Synthesis and maturation of type I and type III collagens in endometrial adenocarcinoma.

OBJECTIVE: The structure and distribution of type I and type III collagens in the extracellular matrix of malignant endometrium was evaluated for their roles in the development and progression of this neoplasm. STUDY
DESIGN: Collagen synthesis and deposition in endometrial adenocarcinomas was determined by immunohistochemical analysis of type I and type III procollagen and verified by computer-assisted morphometry and in situ hybridization.
RESULTS: In the stroma of well-differentiated adenocarcinomas increased intracellular collagen synthesis was observed in fibroblastic cells as well as increased extracellular formation of newly synthesized type I and type III procollagen. Collagen maturation was also rapid. In moderately differentiated tumors, destruction and dissolution occurred around invading islets, concomitantly with decreased deposits of both collagens, despite increases in corresponding mRNAs. In poorly differentiated neoplasms, solid epithelial islets coexisted with sparse and distinctly collagen-positive stroma. Poorly differentiated neoplasms also contained tumor cells exhibiting intracellular collagen staining as well as in situ hybridization signals. In highly malignant papillary adenocarcinomas, the tumor cells induced distinctly increased collagen synthesis and deposition of newly synthesized collagen but not the mature cross-linked protein.
CONCLUSIONS: In malignancy, compression of surrounding stroma and a fibroproliferative response with increased collagen synthesis and deposition may prevent tumor growth. In more advanced lesions, stromal dissolution may permit tumor spread and in highly malignant lesions an abnormal stroma may promote neoplasm progression.