Abstract 3937: Nestin expression is associated with a basal-like phenotype and poor prognosis in breast cancer

Abstract

Abstract Background: Nestin, neuroepitheilal stem cell protein, is an intermediate filament protein first described in neural stem or progenitor cells, and its expression has been seen in several tissues, including different types of cancer. In breast cancer, Nestin expression has been linked to the triple negative and basal-like phenotypes. We here evaluated Nestin and its association with clinico-pathologic markers and survival in two prospective Norwegian breast cancer cohorts. Materials and methods: Series I includes 546 women (50-69 years) diagnosed with primary invasive breast cancer (403 screen-detected and 143 interval cancers) as part of the prospective and population-based Norwegian Breast Cancer Screening Program (NBCSP) during 1996-2003 (Hordaland county). Series II includes 282 women (50-69 years) with invasive cancers (199 screen-detected and 83 interval cancers) diagnosed as part of the NBCSP during 2004-2009 (Vestfold County). Immunohistochemical staining of Nestin was done on tissue microarrays (TMAs). Expression in tumor cells was graded by a Staining Index (SI) (values 0-9). Results: Nestin positivity, observed in 9% and 13% of the breast cancer cases in Series I and II, was associated with higher histological grade (OR, odds ratio 14.3 and 8.1), high tumor cell proliferation by Ki-67 (OR 11.4 and 9.1), larger tumor diameter (OR 1.8 and 2.4), but not with lymph node status or HER2 status. Further, Nestin positivity was associated with negativity for estrogen (OR 14.9 and 11.9) and progesterone receptor (8.5 and 3.4), the triple negative phenotype (OR 29.1 and 17.4) and basal-like differentiation by positivity for Cytokeratin 5 (OR 9.1 and 8.7) or P-cadherin (OR 7.0 and 8.5). By univariate survival analysis, Nestin positivity was associated with reduced breast cancer specific (p = 0.002 and p = 0.076) and overall survival (p = 0.005 and p = 0.039). When including the standard variables tumor size, histologic grade and lymph node status in a multivariate analysis, Nestin was still significantly associated with reduced breast cancer specific survival in the largest cohort (Series I). Conclusion: We found that Nestin expression in breast cancer is associated with aggressive features, the triple negative phenotype, basal-like differentiation, and reduced breast cancer specific survival. Citation Format: Kristi Krüger, Elisabeth Wik, Tor Audun Klingen, Ying Chen, Turid Aas, Lars A. Akslen. Nestin expression is associated with a basal-like phenotype and poor prognosis in breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3937.