Constitutive nitric oxide synthase is diffusely expressed in endometrial carcinomas

Constitutive nitric oxide synthase (cNOS) plays an important role in numerous physiologic as well as Jathophysiologic processes including mutagenesis. Investigations have recently been directed toward exploring the role of cNOS in the palhogenesis of human malignancies. This study was designed to examine the expression of cNOS in endometrial carcinomas. Formalin fixed-paraffin embedded tissue Sections from 50 endometrial tumors (42 adenocarcinomas, 4 serous papillary carcinomas, 2 clear cell carcinomas, 2 adenosquamous carcinomas) were immunostained using a commercially-available monoclonal antibody against cNOS. Localization of staining to the cytoplasm and nuclei was graded. Overall staining intensity was graded on a 0-3+ scale, while frequency of cNOS expression was recorded as the percentage of immunoreactive cells. Benign endometrial glands within adjacent tissue to the tumor samples demonstrated moderate mean cytoplasmic [intensity 1.4+ (range 0-3+), frequency 42.8% (range 0-100%)( and weak nuclear [intensity 1.0+ (range 0-3+), frequency 9.1% (range 0-35%)] staining. While cNOS expression was most prominent in epithelial cells, weak expression was also noted in endometrial stroma, myometrial smooth muscle, blood vessel walls, and cndothelium. Areas of hyperplastic endometrial glands adjacent to the tumors demonstrated a similiar pattern of diffuse cNOS immunoreactivity. We found a range of cNOS expression in endometrial carcinomas which was diffusely Expressed. No statistically significant difference in either frequency or intensity of cNOS expression and different histologie subtypes was noted. Within the endometrioid histopathology, no apparent correlation was found between cNOS expression and tumor stage, grade, depth of myometrial invasion, extension to the lower uterine segment or cervix, lymph node or distant métastases, recurrence, or final patient status. Thus, cNOS expression, which is limited almost exclusively to glandular elements of normal endometrium, becomes diffusely expressed in hyperplastic endometrium, and endometrial carcinoma.