Abstract 2651: Nestin expression in tumor cells is associated with the basal-like phenotype and aggressive features in breast cancer.

Abstract

Abstract Background: Nestin, neuroepithelial stem cell protein, is an intermediate filament protein originally described as a neuronal stem cell/progenitor marker during central nervous system development. Nestin is also expressed in immature or progenitor cells in non-neural tissues, including the basal/myoepithelial layer of the mammary gland and immature blood vessels. Recently, nestin positivity has been reported in different cancer types, and on this background we wanted to evaluate nestin positivity in breast cancer. Materials and methods: Immunohistochemical staining of nestin was done on tissue microarray slides from two independent series of breast cancer. Series 1 was a nested case-control study of interval and screening detected breast cancer based on the Norwegian Mammography Screening Program in Hordaland County during 1996-2001, giving a series of 190 patients with invasive breast cancer. Series 2 included 192 cases of invasive breast carcinoma from 1990-2002 identified in the Kampala Cancer Registry, and at the Department of Pathology, Makerere University College of Health Sciences (MakCHS), Kampala, Uganda. Evaluation of staining was done using staining index, where the staining index (values 0-9) was obtained as a product of staining intensity (0-3) and proportion of immunopositive cells (<10%, 1; 10-50%, 2; >50%, 3). A staining index above 0 was regarded as positivity for nestin. Results: In both series, nestin positivity in tumor cells was significantly associated with higher histologic grade; grade 1-2 vs. grade 3, (p<0.0005), negativity for estrogen receptor (p<0.0005) and progesterone receptor (p=0.001 in series 1 and p<0.0005 in series 2), high tumor cell proliferation by Ki-67 (p<0.0005 and p=0.005 in series 1 and 2, respectively), positivity for p53 (p=0.001 in series 1 and p=0.010 in series 2) and increased activation of angiogenesis estimated by vascular proliferation index (VPI)(p=0.035 in series 1 and p=0.001 in series 2). Concerning basal cell markers, nestin positivity in tumor cells was significantly associated with cytokeratin 5/6 and p-cadherin, with p-values <0.0005 in both series. Further, strong associations were seen with the triple negative phenotype (p<0.0005) and with five immunohistochemical profiles for the basal-like phenotype (1-5), with odds ratios from 7.1-18.3 and 10.7-18.1 in series 1 and 2, respectively. Conclusion: In these two series of breast cancer, nestin expression in tumor cells was significantly associated with features of aggressive breast cancer disease such as higher histologic grade, negativity for estrogen and progesterone receptors and high tumor cell proliferation by Ki-67. Further, nestin positivity was significantly associated with basal cell markers, the triple negative phenotype and the basal-like phenotype. Citation Format: Kristi Krüger, Hawa Nalwoga, Karin Collett, Jarle B. Arnes, Turid Aas, Lars A. Akslen. Nestin expression in tumor cells is associated with the basal-like phenotype and aggressive features in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2651. doi:10.1158/1538-7445.AM2013-2651