National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Am J Clin Pathol. 2010 Jul;134(1):71-9. doi: 10.1309/AJCPRJP39MIDSGBH.
To assess the expression of a cancer-associated fibroblasts (CAFs) marker as an indicator of prognosis, we raised anti-protein gene product 9.5 (PGP9.5) monoclonal antibody against cultured fibroblasts. PGP9.5 expression in cultured normal fibroblasts was increased by transforming growth factor beta stimulation, indicating the phenotypic alteration to activated fibroblast. We immunohistochemically evaluated PGP9.5 expression with the CAFs of 110 colorectal cancer cases under T3 stage. PGP9.5 immunoreactivity in 30% or more of CAFs was defined as high PGP9.5 expression, and the other cases were considered as having low PGP9.5 expression. Patients with high PGP9.5 expression (42.7%) had significantly shorter survival and a higher incidence of recurrence than the low PGP9.5 expression group (P = .002 and P < .001, respectively). Multivariate analysis indicated PGP9.5 expression as an independent prognostic factor for overall and recurrence-free survival partly as well as lymph node metastasis. These results indicate that PGP9.5 expression in CAFs is a helpful finding to represent the overall biologic behavior of advanced colorectal cancer.
为了评估癌症相关成纤维细胞(CAFs)标志物的表达作为预后指标的价值,我们制备了针对培养的成纤维细胞的蛋白基因产物 9.5(PGP9.5)单克隆抗体。转化生长因子β刺激培养的正常成纤维细胞中 PGP9.5 的表达增加,表明其向激活的成纤维细胞表型改变。我们用 T3 期的 110 例结直肠癌病例的 CAFs 进行了 PGP9.5 免疫组织化学评估。将 CAFs 中 30%或更多的 PGP9.5 免疫反应性定义为高 PGP9.5 表达,其他病例则被认为是低 PGP9.5 表达。高 PGP9.5 表达(42.7%)的患者的总生存率和复发率显著低于低 PGP9.5 表达组(P=.002 和 P<.001)。多变量分析表明 PGP9.5 表达是总生存率和无复发生存率的独立预后因素,也是淋巴结转移的独立预后因素。这些结果表明,CAFs 中的 PGP9.5 表达有助于代表晚期结直肠癌的整体生物学行为。