative RT-PCR. The results showed a decline in the expression of SOX2, P16 and P27 after miR-340 over-expression, whereas we observed an increase in the expression of cyclin A2, CDK2, SOX17, P18, SMAD 4 and RB. The over-expression of tumour suppressor genes such as RB and SOX17 and down-regulation of an oncogene such as SOX2 were in accordance to the inhibitory role of miR-340 that causes blockage of breast cancer metastasis which should be further investigated.

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“…The treatment of ductal carcinoma in situ remains a challenge as the clinicopathologic features of the disease do not reliably stratify patients into distinct risk groups to guide treatment decision [23]. For this reason, some studies have attempted to risk stratify ductal carcinoma in situ based on genetic and molecular factors, including Oncotype Dx ® ductal carcinoma in situ score [24][25][26][27][28]. Although ductal Fig.…”

Section: Discussionmentioning

confidence: 99%

Thioredoxin-interacting protein is an independent risk stratifier for breast ductal carcinoma in situ

et al. 2018

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Current clinicopathological parameters are useful predictors of breast ductal carcinoma in situ behavior, 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 = 1.6 × 10), presence of comedo necrosis (p = 0.001), and estrogen receptor negative (ER-)/HER2- ductal carcinoma in situ (p = 4.6 × 10). 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.

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Co-Expression of p16, Ki67 and COX-2 Is Associated with Basal Phenotype in High-Grade Ductal Carcinoma In Situ of the Breast

Cited by 20 publications

References 34 publications

EpCAM and COX-2 expression are positively correlated in human breast cancer

EpCAM and COX-2 expression are positively correlated in human breast cancer

The effect of miR-340 over-expression on cell-cycle-related genes in triple-negative breast cancer cells

Thioredoxin-interacting protein is an independent risk stratifier for breast ductal carcinoma in situ

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