P1-02-10: Vimentin Expression; as a Prognostic Factor and a Possible Molecular Target of Triple Negative Breast Cancer.
Authors: Yamashita N , Tokunaga E , Kitao H , Hisamatsu Y , Akiyoshi S , Saeki H , Oki E , Ohga T , Kakeji Y , Maehara Y 
Published: June 2012

BACKGROUND: Triple negative breast cancer (TNBC), characterized by absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), is typically associated with aggressive tumor phenotype and poor prognosis. TNBC is also considered highly heterogeneous disease. Since TNBC lacks efficient therapeutic target, it is generally treated with nonspecific cytotoxic agents. A better understanding of molecular and histopathological features of TNBC is of great importance, in order to develop a new therapeutic strategy and to improve the prognosis of TNBC. TNBC has many similarities with basal-like breast cancer (BLBC), and is also associated with stemness and BRCAness. In addition, recent studies suggest links between TNBC and epithelial-mesenchymal transition (EMT). To identify prognostic biomarkers and novel therapeutic targets, we investigated the expression of the factors associated with EMT in TNBC.

MATERIALS and METHODS: Sporadic invasive breast cancer specimens were obtained from 659 Japanese patients who underwent surgery in our department between 1994 and 2010, and 90(14%) cases were diagnosed as TNBC. The E-cadherin and vimentin mRNA expression was evaluated by quantitative RT-PCR. The E-cadherin, vimentin, CK5/6 and epidermal growth factor receptor(EGFR) protein expression was assessed by immunohistochemistry. In this study, we defined TNBC with positive expression of CK5/6 and/or EGFR as BLBC, and TNBC with low expression of E-cadherin and positive expression of vimentin as EMT-type.

RESULTS: Compared with non-TNBC cases, E-cadherin mRNA expression was significantly lower in TNBC cases (p=0.0012). Immunohistochemically, E-cadherin expression was significantly lower (p=0.0001) and vimentin expression was significantly higher (p=0.0049) in TNBC cases. Vimentin expression was associated with younger age (&lt;50 years old, p=0.021), high nuclear grade (p=0.017) and high Ki67 expression (p&lt;.001) in TNBC. Among the patients with TNBC, vimentin expression was significantly associated with poor prognosis, in terms of disease free survival (p=0.0059) and overall survival (p=0.013). Multivariate analysis showed that vimentin expression was an independent prognostic factor for both disease free survival (p=0.017) and overall survival (p=0.012). Among TNBC cases, 52(63%) cases were BLBCs and 15(18%) cases were EMT-type. Among BLBC patients, vimentin expression was also associated with significantly shorter disease free survival (p=0.0085) and overall survival (p=0.0057). The patients with both BLBC and EMT-type features showed especially poor prognosis(P=0.05). CONCLUSION: These findings suggest that elevated expression of vimentin attributes to the aggressive phenotype in TNBC patients. Vimentin expression might be useful as a molecular marker for prognosis of TNBC, and vimentin may represent a novel therapeutic target of TNBC.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-02-10.