Jana Debarshi, Sarkar Diptendra Kumar, Ganguly Suvro, Saha Shilpi, Sa Gaurisankar, Manna Asim Kumar, Banerjee Abhirup, Mandal Syamsundar
Comprehensive Breast Service and Breast Cancer Research Unit, Department of Surgery, Institute of Post Graduate Medical Education & Research (IPGME&R) and Seth Sukhlal Karnani Memorial Hospital (SSKM), Kolkata, 700020 India.
Division of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme VII M, Kolkata, 700 054 India.
Indian J Surg Oncol. 2014 Mar;5(1):59-65. doi: 10.1007/s13193-014-0290-y. Epub 2014 Feb 12.
COX-2 regulates tumour growth, invasion and metastasis in breast cancer. This study investigated the association between COX-2 expression in human breast cancer versus the expression of ER, PR, HER-2/neu, as well as its association with other established prognostic indicators like age, menopausal status, tumour size, lymph nodal status, stage, grade, NPI and histological subtype, and aims to validate the role of overexpression of COX-2 as a prognostic marker in patients with breast cancer in Indian subcontinent. In this hospital based study of 123 breast cancer patients (Group-A) and 76 female patients with benign breast disease (Group-B) attending a Comprehensive Breast Clinic at a reputed institute in Eastern India, COX-2 protein expression was measured from breast tissue using the Western Blot Technique. COX-2 mRNA expression was measured by RT-PCR Technique. ER, PR and HER-2/neu status was measured by immunohistochemistry methods. COX-2 was not expressed in the control group. The proportion of COX-2 positive tumours was significantly higher in patients of age >50 years [52(91.2 %), p < 0.01], postmenopausal status [64(90.1 %), p < 0.01], advanced stage of disease (p < 0.01), higher grade (p < 0.01), larger tumors (p < 0.01), metastatic lymph nodes (p < 0.01) and NPI ≥ 5.4 (p < 0.01). COX-2 expression was seen in ER-negative [66(95.7 %), p < 0.01], PR-negative [76(92.7 %), p < 0.01], and HER-2/neu positive tumours [29(100.0 %), p < 0.01]. Risk of COX-2 positivity was found to be 2.74 times more for postmenopausal status, 6.90 times more for large size tumours (≥ 2.5), 34.37 times more for node positive tumours, 9.26 times more with ER negative patients and 5.88 times more for PR negative patients. COX-2 expression is associated with established indicators of poor prognosis such as postmenopausal status, age >50 year, advanced stage of disease, large tumour size, higher grade, lymph node metastasis, NPI ≥ 5.4, ER negativity, PR negativity and HER-2/neu positivity. Thus, COX-2 expression implies aggressive tumour biology, and may play an important role as a prognostic marker.
环氧化酶-2（COX-2）调节乳腺癌的肿瘤生长、侵袭和转移。本研究调查了人类乳腺癌中COX-2表达与雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体2/神经生长因子受体（HER-2/neu）表达之间的关联，以及其与其他已确立的预后指标如年龄、绝经状态、肿瘤大小、淋巴结状态、分期、分级、诺丁汉预后指数（NPI）和组织学亚型之间的关联，旨在验证COX-2过表达作为印度次大陆乳腺癌患者预后标志物的作用。在这项基于医院的研究中，对印度东部一家著名机构综合乳腺诊所的123例乳腺癌患者（A组）和76例乳腺良性疾病女性患者（B组），采用蛋白质免疫印迹技术检测乳腺组织中的COX-2蛋白表达。采用逆转录聚合酶链反应（RT-PCR）技术检测COX-2信使核糖核酸（mRNA）表达。通过免疫组织化学方法检测ER、PR和HER-2/neu状态。对照组未检测到COX-2表达。年龄>50岁的患者中COX-2阳性肿瘤比例显著更高[52例（91.2%），p<0.01]，绝经后状态患者[64例（90.1%），p<0.01]，疾病晚期（p<0.01），高分级（p<0.01），肿瘤较大（p<0.01），有转移淋巴结（p<0.01）以及NPI≥5.4（p<0.01）。在ER阴性[66例（95.7%），p<0.01]、PR阴性[76例（92.7%），p<0.01]和HER-2/neu阳性肿瘤[29例（100.0%），p<0.01]中可见COX-2表达。发现绝经后状态COX-2阳性风险高2.74倍，肿瘤较大（≥2.5）者高6.90倍，淋巴结阳性肿瘤高34.37倍，ER阴性患者高9.26倍，PR阴性患者高5.88倍。COX-2表达与绝经后状态、年龄>50岁、疾病晚期、肿瘤较大、高分级、淋巴结转移、NPI≥5.4、ER阴性、PR阴性和HER-2/neu阳性等已确立的预后不良指标相关。因此，COX-2表达意味着侵袭性肿瘤生物学行为，可能作为一种预后标志物发挥重要作用。
