Abstract 3206: Increased expression levels of WAVE3 are associated with breast cancer progression and metastasis

Abstract

Abstract Cancer metastasis is a complex process, usually requiring cancer cells to escape from the primary site, survive in the blood/lymph system and then to colonize a distant site. We have shown that the expression levels of WAVE3 are significantly correlated with advanced stages of breast cancer (BC). Our published studies have now established a function for WAVE3 as a metastasis promoter gene in BC. We, therefore, used immunohistochemistry to test the prognostic value of WAVE3 in the progression and metastasis of BC. We analyzed the expression levels of WAVE3 in 61 patients with Scarff-Bloom-Richardson (SBR) grade 1 and ER+ tumors (SBR1/ER+), which were matched to 61 patients with SBR grade 3 and ER- tumors (SBR3/ER-). The product of staining intensity (0-3) and percentage of stained cells (0-100) was used to derive a WAVE3 score (0-300). In all 122 patients, median WAVE3 score increased with tumor size (p=0.009), (+) lymph node status (p=0.03), and stage (p=0.012). Distant recurrence (DR) and BC specific survival could only be assessed in the SBR3/ER- group, where median WAVE3 score was elevated with DR and BC specific mortality. A WAVE3 score ≥ 212 was associated with distant recurrence and BC specific mortality in Kaplan Meier analysis (p=0.03), as well as with an increased risk for BC specific mortality (p=0.004). From the immunohistochemistry analysis we concluded that WAVE3 is associated with tumor size, stage, DR and BC specific mortality in the high risk SBR3/ER- group. WAVE3 expression may, therefore, contribute to adverse outcome in high risk breast cancer patients. On the other hand, WAVE3 is expressed at very low levels in the hematopoietic cells, but its expression levels are increased in the circulating tumor cells (CTC) that result from early tumor cell dissemination even in patients with small tumors. We are therefore using this WAVE3-specific characteristic to evaluate the prognostic value of WAVE3 expression levels in CTCs in women with operable breast cancer, since the presence of CTCs after adjuvant chemotherapy has been associated with a poor clinical outcome even in patients with early-stage breast cancer. To do this we used quantitative real-time RT-PCR to assess the expression levels of WAVE3 in the blood of 200 breast cancer patients, representative of different stages and pathology of the disease, after they have completed surgery and chemotherapy. The expression data will be correlated with the clinicopathiological parameters and disease outcome in a similar manner as the immunostaining data, and the results will be presented during the meeting. This study is aimed to define the role of WAVE3 in the progression and metastasis of breast cancer and to provide a fundamental and sound scientific basis upon which the role of WAVE3 can be evaluated in breast cancer and utilized as a prognostic indicator in the clinic setting, specifically predicting women at increased risk of distant metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3206. doi:10.1158/1538-7445.AM2011-3206