title: Higher expression levels of 14-3-3sigma in ductal carcinoma in situ of the breast predict poorer outcome.
abstract: The protein 14-3-3sigma 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 14-3-3sigma in breast cancer and specifically consider whether expression in ductal carcinoma in situ (DCIS) lesions is predictive of disease outcome. We examined 14-3-3sigma 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 14-3-3sigma expression with clinico-pathological parameters and patient outcome. We observed a statistically significant increase in 14-3-3sigma protein expression in ductal hyperplasia, DCIS, and invasive ductal carcinoma (IDC) as compared normal glandular epithelium. In IDC, lower expression of 14-3-3sigma tended to predicted poorer survival time while in DCIS lesions, there was a stronger correlation between relatively higher levels of 14-3-3sigma predicting shorter survival time. Further, of patients who had concurrent DCIS and IDC lesions, those that exhibited a decrease of 14-3-3sigma expression from DCIS to IDC had significantly shorter survival time. Our findings indicate that 14-3-3sigma expression may be a useful prognostic indicator for survival in patients with breast cancer with an elevated 14-3-3sigma in earlier disease predicting a less favorable disease outcome. To our knowledge this is the first published study associating 14-3-3sigma protein expression with breast cancer survival.
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1747, USA.
authors.forename: Nam K
authors.initials: NK
authors.lastname: Yoon
authors.forename: David B
authors.initials: DB
authors.lastname: Seligson
authors.forename: David
authors.initials: D
authors.lastname: Chia
authors.forename: Yahya
authors.initials: Y
authors.lastname: Elshimali
authors.forename: Giri
authors.initials: G
authors.lastname: Sulur
authors.forename: Ai
authors.initials: A
authors.lastname: Li
authors.forename: Steve
authors.initials: S
authors.lastname: Horvath
authors.forename: Erin
authors.initials: E
authors.lastname: Maresh
authors.forename: Vei
authors.initials: V
authors.lastname: Mah
authors.forename: Shikha
authors.initials: S
authors.lastname: Bose
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bonavida
authors.forename: Lee
authors.initials: L
authors.lastname: Goodglick
mesh_terms: D048948:14-3-3 Proteins; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics / Q000473:pathology; D005092:Exonucleases / Q000096:biosynthesis* / Q000235:genetics; D005095:Exoribonucleases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human