Richardsen Elin, Uglehus Rebecca Dale, Johnsen Stein Harald, Busund Lill-Tove
Department of Clinical Pathology, University Hospital of Northern Norway, Tromsø, Norway.
BMC Res Notes. 2012 Feb 21;5:110. doi: 10.1186/1756-0500-5-110.
The immune system has paradoxical roles during cancer development and the prognostic significance of immune modulating factors is controversial. The aim of this study was to determine the expression of cyclooxygenase 2 (COX-2), transforming growth factor-beta (TGF- beta), interleukin-10 (IL-10) and their prognostic significance in breast cancers. Ki67 was included as a measure of growth fraction of tumor cells.
On immunohistochemical stained slides from 38 breast cancer patients, we performed digital video analysis of tumor cell areas and adjacent tumor stromal areas from the primary tumors and their corresponding lymph node metastases. COX-2 was recorded as graded staining intensity.
The expression of TGF-beta, IL-10 and Ki67 were recorded in tumor cell areas and adjacent tumor stromal areas. In both primary tumors and metastases, the expression of COX-2 was higher in the tumor stromal areas than in the tumor cell areas (both P < 0.001). High stromal staining intensity in the primary tumors was associated with a 3.9 (95% CI 1.1-14.2) times higher risk of death compared to the low staining group (P = 0.036). The expression of TGF-beta was highest in the tumor cell areas of both primary tumors and metastases (both P < 0.001). High stromal expression of TGF-beta was associated with increased mortality. For IL-10, the stromal expression was highest in the primary tumors (P < 0.001), whereas in the metastases the expression was highest in tumor cell areas (P < 0.001). High IL-10 expression in tumor- and stromal cell areas of primary tumors predicted mortality. Ki67 was higher expressed in tumor stromal areas of the metastases, and in tumor cell areas of the primary tumors (P < 0.001). Ki67 expression in tumor cell areas and stromal areas of the metastases was independently associated with breast cancer mortality.
Stromal expression of COX-2, TGF-beta and Ki67 may facilitate tumor progression in breast cancer.
免疫系统在癌症发展过程中具有矛盾的作用，免疫调节因子的预后意义存在争议。本研究的目的是确定环氧化酶2（COX-2）、转化生长因子-β（TGF-β）、白细胞介素-10（IL-10）在乳腺癌中的表达及其预后意义。纳入Ki67作为肿瘤细胞增殖分数的指标。
在38例乳腺癌患者的免疫组化染色切片上，我们对原发肿瘤及其相应淋巴结转移灶的肿瘤细胞区域和相邻肿瘤间质区域进行了数字视频分析。COX-2记录为分级染色强度。
在肿瘤细胞区域和相邻肿瘤间质区域记录到TGF-β、IL-10和Ki67的表达。在原发肿瘤和转移灶中，COX-2在肿瘤间质区域的表达均高于肿瘤细胞区域（均P<0.001）。与低染色组相比，原发肿瘤中高间质染色强度与死亡风险高3.9倍（95%CI 1.1-14.2）相关（P=0.036）。TGF-β在原发肿瘤和转移灶的肿瘤细胞区域表达最高（均P<0.001）。TGF-β高间质表达与死亡率增加相关。对于IL-10，间质表达在原发肿瘤中最高（P<0.001），而在转移灶中，表达在肿瘤细胞区域最高（P<0.001）。原发肿瘤的肿瘤和间质细胞区域高IL-10表达可预测死亡率。Ki67在转移灶的肿瘤间质区域以及原发肿瘤的肿瘤细胞区域表达较高（P<0.001）。转移灶的肿瘤细胞区域和间质区域的Ki67表达与乳腺癌死亡率独立相关。
COX-2、TGF-β和Ki67的间质表达可能促进乳腺癌的肿瘤进展。
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