Nucleolar organizer regions as markers of endometrial proliferation: a study of normal, hyperplastic, and neoplastic...

Nucleolar organizer regions (NORs) are loops of DNA that transcribe to ribosomal RNA. They can be visualized as intranuclear black dots by histochemical staining with a colloid silver solution. We applied this method to 78 sections of endometrial tissue obtained either from curettage or from hysterectomy specimens. The histological diagnoses were as follows: normal proliferative (N = 9) or secretory (N = 5) endometrium, simple hyperplasia (N = 10), complex hyperplasia (N = 18), atypical hyperplasia (N = 8), and adenocarcinoma (N = 28). Mean silver-stained NOR (AgNOR) counts per cell were 3.2 (standard error of the mean [SEM], 0.2) in normal proliferative and 2.7 (SEM, 0.2) in normal secretory epithelium, and increased to 4.1 (SEM, 0.3) in simple hyperplasia, to 5.4 (SEM, 0.4) in complex hyperplasia, to 8.1 (SEM, 0.7) in atypical hyperplasia, and finally to 10.0 (SEM, 0.5) in endometrial carcinoma. The differences were significant (one-factor analysis of variance [ANOVA], P < .001). A slight increase but no significant difference was seen between the mean AgNOR counts in endometrial carcinomas of different histological grades. Our study suggests that AgNOR counts are reliable markers of endometrial proliferation and allow a clear distinction between benign, premalignant, and malignant epithelial changes. Our AgNOR findings in endometrial hyperplasia support the concept of various degrees of hyperplasia that can be differentiated on morphological grounds.