Characterization of type I collagen synthesis and maturation in uterine carcinosarcomas

BACKGROUND. Epithelial malignancies often induce an enhanced expression of interstitial collagens in the fibroblasts within the tumor tissue and the s urrounding non-neoplastic stroma. In uterine carcinosarcomas (malignant mix ed mullerian tumors [MMMTs]) both the stroma and the epithelium are maligna nt. METHODS. In this investigation, both in situ hybridization and immunohistoc hemical staining were applied with two different antibodies that were capab le of distinguishing between newly synthesized and mature, trivalently cros s-linked Type I collagen to define Type I procollagen mRNA expression and t he synthesis and maturation of the corresponding protein in MMMTs. RESULTS. In the better differentiated parts of these tumors, in which antic ytokeratins stained only clearly carcinomatous cells, Type I procollagen mR NA expression was limited to stromal fibroblasts; mature Type I collagen bu ndles were abundant and regular. In poorly differentiated areas, in which a nticytokeratins stained only a few individual cells, Type I procollagen mRN A was expressed peculiarly by three morphologically different cell types. I n addition to benign mesenchymal cells, Type I procollagen mRNA was present in atypical epithelial and mesenchymal cells. In these tumors, the collage n bundles close to the malignant cells were comprised of newly synthesized Type I collagen, with only little evidence of the presence of mature, fully cross-linked collagen. CONCLUSIONS. These results strongly suggest that the undifferentiated cells of MMMTs are capable of producing their own stroma with irregularly arrang ed collagen bundles. Cancer 1999;86:1299-306. (C) 1999 American Cancer Soci ety.