Paracrine influences from fibroblasts derived from different sources of breast tissue on epithelial breast cancer cell growth in vitro were investigated. Medium conditioned (CM) by fibroblasts derived from tumours, adjacent normal breast tissue, and normal breast tissue obtained from reduction mammoplasty or from skin tissue significantly stimulated the growth of the steroid-receptor positive cell lines MCF-7 and ZR 75.1. The proliferation index (PI) on MCF-7 cells with CM from fibroblasts derived from breast tumour tissue was significantly higher than that obtained with fibroblasts derived from adjacent normal breast tissue (2p less than 0.05, n = 8). The PI obtained with CM from normal fibroblast cultures from reduction mammoplasty tissue, like normal tissue adjacent to the tumour, fell in the lower range of values. Skin fibroblast, like tumour tissue derived fibroblast, CM caused a high range PI. MDA-MB-231 and Evsa-T, two steroid-receptor negative cell lines, showed only a minor growth stimulatory responses with some of the fibroblast CM's. Evsa-T was occasionally inhibited by CM's. In conclusion, stromal factors play a role in the growth regulation of human breast cancer cells. The effects on cancer cell growth are, however, varying depending on the source of the stroma and the characteristics of the epithelial tumour cells.

Insulin-like growth factors are involved in the paracrine growth regulation of human breast tumor cells. IGF2 is imprinted in most tissues, and shows expression of the paternal allele only. To investigate whether disruption of this monoallelic IGF2 expression is involved in breast cancer development, a series of primary tumors and adjacent, histologically normal, breast tissue samples, as well as matched primary in vitro fibroblast cultures were studied. Biallelic expression (partial) of IGF2 was found in the majority of in vivo samples, and corresponding fibroblast cultures, while monoallelic expression was found in a normal breast sample. In contrast, H19, a closely apposed, but reciprocally imprinted gene, assumed to be regulated by a common control element, showed retention of monoallelic H19 expression in all in vivo and in the majority of in vitro samples. These data indicate that IGF2, but not H19, is prone to loss of imprinting in breast cancer.z 1998 Federation of European Biochemical Societies.

The platelet-derived growth factor a-receptor 1.5 kb transcript: Target for molecular detection of testicular germ cell tumours of adolescents and adults. APMIS 106: 207-215, 1998. An accurate and relatively simple method to detect testicular germ cell tumours of adolescents and adults (TGCTs) could be useful for early detection and may help to avoid unnecessary orchidectomies. We report a highly sensitive reverse-transcription polymerase chain reaction assay for the 1.5 kb transcript of the platelet-derived growth factor-a receptor for molecular diagnosis of TGCTs. As a simulation of the clinical application of the assay the approach was applied on through-cut-biopsies from orchidectomy specimens. In a series of 31 specimens, the 1.5 kb transcript was detected in all samples containing either carcinoma in situ, or an invasive TGCT, with mature teratoma as only exception. No expression was detected in normal parenchyma. On the basis of the through-cut-biopsies the assay shows a sensitivity of 0.87 and a specificity of 1 .OO. The positive and negative predictive values of the test are 1 .OO and 1 .OO. For carcinoma in situ alone these values are 0.86, 1 .OO, 1 .OO, and 0.80, respectively. The figures at least equal the results obtained with the most sensitive morphological/ enzyme-histochemical study of duplicate biopsies. We conclude that the 1.5 kb transcript of the platelet-derived growth factor-a receptor is a useful molecular marker for TGCTs, and therefore of interest in a clinical setting.

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