Association of tissue inhibitor of metalloproteinases-1 and Ki67 in estrogen receptor positive breast cancer

Abstract

Background: The role of tissue inhibitor of metalloproteinases-1 (TIMP-1) in estrogen receptor (ER) positive breast cancer remains to be fully elucidated. We evaluated TIMP-1 as a prognostic marker in patients treated with adjuvant tamoxifen and investigated TIMP-1s association with Ki67 and ER/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) profiles.

Material and methods: TIMP-1 expression was evaluated by immunohistochemistry (IHC) on formalin fixed paraffin embedded primary tumor tissue in two independent cohorts comprised of 236 and 192 patients, respectively.

Results: No differences in disease free survival (HR 0.98; 95% CI 0.63-1.53; p = 0.92) and overall survival (HR 0.94; 95% CI 0.63-1.43; p = 0.79) were observed according to TIMP-1 status. A significant negative association between TIMP-1 and Ki67 was identified (p = 0.015). TIMP-1 expression did not differ significantly according to ER/PR/HER2 profiles. When analyzed as separate variables PR and HER2 status tended to have a positive but non-significant association with TIMP-1 (PR: p = 0.08; OR 2.54; 95% CI 0.91-7.10, HER2: p = 0.08; OR 0.48; 95% CI 0.21-1.08) whereas ER status was not associated with TIMP-1 expression (p = 0.48; OR 0.68; 95% CI 0.23-1.99).

Conclusion: TIMP-1 does not appear to be prognostic in breast cancer patients receiving adjuvant tamoxifen. We identified a negative association between TIMP-1 and Ki67. We did not confirm our previous in vitro findings of a negative association between TIMP-1 and PR.