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
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DOI：
10.1073/pnas.0709802104
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发表时间：
2007-12-04
影响因子：
11.1
通讯作者：
Allison, James P.
中科院分区：
文献类型：
--
作者：
Zang, Xingxing;Thompson, R. Houston;Allison, James P.
B7-H3和B7x是最近发现的B7-CD28家族成员，被认为通过负共刺激抑制外周免疫反应。我们评估了它们在人类前列腺癌中的潜在表达，使用了一大批患者，并进行了7年的随访。我们确定了1985年至2003年间接受根治性前列腺切除术的823例患者的可用组织。用抗B7-H3和-B7x抗体对组织芯片切片进行免疫组织化学染色。肿瘤细胞免疫反应的百分比和强度由两位泌尿外科病理学家盲法评估，并进行结果分析。B7-H3和B7x均为高表达，93%和99%的肿瘤有异常表达。肿瘤细胞每种分子染色阳性的中位数为80%。B7-H3和B7x分别有212例(26%)和120例(15%)呈强阳性。B7-H3和B7x表达强度高的患者在手术时疾病扩散的可能性显著增加(P<；0.001和P=0.005)。此外，B7-H3和B7x高表达的患者临床肿瘤复发(P<；0.001和P=0.005)和癌症特异性死亡(分别为P=0.004和P=0.04)的风险显著增加。据我们所知，我们提出了在人类恶性肿瘤中对B7家族分子进行的最大规模的研究，并对前列腺癌中的B7x进行了以前未描述的评估。B7-H3和B7x在前列腺癌中大量表达，与疾病扩散和预后不良有关。鉴于B7-H3和B7x提出的免疫抑制机制，这些分子是前列腺癌治疗操作的有吸引力的靶点。
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.