Cox-2, EGFR, and ERBB-2 Expression in Cervical Intraepithelial Neoplasia and Cervical Cancer Using an Automated Imaging System

Abstract

We hypothesized that the activation of cyclooxygenase (COX)-2, epidermal growth factor receptor (EGFR), and ErbB-2 signaling is required for cervical intraepithelial neoplasia (CIN) lesions to progress to cervical cancer. A retrospective analysis was performed in 179 patients with Stage I squamous cell carcinoma (SCC) and 233 patients with CIN (112 CIN I, 47 CIN II, and 74 CIN III). COX-2, EGFR, and ErbB-2 expression was analyzed by immunohistochemistry using the ACIS III automated imaging system. The mean expression of COX-2, EGFR, and ErbB-2 was compared between the various stages of CIN and SCC. COX-2 mean expression was predominantly cytoplasmic, increasing significantly from CIN I to CIN II, CIN III, and SCC (P<0.001). EGFR mean expression also rose significantly during tumor progression from CIN I to SCC (P=0.001). CIN I samples were negative for ErbB-2 expression. CIN II, CIN III, and SCC were considered positive for ErbB-2 expression in 2.2%, 14%, and 16.2% of cases, respectively. There was also a statistically significant correlation between increase of ErbB-2 positivity from CIN to SCC. We conclude that COX-2, EGFR, and ErbB-2 expression increase significantly during the progression of CIN to cancer.

Clinicopathology of EpCAM and EGFR in human epithelial ovarian carcinoma

“…In physiological processes, EGFR regulates cell differentiation and the cell cycle, and also promotes repair of wound tissue. In pathological processes, overexpression of EGFR has been observed in a variety of human cancers, such as breast, gastric, and cervical cancers [17-19]. The overexpression of EGFR continuously transmits signals to cells, which interfere with the normal regulation of cell differentiation and cycle, which in turn contribute to cells’ continued proliferation and malignant transformation [20].…”

Taurocholate Induces Cyclooxygenase-2 Expression via the Sphingosine 1-phosphate Receptor 2 in a Human Cholangiocarcinoma Cell Line

“…Activation of S1PR2-COX-2 is a key enzyme involved in production of prostaglandins and has been implicated in various cell transformations including cholangiocytes (21)(22)(23)(24)(25). Previous studies reported that CBAs induced COX-2 expression and promoted growth in human CCA cells in culture (15,16).…”

Cyclooxygenase-2 and β-Catenin as Potential Diagnostic and Prognostic Markers in Endometrial Cancer

“…Cox2, which is involved in inflammatory processes, has been found to play a key role in prostaglandin biosynthesis (8,9). Generally, the cox2 protein is only expressed in a limited number of cell types, whereas overexpressed in a variety of malignant tumors, suggesting its possible role in carcinogenesis (6,(10)(11)(12)(13)(14)(15). Moreover, several mediatory factors, such as tumor promoters, proinflammatory cytokines and growth factors, have been reported to induce the upregulation of cox2 expression (16).…”