Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas Journal Article


Authors: Zang, X.; Sullivan, P. S.; Soslow, R. A.; Waitz, R.; Reuter, V. E.; Wilton, A.; Thaler, H. T.; Arul, M.; Slovin, S. F.; Wei, J.; Spriggs, D. R.; Dupont, J.; Allison, J. P.
Article Title: Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas
Abstract: B7-H3 and B7x are members of the B7 family of immune regulatory ligands that are thought to attenuate peripheral immune responses through co-inhibition. Previous studies have correlated their overexpression with poor prognosis and decreased tumor-infiltrating lymphocytes in various carcinomas including uterine endometrioid carcinomas, and mounting evidence supports an immuno-inhibitory role in ovarian cancer prognosis. We sought to examine the expression of B7-H3 and B7x in 103 ovarian borderline tumors and carcinomas and study associations with clinical outcome. Using immunohistochemical tissue microarray analysis on tumor specimens, we found that 93 and 100% of these ovarian tumors express B7-H3 and B7x, respectively, with expression found predominantly on cell membranes and in cytoplasm. In contrast, only scattered B7-H3-and B7x-positive cells were detected in non-neoplastic ovarian tissues. B7-H3 was also expressed in the endothelium of tumor-associated vasculature in 44% of patients, including 78% of patients with high-stage tumors (FIGO stages III and IV), nearly all of which were high-grade serous carcinomas, and 26% of patients with low-stage tumors (FIGO stages I and II; P0.001), including borderline tumors. Analysis of cumulative survival time and recurrence incidence revealed that carcinomas with B7-H3-positive tumor vasculature were associated with a significantly shorter survival time (P0.02) and a higher incidence of recurrence (P0.03). The association between B7-H3-positive tumor vasculature and poor clinical outcome remained significant even when the analysis was limited to the high-stage subgroup. These results show that ovarian borderline tumors and carcinomas aberrantly express B7-H3 and B7x, and that B7-H3-positive tumor vasculature is associated with high-grade serous histological subtype, increased recurrence and reduced survival. B7-H3 expression in tumor vasculature may be a reflection of tumor aggressiveness and has diagnostic and immunotherapeutic implications in ovarian carcinomas. © 2010 USCAP, Inc. All rights reserved.
Keywords: adult; cancer survival; human tissue; aged; middle aged; survival rate; unclassified drug; major clinical study; cancer recurrence; advanced cancer; cancer incidence; neoplasm staging; adenocarcinoma; ovarian cancer; antigen expression; ovarian neoplasms; tumor markers, biological; endothelium cell; ovary; immunoenzyme techniques; survival time; endothelium, vascular; cell membrane; ovary carcinoma; cytoplasm; tissue array analysis; antigens, cd; endothelium; tumor vascularization; serous carcinoma; b7 antigen; fluorescent antibody technique, indirect; co-inhibition; co-stimulation; receptors, immunologic; b7 h3 antigen; t cell; antigens, cd80; b7; tumor vasculature
Journal Title: Modern Pathology
Volume: 23
Issue: 8
ISSN: 0893-3952
Publisher: Nature Publishing Group  
Date Published: 2010-08-01
Start Page: 1104
End Page: 1112
Language: English
DOI: 10.1038/modpathol.2010.95
PUBMED: 20495537
PROVIDER: scopus
PMCID: PMC2976590
DOI/URL:
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: MODPE" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Andrew Wilton
    27 Wilton
  2. Susan Slovin
    184 Slovin
  3. Jakob Dupont
    64 Dupont
  4. Xingxing Zang
    14 Zang
  5. Rebecca Waitz
    13 Waitz
  6. Robert Soslow
    643 Soslow
  7. James P Allison
    129 Allison
  8. Joyce I Wei
    5 Wei
  9. David R Spriggs
    314 Spriggs
  10. Victor Reuter
    913 Reuter
  11. Howard T Thaler
    193 Thaler
  12. Manonmani Arul
    3 Arul