Increased Notch1 Expression Is Associated With Poor Overall Survival in Patients With Ovarian Cancer

Objective: Despite improvements in surgery and chemotherapy, ovarian cancer remains a deadly disease in need of improved therapies. We have previously shown that Notch1 intracellular domain (NICD) is highly expressed in ovarian cancer. We have also shown that NICD inhibition can lead to growth arrest in ovarian cancer cells. The objective of the current study was to delineate whether NICD expression correlates with prognosis of women with ovarian cancer. Methods: After the institutional review board approval, patients with a diagnosis of primary ovarian cancer between the years 2001 and 2007 who underwent surgery at our institution were identified. Paraffin blocks from the primary ovarian tumor were analyzed, and core samples were obtained to build a tissue microarray. Cytoplasmic NICD expression was assessed by quantitative immunofluorescent morphometry using the automated quantitative analysis system. These results were correlated with clinical and pathology data retrieved from the patient records. Results: We identified 328 patients with primary ovarian cancer during this period. Seventeen percent of patients had stage I, 11% had stage II, 59% had stage III, and 13% had stage IV disease. Most patients (70%) had papillary serous histology, and most (86%) underwent optimal debulking to less than 1 cm of residual disease. High NICD expression was found to correlate strongly with low overall survival (P = 0.001). This effect remained in multivariate analysis (P = 0.023). Conclusions: High expression of NICD in the primary tumor of women with ovarian cancer is an independently poor prognostic factor for overall survival. Further research into the therapeutic inhibition of the Notch1 pathway is warranted.