B7-h4 is highly expressed in ductal and lobular breast cancer.
OBJECTIVE
This study was designed to investigate the expression of B7-H4 protein, a member of the B7 family that is involved in the regulation of antigen-specific immune responses, in normal breast and in primary and metastatic breast carcinomas.


METHODS
Archival formalin-fixed tissue blocks from breast cancers and normal somatic tissues were evaluated for B7-H4 expression by immunohistochemistry with manual and automated image analysis. The proportion of B7-H4-positive cells and the intensity of B7-H4 staining were compared with histologic type, grade, stage, hormone receptor status, and HER-2/neu status.


RESULTS
B7-H4 was detected in 165 of 173 (95.4%) primary breast cancers and in 240 of 246 (97.6%) metastatic breast cancers. B7-H4 staining intensity was greater in invasive ductal carcinomas [24.61 relative units (RU)] and in invasive lobular carcinomas (15.23 RU) than in normal breast epithelium (4.30 RU, P = 0.0003). Increased staining intensity was associated with negative progesterone receptor status (P = 0.014) and history of neoadjuvant chemotherapy (P = 0.004), and the proportion of B7-H4-positive cells was associated with negative progesterone receptor (P = 0.001) and negative HER-2/neu (P = 0.024) status. However, there was no statistically significant relationship between the proportion of B7-H4-positive cells or staining intensity and grade, stage, or other clinicopathologic variables. Low levels of B7-H4 expression were also detected in epithelial cells of the female genital tract, lung, pancreas, and kidney, but B7-H4 was generally absent in most other normal somatic tissues.


CONCLUSIONS
The nearly ubiquitous expression of B7-H4 in breast cancer, independent of tumor grade or stage, suggests a critical role for this protein in breast cancer biology.
Tringler
Barbara
B
Department of Pathology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
Zhuo
Shaoqiu
S
Pilkington
Glenn
G
Torkko
Kathleen C
KC
Singh
Meenakshi
M
Lucia
M Scott
MS
Heinz
David E
DE
Papkoff
Jackie
J
Shroyer
Kenneth R
KR
D000328:Adult; D000368:Aged; D018122:B7-1 Antigen / Q000096:biosynthesis*; D001940:Breast / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D018122:B7-1 Antigen; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human