Chai Fan, Liang Yan, Bi Jiong, Chen Li, Zhang Fan, Cui Youhong, Bian Xiuwu, Jiang Jun
Breast Disease Center, Southwest Hospital, Third Military Medical University Chongqing 400038, China.
Laboratory of General Surgery, First Affiliated Hospital, Sun Yet-Sen University Guangzhou 510080, China.
Int J Clin Exp Pathol. 2014 Oct 15;7(11):7834-43. eCollection 2014.
REGgamma (REGγ) has been recently found in several types of human cancer, however, its clinical significance in metastasis and prognosis of breast cancer remains unknown. In this study, immunohistochemical staining and western blot analysis were performed to evaluate REGγ expression in both mouse and human breast cancer specimens. We found that in MMTV-PyMT mice, 14 out of 20 (70%) mouse mammary carcinomas were REGγ positive, which was significantly higher than control (0/20, 0%, P < 0.001) and lower than metastatic lung tumour (20/20, 100%, P = 0.027). Further investigation for REGγ expression in 136 human breast cancer tissues with the paired peritumoural normal breast tissues and 140 breast benign disease tissue samples showed that REGγ was undetectable in normal breast tissues and nonmetastatic axillary lymph nodes (ALNs), whereas 111 out of 136 (81.6%) breast cancer tissue samples were REGγ positive, which was significantly higher than breast benign disease tissues (9/140, 6.4%, P < 0.001) and lower than metastatic ALNs (116/116, 100%, P < 0.001). The 5-year disease-free and overall survivals of patients with negative/low level of REGγ were significantly higher than those of patients with high level of REGγ (P < 0.05). Cox regression analyses further indicated that REGγ could serve as a novel independent prognostic factor for breast cancer (OR = 4.369, P = 0.008). Our results suggest that the high expression of REGγ might predict metastasis and poor prognosis in breast cancer.
最近在几种人类癌症中发现了REGγ（REGγ），然而，其在乳腺癌转移和预后中的临床意义尚不清楚。在本研究中，进行了免疫组织化学染色和蛋白质印迹分析，以评估REGγ在小鼠和人类乳腺癌标本中的表达。我们发现，在MMTV-PyMT小鼠中，20只小鼠乳腺癌中有14只（70%）REGγ呈阳性，这显著高于对照组（0/20，0%，P<0.001），低于转移性肺肿瘤（20/20，100%，P = 0.027）。对136例人类乳腺癌组织及其配对的瘤旁正常乳腺组织和140例乳腺良性疾病组织样本中REGγ表达的进一步研究表明，正常乳腺组织和非转移性腋窝淋巴结（ALN）中未检测到REGγ，而136例乳腺癌组织样本中有111例（81.6%）REGγ呈阳性，这显著高于乳腺良性疾病组织（9/140，6.4%，P<0.001），低于转移性ALN（116/116，100%，P<0.001）。REGγ阴性/低水平患者的5年无病生存率和总生存率显著高于REGγ高水平患者（P<0.05）。Cox回归分析进一步表明，REGγ可作为乳腺癌的一个新的独立预后因素（OR = 4.369，P = 0.008）。我们的结果表明，REGγ的高表达可能预示着乳腺癌的转移和不良预后。
