The H19 gene is expressed within both epithelial and stromal components of human invasive adenocarcinomas

In a previous work, we have isolated the human H19 gene and shown accumulation of transcripts in various human tumors including breast carcinomas (Douc-Rasy et al (1993) Int J Oncol 2, 753-758). Questions arose, after Northern blot results, about the precise H19 mRNA location, specially in normal breast tissues and benign or malign primary breast tumors. Then we performed molecular in situ hybridization to get insight into tissue expression of the H19 gene. Examined resections included one normal tissue, one fibroadenoma and 13 cancers. Results obtained with the H19 probe can be summarized as follows: 1) in normal breast tissues signals were focally observed in epithelial cells, but more predominantly in the palleal tissue which is sensitive to hormones; 2) in the fibroadenoma, fibroblastic cells were extensively labeled at the stroma-epithelium boundary, but epithelial cells were negative; and 3) in primary cancers, eight specimens exhibited signals on stromal cells, one specimen on epithelial cells and four on both epithelial and stromal cells. Data provide the following evidence: 1) usually labeled cells are clustered, either within normal or pathological tissues; 2) the labeling pattern highly differs from one tumor to another; and 3) H19 probe displays very different signals from one cell to another in given compartment of a given tissue section. In conclusion, it seems that a high H19 expression matches the tumor invasion. Our results suggest that the expression of this gene is concerned by the relationships between epithelial and stromal cells, and can reflect peculiar physiological states of the cells. Furthermore, we discuss results showing an abundant expression of H19 gene in some adenocarcinomas of bad prognosis, in the context of the otherwise established tumor-suppressor role of this gene, or the strictly controlled gene dosage, which could be overridden in these particular cases.