The human H19 gene is frequently overexpressed in myometrium and stroma during pathological endometrial proliferative events

Abstract

We studied the patterns of H19 expression in normal, hyperplastic and neoplastic human uterine tissues. H19 RNAs were detected by an in situ hybridisation technique (ISH). In both normal and pathological conditions, H19 was expressed in stromal and myometrial cells, but never in epithelial cells. 34/48 carcinomas overexpressed H19 compared with the expression in normal tissues. This high expression was frequently observed in the vicinity of malignant epithelial cells. This suggests that the level of H19 RNA synthesis could be the result of epithelium/stroma interactions. We also demonstrated that several cancerous or immortalised breast epithelial cells release factors into the culture medium, which in turn stimulate H19 expression in stromal cells. The level of H19 expression, estimated by ISH, was not significantly correlated with histological type when all types were considered together ( P = 0.108), but was highly correlated to one type of cancer, i.e. carcinomas with an epidermoid component ( P = 0.0015). The level of H19 expression was also strongly correlated with tumour invasion of the reproductive organs ( P = 0.006) and significantly correlated with neoplastic cell invasion of the myometrium ( P = 0.048). In conclusion, our results indicate that H19 overexpression is correlated with the progression of the disease and we propose that this frequent overexpression of the gene in the myometrium and in stroma is a reaction to pathological cell proliferation.