JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Transforming acidic coiled-coil-containing protein 2 (TACC2) in human breast cancer, expression pattern and clinical/prognostic relevance.

TACC2 is a member of the transforming acidic coiled-coil-containing protein family and is associated with the centrosome-spindle apparatus during cell cycling. The TACC2 gene is expressed in various splice forms predominantly in postmitotic tissues, including heart, muscle, kidney, and brain. Recent work has shown that members of this family, including TACC2, may be involved in the progression of certain solid tumours. The aim of the current study was to identify the role of TACC2 in breast cancer and to establish if a prognostic relevance existed. Fresh frozen primary human breast cancer tissues (n=127) and non-neoplastic mammary tissues (n=33) were used. The distribution and location of TACC2 was assessed using immunohistochemical staining (IHC). The transcript levels of TACC2 were determined using quantitative real-time PCR. The results were analyzed against the clinical, pathological and follow-up (10 years) data. Statistical analysis was by two-sample t-test and Kaplan-Meier method. TACC2 protein staining was seen in both normal epithelial cells and cancer cells in mammary tissues. Quantitative analysis of the TACC2 transcript revealed a higher level of expression in tumours compared with normal tissues. TACC2 expression was significantly increased in higher grade tumours compared to that in lower grade tumours (grade 3 vs. grade 1, p=0.046). Using the Nottingham Prognostic Index (NPI), TACC2 transcript was significantly higher in tumours from patients with a moderate prognosis than from those with a good prognosis (p=0.045). The expression in samples from patients with poor clinical outcome (with metastasis, recurrence and breast cancer related death) was higher than that in those from patients who remained disease free. This was reflected by a shorter disease-free survival for patients with high TACC2 (107 (95% confidence interval: 91-122.8) months compared with 137 (125-150.6) months for patients with low TACC2 transcripts (p=0.019). This study shows that increased expression of TACC2 correlates with poor prognosis in patients with breast cancer. This suggests that TACC2 may mediate an oncogenic effect on breast cancer cells and indicates that TACC2 may be a potential therapeutic target.

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