A shift from nuclear to cytoplasmic breast cancer metastasis suppressor 1 expression is associated with highly proliferative estrogen receptor-negative breast cancers.
OBJECTIVE
To determine breast cancer metastasis suppressor 1 (BRMS1) expression in breast cancers and the efficacy of BRMS1 as a prognostic indicator, BRMS1 expression was assessed in two sets of breast cancer tissues.


METHODS
Epithelial cells from 36 frozen samples of breast cancers and corresponding normal breast were collected by laser capture microdissection and assessed for BRMS1 by quantitative RT-PCR and immunohistochemistry. BRMS1 was also evaluated by immunohistochemistry in a tissue microarray of 209 breast cancers and correlated with indicators of prognosis [estrogen receptor (ER), progesterone receptor (PR), ErbB2, p53, p27(Kip1), Bcl2 and Ki-67].


RESULTS
BRMS1 mRNA and protein were higher in 94 and 81%, respectively, of breast cancers than in corresponding normal epithelium. BRMS1 localization was predominantly nuclear, but 60-70% of cancers also exhibited cytoplasmic immunostaining. Breast cancers with lower nuclear than cytoplasmic BRMS1 (nuclear score - cytoplasmic score < or =0; 11% of cancers) had lower ER, lower PR and higher Ki-67 expression. There was also a trend toward poorer overall survival in this group of cancers, but this was only of borderline significance (p = 0.073). In Cox proportional hazards models, loss of nuclear BRMS1 was not a significant predictor of overall survival.


CONCLUSIONS
Loss of nuclear BRMS1 was associated with ER-negative cancers and a high rate of proliferation, but was not an independent indicator of prognosis.
Frolova
Natalya
N
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Edmonds
Mick D
MD
Bodenstine
Thomas M
TM
Seitz
Robert
R
Johnson
Martin R
MR
Feng
Rui
R
Welch
Danny R
DR
Frost
Andra R
AR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007834:Lasers; D042282:Microdissection; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
C410024:BRMS1 protein, human; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D012097:Repressor Proteins