Ann Oncol. 2021 Aug 23:S0923-7534(21)04275-7. doi: 10.1016/j.annonc.2021.08.1991. Online ahead of print.
ABSTRACT
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease with respect to outcome. Features of the tumor microenvironment are associated with prognosis when assessed by gene expression profiling. However, it is uncertain whether assessment of the microenvironment can add prognostic information to the most relevant and clinically well-established molecular subgroups when analyzed by immunohistochemistry.
PATIENTS AND METHODS: We performed a histopathologic of biomarkers related to tumor microenvironment in a very large cohort (n=455) of DLBCL treated in prospective trials and correlated with clinic-pathologic and molecular data, including chromosomal rearrangements and gene expression profiles for cell-of-origin and tumor microenvironment.
RESULTS: The content of PD1+, FoxP3+ and CD8+, as well as vessel density, was not associated with outcome. However, we found a low content of CD68+ macrophages to be associated with inferior progression-free (PFS) and overall survival (OS) (p=0.023 and p=0.040, respectively) both at univariable and multivariable analysis, adjusted for the factors of the international prognostic index (IPI), MYC break and BCL2/MYC and BCL6/MYC double hit status. The subgroup of PDL1+ macrophages was not associated with survival. Instead, Secreted Protein Acidic And Cysteine Rich (SPARC)-positive macrophages were identified as the subtype of macrophages most associated with survival. SPARC-positive macrophages and stromal cells directly correlated with favorable PFS and OS (both, p[log rank] <0.001, p[trend]<0.001). The association of SPARC with prognosis was independent of the factors of the IPI, MYC double/triple hit status, Bcl2/c-myc double expression, cell of origin subtype and a recently published gene expression signature (LAMIS).
CONCLUSIONS: SPARC expression in the tumor microenvironment detected by a single immunohistochemical staining with fair-to-good inter-observer reproducibility is a powerful prognostic parameter. Thus, SPARC expression is a strong candidate for risk assessment in DLBCL in daily practice.
PMID:34438040 | DOI:10.1016/j.annonc.2021.08.1991
