Higher expression levels of 14-3-3sigma in ductal carcinoma in situ of the breast predict poorer outcome.
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.
Yoon
Nam K
NK
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1747, USA.
Seligson
David B
DB
Chia
David
D
Elshimali
Yahya
Y
Sulur
Giri
G
Li
Ai
A
Horvath
Steve
S
Maresh
Erin
E
Mah
Vei
V
Bose
Shikha
S
Bonavida
Benjamin
B
Goodglick
Lee
L
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
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human