Immunohistochemical Evaluation of Notch1 in Ovarian Tumours and Its Prognostic Implications

Abstract

BACKGROUND Ovarian cancer is the fifth most common malignancy among women and the second most common gynaecological malignancy. Surface epithelial ovarian tumours constitute two-thirds of all ovarian tumours. Most high-grade serous carcinoma patients gain an initial complete response but eventually succumb to relapse and death leaving the overall survival grim. Therefore, new regimens targeting the pathways involved in metastasis and chemoresistance are essential for the development of more effective therapies. Notch signalling is one of the pleiotropic signalling pathways that plays a key role in differentiation and tissue morphogenesis. It has been observed that this Notch signalling pathway is seen to be deregulated in various cancers. It is thought to have an oncogenic role in ovarian cancer. Our objective in this study is to evaluate the immunohistochemical expression pattern of Notch1 in surface epithelial ovarian tumours and its correlation with the clinicopathological profile. METHODS This study includes a total of 100 cases of borderline and malignant surface epithelial ovarian tumours. Clinical data of the patients were obtained from the medical records section. HPE slides were examined and one representative paraffin block was selected for each patient. IHC of Notch1 was performed and analyzed. The staining pattern for Notch1 was calculated using the Q score. RESULTS Immunohistochemistry (IHC) evaluation of Notch1 in surface epithelial ovarian tumours in this study showed an increased intensity of Notch1 staining in high-grade serous malignant tumours. The grading and staging of tumours were compared with Notch1 expression. Statistical analysis was performed using Spearman Rank order correlation analysis. There was a significant correlation (0.01 level, two-tailed) between the grading and staging of ovarian tumours and Notch1 expression. CONCLUSION Assessing Notch1 expression in ovarian cancer by IHC is a useful tool in view of its clinical applications, development of targeted therapies and as a marker of prognosis. The intensity of the Notch1 stain appears to be directly proportional to the grade of tumour. This may offer a potential targeted therapy against the Notch signalling pathway in tumours that strongly express Notch1.