Department of Pathology, University Hospital of Northern Norway, Tromsø, Norway.
Cancer Epidemiol. 2010 Jun;34(3):316-22. doi: 10.1016/j.canep.2010.03.019. Epub 2010 Apr 22.
The immune modulating molecules cyclooxygenase-2 (COX-2), transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10) have regulatory roles in cancer progression. There are conflicting data regarding the roles of these molecules in prostate cancer. To elucidate the prognostic impact of these proteins and provide information on prognosis and treatment, we compared the expression of COX-2, TGF-beta, and IL-10 in prostate cancer specimens with or without metastases. Ki67 was included as a measure of growth fraction of tumor cells.
Digital video analysis images from tumor cell areas and tumor stromal areas were analyzed on formalin fixed, paraffin-embedded and immunohistochemical stained cancer specimens from 59 patients: 32 patients with metastases and 27 patients without clinical, biochemical, or radiological evidence of metastases within 10 years after diagnosis. The expression of COX-2 was scored as negative, weak, moderate, or strong. The expressions of TGF-beta and IL-10 were assessed as proportions of moderately or strongly stained cells. Ki67 was detected as strong nuclear staining in proliferating cells.
In primary cancers in the metastatic group, COX-2, TGF-beta and Ki67 were stronger expressed in epithelial tumor cell and tumor stromal areas compared with non-metastatic cancers (for all markers, p<0.0001). High intensity of COX-2 staining in tumor areas was strongly associated with death from prostate cancer in univariate analyses (hazard ratio [HR] 95% CI, 4.0 (1.1-14.5)). In multivariate analyses, the risk estimate was strengthened but did not reach significance. No associations to death were found for the other markers.
High expression of COX-2, TGF-beta and Ki67 were in metastatic primary prostate carcinoma compared to non-metastatic cancers. High expression of COX-2 was associated to death from prostate carcinoma.
免疫调节分子环氧化酶-2(COX-2)、转化生长因子-β(TGF-β)和白细胞介素-10(IL-10)在癌症进展中具有调节作用。这些分子在前列腺癌中的作用存在相互矛盾的数据。为了阐明这些蛋白的预后影响,并提供预后和治疗信息,我们比较了有或无转移的前列腺癌标本中 COX-2、TGF-β 和 IL-10 的表达。Ki67 被用作肿瘤细胞生长分数的衡量标准。
对 59 例患者的福尔马林固定、石蜡包埋和免疫组织化学染色的癌症标本的肿瘤细胞区和肿瘤间质区的数字视频分析图像进行分析:32 例有转移,27 例无转移,诊断后 10 年内无临床、生化或影像学转移证据。COX-2 的表达评分分为阴性、弱阳性、中度阳性或强阳性。TGF-β 和 IL-10 的表达评估为中度或强染色细胞的比例。Ki67 在增殖细胞中检测到强核染色。
在转移性组的原发性癌症中,与非转移性癌症相比,上皮肿瘤细胞和肿瘤间质区的 COX-2、TGF-β 和 Ki67 表达更强(所有标志物,p<0.0001)。肿瘤区 COX-2 染色强度高与前列腺癌死亡的单因素分析密切相关(风险比[HR]95%可信区间,4.0[1.1-14.5])。多因素分析中,风险估计值增强但未达到显著性。其他标志物与死亡无关。
与非转移性癌症相比,转移性原发性前列腺癌中 COX-2、TGF-β 和 Ki67 的表达较高。COX-2 表达较高与前列腺癌死亡相关。