gelatinase A/TIMP‐2 imbalance in lymph‐node‐positive breast carcinomas, as measured by RT‐PCR

Abstract

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.

Small Integrin Binding Ligand N -Linked Glycoprotein Gene Family Expression in Different Cancers

“…The observed increase in MMP-2 expression observed in tumor samples is consistent with previous studies of breast (41,42), colon (43)(44)(45)(46)(47), stomach (48,49), lung (50 -53), rectal (43,54), and kidney cancer (55)(56)(57). Whereas a strong association of increased MMP-3 has been found in breast cancer (41, 58 -61), the increased expression levels observed in other tumor types are not as well supported by published literature.…”

Clinical role of MMP‐2/TIMP‐2 imbalance in hepatocellular carcinoma

“…In the human body, the expression of MMP-2 and TIMP-2 overlaps in the various different tissues and proteolysis occurs as a result of an imbalance between MMP-2 and TIMP-2 activity. 9,10 MMP-2 has been implicated in a number of situations such as development, morphogenesis and tumor progression, where remodeling of the tissue architecture and alteration of ECM turnover occur. [11][12][13][14] Several studies have reported that MMP-2 is up-regulated in the course of different malignancies and is involved in tumor metastasis.…”

The Local Immune Mechanisms Involved in the Formation of Endometriotic Lesions

“…It is well known that in urothelial cancer patients the mean MMP-2/TIMP-2 ratio in patients with recurrence is significantly higher than that in patients without recurrence and the disease-free survival of patients with high MMP-2/TIMP-2 ratio is extremely poor compared with that of patients with lower ratios (Gohji et al, 1996). It was demonstrated also that evaluation of MMP-2: TIMP-2 mRNA balance may constitute an early prognostic indicator of human cancer (Onisto et al, 1995). Evidently, the elevation of the balance of MMP-2 and TIMP-2 in endometriotic tissue results in increase of invasive potential of ectopic endometrium.…”