Expression of BP1, a novel homeobox gene, correlates with breast cancer progression and invasion.
BACKGROUND
Our previous studies revealed that the mRNA encoded by BP1, a member of the homeobox gene superfamily of transcription factors, was expressed in leukemia and infiltrating breast ductal carcinoma (IDC). This study investigated the immunohistochemical profile of BP1, to determine whether the expression of BP1 protein correlated with breast tumor progression and invasion and whether BP1 was co-localized with erbB2.


METHODS
Paraffin sections from normal reduction mammoplasties (n = 34) and a variety of in situ and invasive breast cancers (n = 270) were either singly immunostained for BP1, or doubly immunostained for BP1 plus either erbB2 or Ki-67.


RESULTS
The prevalence of BP1 positive cells and the intensity of BP1 immunoreactivity increased with the extent of ductal proliferation and carcinogenesis. BP1 expression was barely detectable in normal reduction mammoplasties compared to distinct staining in 21, 46, and 81% of hyperplastic, in situ, and infiltrating lesions, respectively. In cases with co-existing normal, hyperplastic, in situ, and invasive lesions, the tumor cells of the invasive lesions consistently showed the highest frequency and the highest intensity of BP1 immunostaining, followed by in situ tumor cells. Double immunostaining revealed that BP1 co-localized with a subset of erbB2 positive cells in all 15 in situ and IDC tumors examined, and that BP1 positive cells had a substantially higher proliferation rate than morphologically similar cells without BP1 expression.


CONCLUSIONS
These findings suggest that BP1 is an important upstream factor in an oncogenic pathway, and that expression of BP1 may reliably reflect or directly contribute to tumor progression and/or invasion.
Man
Yan-gao
YG
Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, The George Washington University Medical Center, 2300 Eye Street, Washington, DC 20037, USA.
Fu
Sidney W
SW
Schwartz
Arnold
A
Pinzone
Joseph J
JJ
Simmens
Samuel J
SJ
Berg
Patricia E
PE
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis*
C105304:DLX4 protein, human; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors