Prognosis of gastric carcinoma revealed by interactions between tumor cells and basement membrane.
The extra-cellular matrix (ECM) related antigens, type IV collagen, laminin, M(r) 68,000 laminin receptor (LR), M(r) 72,000 type IV collagenase (MMP-2), its inhibitor TIMP-2, and alpha 2-macroglobulin expression have been immunohistochemically investigated in 100 cases of human gastric carcinoma with a 5-yr follow up. Basement membranes were inversely related to tumoral differentiation. At the early intramucosal stage of both intestinal and diffuse histological types, TIMP-2 was expressed by the majority of tumor cells (60/63%), whereas MMP-2+ and LR+ cells were in the minority (24/19%, 23/0%, respectively). At the early submucosal stage, TIMP-2+ cells moderately decreased in both histological types (49/49%), whereas a consistently higher number of both MMP-2+ and LR+ cells were detected only in the diffuse carcinomas (72%). In the advanced stage, the expression of TIMP-2 further declined (22/24%), although the other two antigens increased or maintained high levels of expression. AMG+ cells never exceeded 10% in either histological type at any stage. In the liver metastases, both MMP-2+ and LR+ cells were more numerous than in the primary tumor (P < 0.002 and P < 0.01). Patients who died from their primary tumor had higher percentages of LR+, MMP-2+, and AMG+ cells and lower percentages of TIMP-2+ cells with respect to survivors. We believe evaluation of ECM-related antigens, and especially TIMP-2, may help determine a confident prognosis for gastric cancer.
Grigioni
W F
WF
Pathology Institute, Medical School of Bologna, Italy.
D'Errico
A
A
Fortunato
C
C
Fiorentino
M
M
Mancini
A M
AM
Stetler-Stevenson
W G
WG
Sobel
M E
ME
Liotta
L A
LA
Onisto
M
M
Garbisa
S
S
D000970:Antineoplastic Agents / Q000378:metabolism; D001485:Basement Membrane; D014408:Biomarkers, Tumor; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005500:Follow-Up Studies; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D017474:Receptors, Laminin / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D019716:Tissue Inhibitor of Metalloproteinase-2
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016326:Extracellular Matrix Proteins; D011506:Proteins; D017474:Receptors, Laminin; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2