The role and prognostic value of inducible nitric oxide synthase (iNOS) and interleukin-33 (IL-33) in serous and mucinous epithelial ovarian tumours.

Understanding different mechanisms contributing to the aggressive behaviour of epithelial ovarian cancer (EOC) is a large challenge. Interaction between inflammation, immunity and carcinogenesis occurs in different cancers; however, the potential roles of different molecules involved in these processes in relation to ovarian carcinogenesis were not fully investigated. Inducible nitric oxide synthase (iNOS) and interleukin-33 (IL-33) are implicated in carcinogenesis. iNOS is an NOS isoform that generates nitric oxide, which plays important roles in various stages of carcinogenesis. IL-33 is a cytokine implicated in modulation of anti-tumour immunity and tumour growth. This work aimed at studying the immunohistochemical expression of iNOS and IL-33 in serous and mucinous epithelial ovarian tumours to investigate their role and prognostic significance. Immunohistochemical expressions of iNOS and IL-33 were assessed in 90 patients with epithelial ovarian tumours (45 serous and 45 mucinous tumours, categorized as benign, borderline, and malignant tumours). iNOS and IL-33 showed significantly higher expressions in borderline and malignant serous and mucinous tumours compared to benign ones (p=0.0001). The differences between borderline and malignant tumours were statistically insignificant (p=0.2351&0.6321). iNOS showed significantly higher expression with increasing tumour grade in malignant mucinous tumours (p=0.0011). IL-33 showed significantly higher expression with increasing tumour grade in both malignant serous and mucinous tumours (p=0.0074 and 0.0007). Upregulation of iNOS and IL-33 expression in borderline and malignant epithelial ovarian tumours indicates their involvement in the development and progression of EOC, and their increased expression in less differentiated cancers suggests their association with poor prognosis in this category of tumours.