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.


METHODS
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.
Jussila
Tommi
T
Department of Pathology, University of Oulu, P.O. Box 5000 FIN-90014, Kajaanintie 52, 90220 Oulu, Finland.
Kauppila
Saila
S
Bode
Michaela
M
Tapanainen
Juha
J
Risteli
Juha
J
Risteli
Leila
L
Kauppila
Antti
A
Stenbäck
Frej
F
D000230:Adenocarcinoma / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024042:Collagen Type I / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D024061:Collagen Type III / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D016889:Endometrial Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000737:chemistry / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D010455:Peptides; D011347:Procollagen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis
D024042:Collagen Type I; D024061:Collagen Type III; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D012333:RNA, Messenger; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; C041876:procollagen Type III-N-terminal peptide