Role of Cyclooxygenase 2 (COX-2) in Prognosis of Breast Cancer

Abstract

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 . 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.

Exogenous hydrogen sulfide exerts proliferation/anti-apoptosis/angiogenesis/migration effects via amplifying the activation of NF-κB pathway in PLC/PRF/5 hepatoma cells

“…In our observational study, treatment with 500 µmol/l NaHS for 24 h obviously promoted protein COX-2 secretion in PLC/PRF/5 hepatoma cells. Importantly, accumulating evidence has demonstrated that cyclooxygenase (COx)-2 is overexpressed in several types of cancers cells (73)(74)(75) including hepatocellular carcinoma (HCC) (76). COX-2 expression in cells and animal models is closely associated with tumor cell growth and is a crucial molecule in the development of malignant tumors, including promotion of angiogenesis (77), anti-apoptotic effects (78), invasiveness of tumor cells (74), and tumor cell proliferation (79), demonstrating that COX-2 pathway is implicated in NaHS-induced PLC/PRF/5 hepatoma cell proliferation, anti-apoptosis, angiogenesis and migration.…”

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

“…COX-2 expression was used to predict whether tumors were likely to metastasize or, in the case of ductal carcinoma in situ (DCIS), to recur. In a study of high-grade breast tumors, COX-2 expression was predictive for lymph node metastasis in tumors greater than 20 mm in size [59,60]. In DCIS, COX-2 expression was predictive for recurrence [68].…”

“…In several breast cancer studies examining COX-2 expression (mRNA and/or protein by immunohistochemistry), COX-2 was only expressed in tumor, not normal breast tissue, and overall its expression in tumors predicted a worse prognosis [59][60][61][62][63][64][65][66][67]. COX-2 expression was used to predict whether tumors were likely to metastasize or, in the case of ductal carcinoma in situ (DCIS), to recur.…”

“…In breast cancers of varying stage, COX-2 expression was shown to be inversely correlated with ER expression [59,[70][71][72].…”

Effect of Helicobacter pylori on cyclooxygenase-2 and inducible nitric oxide synthase in patients with gastric precancerous lesions and its clinical significance

“…COX-2 is generally produced when the body suffers stimulation, and is involved in the inflammatory response (16). Studies have found an abnormal expression of COX-2 protein in several types of tumor tissues, which suggests that it may be involved in the tumorigenesis and the development and metastasis of cancer (17,18). iNOS is generally produced by macrophages or monocytes and is the main sign of an inflammatory reaction.…”