CD68, CD163, and matrix metalloproteinase 9 (MMP-9) in breast tumor microenvironment to predict breast cancer survival: are they enough?

Sara BravacciniEmail author View ORCID ID profile and
Roberta Maltoni

Breast Cancer Research201921:49

https://doi.org/10.1186/s13058-019-1134-z

Published: 3 April 2019

The original article was published in Breast Cancer Research 2018 20:154

Keywords

CD68
CD163
Matrix metalloproteinase 9
Breast cancer
Prognosis

Pelekanou and colleagues recently evaluated tumor-associated macrophage (TAM) biomarkers (CD68, CD163) and MMP-9 expression in breast cancer (BC) and their role in identifying subclasses of patients who can benefit from TAM-targeting therapies [1]. The authors concluded that the association between high co-expression and co-localization of MMP-9/CD163/CD68 and poor survival in ER+ cancers suggests that these patients may be candidates for macrophage-targeted therapies. We found the paper very interesting but would like to make some comments. Using an in situ approach, Pelekanou and colleagues found that CD68 only correlated with poor survival in ER− patients. They used multivariate analysis to evaluate overall survival. However, apart from age, tumor size, and grade, other validated clinical pathological characteristics that can impact prognosis were not included in the multivariate analysis, e.g., the presence and number of involved lymph nodes, Her 2 status, proliferative activity of the primary tumor, and PAM50 subtype classification. In other words, the poorer prognosis seen in ER− patients may have been due to the presence of other unfavorable clinical pathological characteristics that negatively influence prognosis. The authors did not explain the cutoff they used to define PgR positivity, an important aspect given that the prognostic importance of PgR has been demonstrated in some BC patient subsets [2].