High tissue inhibitor of matrix-metalloproteinase 2 expression correlates with poor prognosis in breast cancer

Heyman, Thomas; Joseph, Chitra; Craze, Madeleine; Green, Andrew; Nolan, Chris; Rueda, Oscar; Provenzano, Elena; Rakha, Emad; Ellis, Ian O; Mukherjee, Abhik

Abstract

Background & objectives
TIMP2, tissue inhibitor of matrix-metalloproteinase 2, inhibits the matrix-metalloproteinase, MMP2, but may activate pro-MMP2. Hence its correlation with prognosis in breast cancer (BC) is contradictory. This study investigated the correlations of TIMP2 expression in BC with clinicopathological variables.
Methods
Differential expression analysis of TIMP2 was assessed in the lymphovascular invasion (LVI) positive versus negative cohorts in the METABRIC BC dataset. Immunohistochemical analysis for TIMP2 (1:50 dilution) expression was conducted on BC tissue microarrays (n=1048) and clinicopathological correlations were assessed, including VI and expression of MMPs, 2, 14 and 15.
Results
TIMP2 was associated with positive LVI in the METABRIC cohort (p= 0.002). On immunohistochemistry, significant positive correlations were found between TIMP2 protein expression and higher grade (p=0.019), including its components nuclear pleomorphism (p=0.004), mitotic count (p=0.000087), LVI (p=0.014) and Nottingham prognostic Index (p=0.024). TIMP2 expression showed a significant correlation with negative ER status (0.014) and Triple negative status (p =0.008). TIMP2 expression also showed a positive correlation with cytoplasmic MMP2, MMP14 and MMP15 (p

• Conference Name: 32nd Congress of the ESP and XXXIII International Congress of the IAP
• Conference Location: Glasgow, UK (virtual)
• Start Date: Dec 6, 2020
• End Date: Dec 8, 2020
• Acceptance Date: May 27, 2020
• Online Publication Date: Dec 8, 2020
• Publication Date: Dec 8, 2020
• Deposit Date: Aug 27, 2020
• Publicly Available Date: Dec 8, 2020
• Volume: 477, Supplement 1
• Pages: S52
• Series Title: European Journal of Pathology
• Series ISSN: 1432-2307
• Chapter Number: PS-01-043
• Public URL: https://nottingham-repository.worktribe.com/output/4854818
• Related Public URLs: https://www.esp-congress.org/