Distribution and significance of 14-3-3sigma, a novel myoepithelial marker, in normal, benign, and malignant breast tissue.
14-3-3sigma is a candidate tumour suppressor gene transactivated by p53 in response to DNA damage. In gene expression analysis of normal luminal and myoepithelial cells, 14-3-3sigma was preferentially expressed by myoepithelial cells. This study has analysed the immunohistochemical distribution and subcellular localization of 14-3-3sigma in normal breast tissue and in a large series of benign and malignant breast lesions on whole tissue sections and by tissue microarray. Immunohistochemistry demonstrated that 14-3-3sigma was consistently expressed in the cytoplasmic compartment and occasionally in the nuclei of myoepithelial cells arranged as a continuous layer around normal ducts and lobular units, whereas luminal epithelial, stromal, endothelial, pericytic, lipomatous, and neural cells showed no staining. Myoepithelial cells of benign proliferations and pre-invasive lesions were consistently positive for 14-3-3sigma. Strong expression of 14-3-3sigma was evident in one case of ductal carcinoma in situ (5.5%) and in 105/554 invasive cancers (18.9%). Survival data were available for 452 patients with invasive breast carcinoma. 14-3-3sigma cytoplasmic subcellular localization was a statistically significant prognostic factor for the whole series of invasive carcinomas, as well as for those positive for oestrogen (ER) or progesterone receptors (PR). This analysis demonstrates the utility of 14-3-3sigma as a new adjunct antibody for characterization of myoepithelial cells and myoepithelial lesions and it may be a novel prognostic factor for breast cancer patients.
The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
Peter T
PT
Simpson
Theodora
T
Gale
Jorge S
JS
Reis-Filho
Chris
C
Jones
Suzanne
S
Parry
Dawn
D
Steele
Antonio
A
Cossu
Mario
M
Budroni
Giuseppe
G
Palmieri
Sunil R
SR
Lakhani
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor / Q000032:analysis*; D001941:Breast Diseases / Q000378:metabolism; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality; D044584:Carcinoma, Ductal / Q000737:chemistry; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry; D018275:Carcinoma, Lobular; D002467:Cell Nucleus / Q000737:chemistry; D016009:Chi-Square Distribution; D003593:Cytoplasm / Q000737:chemistry; D005092:Exonucleases / Q000032:analysis*; D005095:Exoribonucleases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D009208:Myoepithelioma / Q000737:chemistry* / Q000401:mortality; D009363:Neoplasm Proteins / Q000032:analysis*; D016016:Proportional Hazards Models; D016019:Survival Analysis
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human