Abstract
To the Editor,
I read with great interest the recent article by Reis et al (1). TIMP-1 is emerging as an important prognostic indicator and marker of systemic malignancies besides prostate carcinomas.
Breast cancers that show increased levels of TIMP-1 are comparatively more resistant to chemotherapeutic agents such as paclitaxel (2). As a result, patients with high TIMP-1 levels have significantly worse 5-year overall survival than patients with low expression of TIMP-1. A similar relationship is seen between disease-free survival and TIMP-1 in breast cancer patients. For instance, in one study the 10-year overall survival rate in patients with TIMP-1-negative breast cancers was 28% higher than that in patients with TIMP-1-positive breast cancers (3). Hence, in conjunction with nodal status, TIMP-1 may actually improve the stratification of clinical outcome and prognosis in breast cancer patients (4).
The metastatic potential in pulmonary carcinomas is influenced by serum TIMP-1 levels (5), as is the response to chemotherapeutic agents. Highest tissue TIMP-1 levels are usually seen in lung cancer patients with concomitant tobacco use and are typically associated with an adverse prognosis (6). Interestingly, upregulation of TIMP-1 secondary to administration of agents such as atorvastatin increases the sensitivity of non-small cell pulmonary cancers to chemotherapeutic agents such as carboplatin (7). The invasive potential of estrogen-receptor-positive non-small cell lung carcinomas is attenuated by the administration of tamoxifen as a result of its negative impact on the MMP-9/TIMP-1 ratio (8). Increased expression of TIMP-1 is also seen in gastric malignancies. In fact, there is a close relationship between clinical stage, liver metastasis and depth of invasion in gastric carcinomas and serum TIMP-1 levels (9).
The above examples clearly illustrate the significance of assessing serum TIMP-1 levels in systemic malignancies.