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Objectives: This study compared p53 expression with B7-H4, a novel cancer biomarker, in pancreatic ductal adenocarcinoma (PDA) resection specimens and in a pilot series of endoscopic ultrasound-guided fine-needle aspirations (EUS-FNAs)., Methods: B7-H4 and p53 expression were evaluated by immunoperoxidase methods in 36 PDA and 15 EUS-FNA specimens and were scored for intensity and proportion of positive cells; cases were then assigned a final sum score., Results: B7-H4 was detected in 33 (92%) of 36 PDA sections, 8 (89%) of 9 cytologically positive EUS-FNAs, and 1 (20%) of 5 cytologically negative EUS-FNAs. p53 was detected in 30 (83%) of 36 PDA sections, 4 (44%) of 9 cytologically positive EUS-FNAs, and 1 (20%) of 5 cytologically negative cases. One EUS-FNA case that was cytologically atypical but not diagnostic of malignancy expressed B7-H4 and p53. Some benign tissue components (intercalated cells/ducts, main pancreatic ducts, and acinar cells) were also positive for B7-H4 and/or p53. Overall expression of B7-H4 in benign tissues, however, was relatively low compared with that seen in most carcinoma cases., Conclusions: B7-H4 was expressed more often in PDA than was p53. Despite potentially problematic expression in benign/normal cells, the 2 markers target different cellular components and demonstrate potential diagnostic use for detection of PDA in resected and EUS-FNA specimens.

B7-H4, a member of the B7 family, is involved in the regulation of antigen-specific immune responses. Its expression in a range of breast pathology and correlation to the number of CD3 and CD8 tumor infiltrating T-lymphocytes in invasive carcinomas were explored. The proportion of B7-H4 positive cells, staining pattern, and intensity were evaluated within diagnostic groups (normal and benign lesional, potentially premalignant and in situ carcinoma, and invasive carcinoma) on archival tissue blocks by immunohistochemistry. The proportion and intensity of B7-H4 expression was progressively increased across the major diagnostic groups. There was a significant association between a high proportion of B7-H4 positive cells in invasive ductal carcinomas and decreased number of tumor infiltrating lymphocytes (P=0.002). The cellular distribution of B7-H4 appears altered in the spectrum of normal to malignant breast. Its overexpression may help cancers avoid immune detection.

Objectives and Methods: B7-H4 (DD-O110), a member of the B7 family, negatively regulates T cell-mediated immune response. Previous studies have shown that B7-H4 is highly expressed in endometrioid ovarian cancers with relatively low levels of expression in normal ovary which was confirmed by Western blot. The present study was designed to localize B7-H4 expression by immunohistochemistry (IHC) in normal endometrium, endometrial hyperplasia and uterine endometrioid adenocarcinoma. The pattern of B7-H4 localization was compared with the IHC detection of CD3 and CD8-positive T lymphocytes and CD14 positive macrophages to investigate the role of B7-H4 in the regulation of tumor immune surveillance. B7-H4 expression was evaluated in apoptotic tumor cells., Results: The proportion and intensity of B7-H4 staining were increased in the progression from normal, hyperplastic and malignant endometrial glandular mucosa. B7-H4 showed a predominantly apical membranous staining (pattern 1) in normal and hyperplastic endometrial epithelium but showed intense circumferential membranous and cytoplasmic staining (pattern 2) in a majority of endometrioid carcinoma cases (p=0.018). The proportion of B7-H4 positive tumor cells and staining intensity was also higher in high risk tumors than in low risk tumors (p=0.001 and p=0.032, respectively). The proportion of B7-H4 positive tumor cells was inversely related to the number of CD3-positive and CD8-positive tumor-associated lymphocytes (TALs). There was a positive correlation between B7-H4 pattern 2 staining and both CD3-positive and CD8-positive tumor-infiltrating lymphocytes (TILs) (p=0.039 and p=0.031, respectively)., Conclusions: B7-H4 is overexpressed in hyperplastic and malignant endometrial epithelium and is correlated with the number T cells associated with the tumor. These results suggest that B7-H4 overexpression may reflect a more aggressive biologic potential and may play a role in tumor immune surveillance mechanisms.

Objectives: Despite great advances in therapeutic management, the mortality rate for ovarian cancer has remained relatively stable over the past 50 years. This study was designed to evaluate the expression of B7-H4 protein, recently identified as a potential molecular marker of breast and ovarian cancer by quantitative PCR analysis, in benign tumors, tumors of low malignant potential and malignant tumors of the ovary., Methods: Archival formalin-fixed tissue blocks from serous, mucinous, endometrioid and clear cell ovarian tumors were evaluated by immunohistochemistry for the distribution of B7-H4 expression, and staining intensity was measured by automated image analysis. Univariate analyses were used to test for statistically significant relationships., Results: B7-H4 cytoplasmic and membranous expression was detected in all primary serous (n = 32), endometrioid (n = 12), and clear cell carcinomas (n = 15), and in all metastatic serous (n = 23) and endometrioid (n = 7) ovarian carcinomas. By contrast, focal B7-H4 expression was detected in only 1/11 mucinous carcinomas. The proportion of positive cells and median staining intensity was greater in serous carcinomas than in serous cystadenomas or serous tumors of low malignant potential, and the differences were statistically significant (P < 0.0001 and P = 0.034, respectively). The median staining intensity was also significantly greater in endometrioid carcinomas than in endometriosis (P = 0.005)., Conclusions: The consistent overexpression of B7-H4 in serous, endometrioid and clear cell ovarian carcinomas and the relative absence of expression in most normal somatic tissues indicates that B7-H4 should be further investigated as a potential diagnostic marker or therapeutic target for ovarian cancer.

Purpose: 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., Experimental Design: 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.