BP1 Expression May Be Indicator of Early Breast Cancer

SAN ANTONIO—Intensity of immunostaining for the gene BP1 (beta protein 1) correlates with breast cancer aggressiveness, and detection of BP1 in otherwise apparently normal tissue specimens may be a marker for early detection of breast cancer, Patricia E. Berg, PhD, said at the 26th San Antonio Breast Cancer Symposium (abstract 41).

Dr. Berg, associate professor of biochemistry and molecular biology, George Washington University Medical Center, reported data comparing BP1 expression in various types of breast cancer with samples from normal breast reduction and with apparently normal breast cells from breast cancer patients.

Dr. Berg said that BP1 is a master regulator gene and part of the homeobox gene superfamily of transcription factors important in early development. The gene maps to chromosome 17q21-22.

Dr. Berg’s group previously reported that the BP1 gene is expressed in the bone marrow of 63% of acute myeloid leukemia (AML) patients. Further research showed that BP1 was activated in 80% of invasive ductal carcinoma patients, whereas adjacent normal cells and most normal control subjects were negative for BP1 expression (Fu et al: Breast Cancer Res 5:82-87, 2003).

The study also showed that BP1 is highly correlated with estrogen-receptor (ER) status. Dr. Berg said that 100% of ER-negative breast tumors were BP1 positive vs 73% of ER-positive tumors (P = .03). Further, among African-American breast cancer patients, who have a higher breast cancer mortality than whites, 89% were BP1 positive, compared with 57% of white patients. "These findings suggest that the expression of BP1 may be associated with breast cancer aggressiveness," she said.

Study Objectives

The objectives of this study were to determine whether protein and mRNA expression of BP1 correlate, and whether BP1 protein is expressed in both invasive ductal carcinomas and in situ lesions. The researchers used a polyclonal antibody to BP1 to immunostain paraffin sections from patients with a variety of in situ and invasive breast lesions (n = 100), and from normal controls who had reduction mammoplasties (n = 34).

Among the normal controls, 12% of samples stained positive for BP1, although less than 5% of the cells in those positive samples were BP1 positive. The number of BP1-positive tumors was 35% in intraductal hyperplasia, 50% in sections from in situ tumors, and 80% in invasive ductal tumors. Interestingly, a subset of cells in invasive and in situ cancers that appeared normal in fact stained positive for BP1.

Stain Intensity

Staining for BP1 was relatively homogenous in invasive ductal carcinoma and heterogenous in ductal carcinoma in situ. "The frequency and intensity of BP1 staining increase with tumor aggressiveness," Dr. Berg said.

In tissues that contain normal, in situ, and invasive tumor cells, she said, the invasive cells stained most intensely for BP1, followed by in situ tumor cells. "Intensity is an indicator of BP1 expression, so the most intensely staining cells, which are also the most aggressive tumors, produce the most BP1 protein."

Further, she stated that activation of BPI in the earliest breast tumors indicates that BP1 may be a useful detector of early breast cancer.