Angiogenesis extent and expression of matrix metalloproteinase-2 and -9 correlate with upgrading and myometrial invasion in endometrial carcinoma.
BACKGROUND
Changes in angiogenesis and expression of extracellular matrix-degrading enzymes have been substantiated during tumour changeover and progression.


METHODS
Tissues from 64 biopsies of endometrial carcinoma (EC) and 15 biopsies of normal (control) endometrium were investigated immunohistochemically to determine their microvessel number, and by in situ hybridisation to determine the expression of mRNA of the matrix metalloproteinase-2 (MMP-2, gelatinase A) and metalloproteinase-9 (MMP-9 gelatinase B). EC were grouped according to both histological grade (G) G1 to G3 and depth of myometrial (M) invasion M1 to M3.


RESULTS
EC as a whole gave significantly higher counts over control endometria. Counts of the G1 group overlapped those of the control group, increased significantly in the G2 and even more in the G3 group. G3 biopsies in particular also displayed most microvessels widely scattered in the tumour tissue, in close association with tumour cells, and as winding and arborized tubes, often dilated in microaneurysmatic segments. Counts also increased in M2 and M3. Expression of the MMP-2 and MMP-9 mRNA, evaluated as percentages of positive biopsies and intensity of expression, were upregulated with the transition from control and G1 groups to G2 and G3, and in relation to advancing depth of invasion. In EC, MMP-2 and MMP-9 mRNA were also expressed by host stromal cells, including microvascular endothelial cells, fibroblasts and macrophages. In the control biopsies, poor expression of MMP-2 mRNA in few endothelial cells and no expression of MMP-9 mRNA were detected.


CONCLUSIONS
These in situ data suggest that angiogenesis and degradation of extracellular matrix occur simultaneously with EC upgrading and advancing depth of invasion, and that EC cells and some host stromal cell populations cooperate in tumour progression.
Iurlaro
M
M
Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Italy.
Loverro
G
G
Vacca
A
A
Cormio
G
G
Ribatti
D
D
Minischetti
M
M
Ria
R
R
Bruno
M
M
Selvaggi
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002277:Carcinoma / Q000098:blood supply* / Q000473:pathology / Q000601:surgery; D017364:Collagenases / Q000235:genetics / Q000302:isolation & purification; D016889:Endometrial Neoplasms / Q000098:blood supply* / Q000473:pathology / Q000601:surgery; D010450:Endopeptidases / Q000235:genetics / Q000302:isolation & purification*; D005260:Female; D018093:Gelatinases / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D017403:In Situ Hybridization; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000235:genetics / Q000302:isolation & purification; D008875:Middle Aged; D009215:Myometrium / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000302:isolation & purification
D012333:RNA, Messenger; D010450:Endopeptidases; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9