B7-H4 overexpression in ovarian tumors

Tringler, Barbara; Liu, Wenhui; Corral, Laura G.; Torkko, Kathleen C.; Enomoto, Takayuki; Davidson, Susan A.; Lucia, M. Scott; Heinz, David; Papkoff, Jackie; Shroyer, Kenneth R.

doi:10.1016/j.ygyno.2005.08.060

Cited by 134 publications

(105 citation statements)

References 20 publications

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“…In the context of malignancy, the precise physiologic and pathologic role of B7-H3 expression has yet to be fully elucidated. Transfection of B7-H3 into experimental tumor lines (P815 mastocytoma, Colon-26, and EL-4 lymphoma) has been reported to accelerate in vivo tumor rejection, supporting a net (22,25), uterus (26), and kidney (27). Krambeck et al (27) recently evaluated B7x in 259 patients with renal cell carcinoma, demonstrating that tumor expression of B7x was associated with adverse pathologic features (including advanced tumor size, grade, and stage) and an increased risk of death from disease (27).…”

Section: Discussionmentioning

confidence: 92%

“…Despite mRNA expression in various human tissues, immunohistochemistry (IHC) for B7x fails to reveal detectable protein expression in any healthy human organs (23). In stark contrast, aberrant expression of B7x has been observed in cancers of the breast (22,24), lung (16), ovary (22,25), uterus (26), and kidney (27). Thus, B7x, and perhaps B7-H3, have been proposed as potential therapeutic targets in human malignancy.…”

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confidence: 99%

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B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

Zang

Thompson²,

Al‐Ahmadie³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

345

327

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B7-H3 and B7x are recently discovered members of the B7-CD28 family thought to dampen peripheral immune responses via negative costimulation. We evaluated their potential expression in human prostate cancer using a large cohort of patients with 7 years of follow-up. We identified 823 patients with tissue available treated with radical prostatectomy between 1985 and 2003. Immunohistochemistry was performed on tissue microarray sections using anti-B7-H3 and -B7x. The percentage and intensity of immunoreactivity by tumor cells were blindly evaluated by two urological pathologists, and outcome analyses were conducted. Both B7-H3 and B7x were highly expressed; 93% and 99% of tumors had aberrant expression, respectively. The median percentage of tumor cells staining positive was 80% for each molecule. Strong intensity for B7-H3 and B7x was noted in 212 (26%) and 120 (15%) patients, respectively. Patients with strong intensity for B7-H3 and B7x were significantly more likely to have disease spread at time of surgery (P < 0.001 and P ‫؍‬ 0.005, respectively). Additionally, patients with strong intensity for B7-H3 and B7x were at significantly increased risk of clinical cancer recurrence (P < 0.001 and P ‫؍‬ 0.005) and cancer-specific death (P ‫؍‬ 0.004 and P ‫؍‬ 0.04, respectively). To our knowledge, we present the largest investigation of B7 family molecules in a human malignancy and a previously undescribed evaluation of B7x in prostate cancer. B7-H3 and B7x are abundantly expressed in prostate cancer and associated with disease spread and poor outcome. Given the proposed immune-inhibitory mechanisms of B7-H3 and B7x, these molecules represent attractive targets for therapeutic manipulation in prostate cancer.immune tolerance ͉ prostatic neoplasms ͉ treatment outcome ͉ biological tumor markers

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Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 99%

B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

Zang

Thompson²,

Al‐Ahmadie³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

345

327

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“…To date, only one study has attempted to correlate aberrant tumor expression of B7-H4 with clinical outcome. Tringler et al (8) recently evaluated expression of B7-H4 in various forms of ovarian tumors (i.e., serous, endometrioid, clear cell, and mucinous carcinomas) and found that cytoplasmic and membranous patterns of B7-H4 staining were observed only in invasive carcinomas, not in benign lesions or tumors of low malignant potential. However, owing to the relatively limited number of patient samples investigated for each tumor subtype, tumor B7-H4 expression could not be correlated with ovarian tumor grade, stage, cancer recurrence, or survival (8).…”

mentioning

confidence: 99%

B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival

Krambeck¹,

Thompson²,

Dong³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

279

251

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B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, associations of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio ‫؍‬ 3.05; 95% confidence interval ‫؍‬ 1.51-6.14; P ‫؍‬ 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC.B7-H1 ͉ costimulation ͉ tumor biomarker ͉ immunotherapy ͉ kidney neoplasms

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“…Importantly, 60% of Stage I ovarian tissues and 90% of Stage II tissues stained positive for B7-H4 [96]. Elevated levels of B7-H4 were detected in 45% of early stage cancers at a specificity of 97% using an ELISA assay [85].…”

Section: B7-h4mentioning

confidence: 99%

Early Detection of Ovarian Cancer

Das

Bast

2008

Biomarkers Med.

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Abstract. Despite advances in therapy, ovarian cancer remains the most deadly of the gynecological cancers. Less than 30% of women with advanced stage disease survive long-term. When diagnosed in stage I, up to 90% of patients can be cured with conventional surgery and chemotherapy. At present, only 25% of ovarian cancers are detected in stage I due, in part, to the absence of specific symptoms and to lack of an effective screening strategy. Early detection of ovarian cancer might significantly improve the overall survival rate of women with ovarian cancer if 1) most cancers are clonal and unifocal, arising in the ovary rather than in the peritoneum, 2) metastatic disease results from progression of clinically detectable stage I lesions, and 3) cancers remain localized for a sufficient interval to permit cost-effective screening. Given the prevalence of ovarian cancer, strategies for early detection must have high sensitivity for early stage disease (>75%), but must have extremely high specificity (99.6%) to attain a positive predictive value of at least 10%. Transvaginal sonography (TVS), serum markers and a combination of the two modalities have been evaluated for early detection of ovarian cancer. Among the serum markers, CA125 has received the most attention, but lacks the sensitivity or specificity to function alone as a screening test. Greater specificity can be achieved by combining CA125 and TVS and/or by monitoring CA125 over time. Two stage screening strategies promise to be cost effective, where abnormal serum assays prompt TVS to detect lesions that require laparotomy. Accrual has been completed for a 200,000 woman trial in the United Kingdom that will test the ability of a rising CA125 to trigger TVS and subsequent exploratory surgery. Given the heterogeneity of ovarian cancer, it is unlikely that any single marker will be sufficiently sensitive to provide an effective initial screen. Sensitivity of serum assays might be enhanced by utilizing a panel of biomarkers. Candidate biomarkers have been discovered through empirical development of monoclonal antibodies, studies of gene expression, cloning of gene families and proteomic techniques. The development of technologies that measure multiple serum markers simultaneously, linked to the creation of statistical methods that enhance sensitivity without sacrificing specificity hold great promise.

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B7-H4 overexpression in ovarian tumors

Cited by 134 publications

References 20 publications

B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome

B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival

Early Detection of Ovarian Cancer

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