Alterations of basement membrane in di-isopropanolnitrosamine-induced carcinogenesis of the rat thyroid gland: an immunohistochemical study

Alterations of basement membrane (BM) in di-isopropanolnitrosamine (DIPN)-i nduced carcinogenesis of the rat thyroid gland were examined by means of im munohistochemical localization of collagen type TV (CN-IV), laminin (LN), a nd fibronectin (FN) in prenodular and nodular thyroid lesions, correlating with the morphogenesis and proliferative activity of these lesions. Adult m ale rats of the Wistar strain were injected s.c. in the back with DIPN, and the thyroid glands were removed at the 15th and 30th week of treatment. Ea ch of 133 thyroid lesions was histochemically analyzed. The follicular epit helial BM as revealed by CN-IV and LN was discontinued or completely lost d uring the progression of thyroid lesions from pre-nodular to nodular lesion s and finally overt carcinomas. At the same time, the BM of vascular endoth elial cells demonstrated a loss of dense capillary networks of follicles, a sinusoidal dilatation and, predominantly in carcinomas, development of int erstitial-type blood vessels. However, FN, which was hardly stained in the normal thyroid tissue, was remarkably deposited in the interstitium of inva sive carcinomas. These observations strongly suggested that alterations of BM structure play a key role in the morphogenesis of rat thyroid tumors, an d that the expression of FN is an important step in the invasive growth of thyroid tumors.