Abstract PS16-26: The prognostic role of MMP 9 in early breast cancer
Authors: Michal Mego, Zuzana Cierna, Marian Karaba, Gabriel Minarik, Juraj Benca, Tatiana Sedlackova, Ivana Mrvova, Daniel Pindak, Katarina Rejlekova, Jozef Mardiak, Katarina Kalavska
Journal: Cancer Research (2021)

Abstract Background: Matrix metalloproteinase 9 (MMP9) is involved in the extracellular matrix degradation during physiological and pathological conditions including tumorigenesis. This translational study was aimed to evaluate the prognostic role of the intratumoral MMP9 expression and correlate it with presence of CTCs in early breast cancer. Methods: A total of 318 primary breast cancer (PBC) patients were enrolled into this study. Surgical specimens were processed by the tissue microarray method and subjected to immunohistochemistry using the MMP9 monoclonal antibody. The MMP9 expression was evaluated in tumor cell as well as in tumor associated stroma. Quantitative real-time polymerase chain reaction -based assays was applied for identification of CTCs. Results: Significantly increased expression of MMP9 was found in breast cancer cells when compared to tumor associated stroma. A positive correlation was determined between MMP9 expression and hormone positive status as well as low proliferation index of analysed breast cancer tumour cells. Additionally, in tumor associated stroma was confirmed only the association with hormone receptor status. The univariate survival analysis of whole tested population detected no prognostic role of MMP9 expression neither in tumor cells (HR = 0.96, 95% CI 0.58-1.59, P = 0.864) nor in tumor associated stroma (HR = 1.29, 95% CI 0.60-2.78, P = 0.547). However, the subgroup of in hormone receptor negative and triple negative patients with absence of MMP9 expression in tumor cells and stroma had significantly better disease-free survival (DFS) (HR = 0.33, 95% CI 0.12-0.93, P = 0.025, and (HR = 0.14, 95% CI 0.00-4.81, P = 0.002, respectively) and (HR = 0.17, 95% CI 0.05-0.57, P = 0.003); (HR = 0.12, 95% CI 0.00-4.89, P = 0.001) compared with patients with presence of MMP9. Moreover, while tumor MMP9 was prognostic in CTC_EMT positive subgroup (HR = 0.40, 95% CI 0.16-0.95, P = 0.047), absence of stromal MMP9 had protective role in CTC_EP positive patients (HR = 0.18, 95% CI 0.01-2.75, P = 0.053). Conclusions: Our data suggest that the increased expression of MMP9 in PBC was related with favorable tumor characteristics. However, it´s prognostic value was limited only to hormone receptor negative, triple negative, CTC_EMT and CTC_EP positive subgroups. Therefore, we can suppose that evaluating of MMP9 tumor expression could help identify patients with increased risk of disease recurrence in these subgroups of patients. Citation Format: Michal Mego, Zuzana Cierna, Marian Karaba, Gabriel Minarik, Juraj Benca, Tatiana Sedlackova, Ivana Mrvova, Daniel Pindak, Katarina Rejlekova, Jozef Mardiak, Katarina Kalavska. The prognostic role of MMP 9 in early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-26.