Nassar Aziza, Radhakrishnan Anu, Cabrero Isabel A, Cotsonis George, Cohen Cynthia
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Appl Immunohistochem Mol Morphol. 2007 Sep;15(3):255-9. doi: 10.1097/01.pai.0000213130.63417.b3.
Lipoxygenases (LOX) and cyclooxygenases (COX) are key mediators of arachidonic acid metabolism. Recently, studies have reported that human breast carcinomas aberrantly express LOX and cyclooxygenase-2 (COX-2), and that decreased levels of 15-lipoxygenase (15-LOX) and raised levels of COX-2 and 12-LOX have prognostic value in patients with breast cancer. 15-LOX was significantly reduced with increasing stage, and in patients who developed metastatic disease, local recurrence, and/or died. With high COX-2, patients developed local recurrence, died from breast cancer and had reduced disease-free and disease-related overall survival in estrogen receptor (ER)-negative but not ER-positive disease. COX-2 expression is also associated with increased angiogenesis, lymph node metastasis, and Her2-neu overexpression. The purpose of this study is to evaluate COX-2 expression in breast cancer and to determine its correlation with prognostic parameters and outcome. Five tissue microarrays were constructed from 43 breast carcinomas and 5 normal breast tissues, represented by 1 mm cores in triplicate from each of 3 foci. Tissue microarray cores were immunostained with monoclonal COX-2. Expression was assessed as intensity and scored as percentage of cells positive. Prognostic parameters and follow-up information were obtained from the hospital records of Mexican Oncology Hospital, Mexico, where the carcinomas were diagnosed. Ninety-five percent (41/43) of the breast carcinomas showed cytoplasmic COX-2 expression. COX-2 intensity and percentage of cells positive correlated significantly with size of carcinoma (P=0.0271; P=0.0539, respectively). COX-2 intensity correlated significantly with histologic grade (P=0.0182). COX-2 did not correlate with outcome (disease-free and overall survival). There was no significant correlation between COX-2 and ER. In conclusion, COX-2 correlates with poor prognostic markers in breast cancer (large tumor size and high tumor grade), but not with outcome. The therapeutic value of COX-2 inhibitors in COX-2 positive breast cancer patients requires further investigation.
脂氧合酶(LOX)和环氧化酶(COX)是花生四烯酸代谢的关键介质。最近,研究报告称,人类乳腺癌异常表达LOX和环氧化酶-2(COX-2),并且15-脂氧合酶(15-LOX)水平降低以及COX-2和12-LOX水平升高对乳腺癌患者具有预后价值。随着分期增加,以及在发生转移性疾病、局部复发和/或死亡的患者中,15-LOX显著降低。COX-2水平高的患者会出现局部复发,死于乳腺癌,并且在雌激素受体(ER)阴性而非ER阳性疾病中,无病生存期和与疾病相关的总生存期缩短。COX-2表达还与血管生成增加、淋巴结转移和Her2-neu过表达相关。本研究的目的是评估COX-2在乳腺癌中的表达,并确定其与预后参数和结局的相关性。从43例乳腺癌和5例正常乳腺组织构建了5个组织微阵列,每个组织微阵列由来自3个病灶的1毫米芯样重复3次组成。组织微阵列芯样用抗COX-2单克隆抗体进行免疫染色。根据强度评估表达情况,并将阳性细胞百分比作为评分。预后参数和随访信息来自墨西哥肿瘤医院的医院记录,这些癌症在此处被诊断。95%(41/43)的乳腺癌显示出COX-2的细胞质表达。COX-2强度和阳性细胞百分比与癌大小显著相关(分别为P = 0.0271;P = 0.0539)。COX-2强度与组织学分级显著相关(P = 0.0182)。COX-2与结局(无病生存期和总生存期)无关。COX-2与ER之间无显著相关性。总之,COX-2与乳腺癌的不良预后标志物(大肿瘤大小和高肿瘤分级)相关,但与结局无关。COX-2抑制剂在COX-2阳性乳腺癌患者中的治疗价值需要进一步研究。