Higher expression levels of 14-3-3σ in ductal carcinoma in situ of the breast predict poorer outcome¹

Article type: Research Article

Authors: Yoon, Nam K.^a | Seligson, David B.^{a; b} | Chia, David^{a; b} | Elshimali, Yahya^a | Sulur, Giri^a | Li, Ai^c | Horvath, Steve^{b; c; d} | Maresh, Erin^a | Mah, Vei^a | Bose, Shikha^f | Bonavida, Benjamin^{b; e} | Goodglick, Lee^{a; b; *}

Affiliations: [a] Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA | [b] Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA | [c] Department of Biostatistics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA | [d] Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA | [e] Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA | [f] Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

Correspondence: [*] Corresponding author: Lee Goodglick, Ph.D., Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave; Center for the Health Sciences, Box 951747, Los Angeles, CA, 90095-1747, USA. Tel.: +1 310 825 9134; E-mail: lgoodglick@mednet.ucla.edu.

Note: [1] This work was supported in part by the Early Detection Research Network NCI CA-86366 (LG, DC, and DS) the Jonsson Comprehensive Cancer Center (JCCC) Shared Resource Core Grant at UCLA NIH NCI 2 P30 CA16042-29 (DS).

Abstract: The protein 14-3-3σ is involved in the regulation of cellular processes such as apoptosis, cell cycle progression and proliferation. Disruption of protein expression has been implicated in a number of malignancies. Here we examine the expression pattern of 14-3-3σ in breast cancer and specifically consider whether expression in ductal carcinoma in situ (DCIS) lesions is predictive of disease outcome. We examined 14-3-3σ protein expression and localization using immunohistochemical staining on a high-density tissue microarray consisting of 157 invasive breast cancer patients. Statistical analyses were used to assess the correlation of 14-3-3σ expression with clinico-pathological parameters and patient outcome. We observed a statistically significant increase in 14-3-3σ protein expression in ductal hyperplasia, DCIS, and invasive ductal carcinoma (IDC) as compared normal glandular epithelium. In IDC, lower expression of 14-3-3σ tended to predicted poorer survival time while in DCIS lesions, there was a stronger correlation between relatively higher levels of 14-3-3σ predicting shorter survival time. Further, of patients who had concurrent DCIS and IDC lesions, those that exhibited a decrease of 14-3-3σ expression from DCIS to IDC had significantly shorter survival time. Our findings indicate that 14-3-3σ expression may be a useful prognostic indicator for survival in patients with breast cancer with an elevated 14-3-3σ in earlier disease predicting a less favorable disease outcome. To our knowledge this is the first published study associating 14-3-3σ protein expression with breast cancer survival.

Keywords: Tissue microarray, breast cancer, tumor marker, 14-3-3σ, prognostic marker, DCIS

DOI: 10.3233/CBM-2009-0106

Journal: Cancer Biomarkers, vol. 5, no. 4-5, pp. 215-224, 2009