Gelatinase A/TIMP-2 imbalance in lymph-node-positive breast carcinomas, as measured by RT-PCR.
Over-production of gelatinase A (MMP-2) or under-production of its inhibitor (TIMP-2) may result in the matrix degradation crucial for metastasis, and early evaluation of their expression in primary tumor would offer important prognostic informations. RT-PCR amplicons of MMP-2 and TIMP-2 mRNA from tissue biopsies of 13 breast carcinomas and one fibrocystic mastopathy were quantitated. In comparison with their normal-tissue counterparts, their expression trends were not uniform: in some cases MMP-2 increased in the tumor without changes in TIMP-2, in others TIMP-2 expression also increased, although to a lesser extent than MMP-2; only in 2 cases was it slightly lower in the tumor tissue. Nevertheless, clearer insights were gained from the comparison of the ratio (R) between MMP-2tumor/normal and TIMP-2tumor/normal: as in the fibrocystic mastopathy, the R in carcinomas without lymph-node involvement (LN-) was usually lower than I in most cases. In contrast, in 5 out of 6 patients with lymph-node metastasis (LN+), the ratio ranged between 2 and 4. While the R magnitude was not related to the frequency of positive lymph nodes out of the total analyzed, nor to relapse status at follow-up (all relapse-free), the clear-cut difference between the LN- and LN+ groups was statistically significant. Results suggest that evaluation of MMP-2/TIMP-2 mRNA balance may constitute an early prognostic approach, which may also be more reliable concerning cancer aggressiveness as compared with the MMP-2 alone, and that boosting TIMP-2 expression may be a therapeutic strategy to prevent metastasis.
Onisto
M
M
Institute of Histology and General Embryology, Medical School, University of Padua, Italy.
Riccio
M P
MP
Scannapieco
P
P
Caenazzo
C
C
Griggio
L
L
Spina
M
M
Stetler-Stevenson
W G
WG
Garbisa
S
S
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D018093:Gelatinases / Q000032:analysis*; D015870:Gene Expression; D006801:Humans; D008207:Lymphatic Metastasis; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000032:analysis*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2; D014158:Transcription, Genetic
D011506:Proteins; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2