STROMAL IGF-II MESSENGER-RNA IN BREAST-CANCER - RELATIONSHIP WITH PROGESTERONE-RECEPTOR EXPRESSED BY MALIGNANT EPITHELIAL-CELLS

In breast cancer, insulin-like growth factor II (IGF-II) is stromal in origin and is considered an important regulator of tumour epithelium growth. The presence of progesterone receptor (PR) is expression of an intact oestrogen regulatory pathway of breast malignant epithelial ce lls and represents a parameter of cell differentiation in breast cance r. In this study we have examined the relationship between IGF-II mRNA expression and ER, PR content in 75 breast cancer. Formalin-fixed par affin-embedded tissue sections were used to preserve histological deta ils. IGF-II mRNA was evaluated by in situ hybridisation method and ER, PR by immunohistochemistry. IGF-II mRNA was scored semi-quantitativel y: 2.6% breast tumour specimen expressed no IGF-II mRNA, 46.7% had low levels of expression (16F-II -) and 50.7% had moderate or high IGF-II mRNA content (IGF-II +). IGF-II mRNA was found in the stroma fibrobla sts surrounding malignant lesions and no signal was detected in malign ant epithelial cells. In contrast, ER and PR were expressed only by ne oplastic epithelial cells and no immunoreactivity was found in the str oma: 50/75 (66.6%) breast cancer specimens were positive for ER (ER+) and 35 (46.6%) for PR (PR+). Both, IGF-II mRNA and PR were directly co rrelated with the stromal proliferation (p<0.05 and p<0.001, respectiv ely). No relationship was found between IGF-II RNA and ER. In contrast 24/35 (73.5%) PR breast cancer tissues were IGF-II+(p<0.01) and a str ong correlation was found between epithelial PR immunostaining and str omal IGF-II mRNA content (p<0.003). Our data indicate that in breast c ancer IGF-II mRNA is generally expressed by stromal cells and ER and P R by ephitelial cancer cells, and that IGF-II mRNA expression is stron gly related with both percentage and staining intensity of PR+ epithel ial cancer cells. These data support the hypothesis that IGF-II produc ed by the fibroblasts may exert a paracrin effect on malignant epithel ium regulating its differentiation. (C) 1998, Editrice Kurtis.