Tumor Associated Macrophage Expression, CD163, Is Associated with Poorer Outcome in Diffuse Large B-Cell Lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma with various subtypes. Recent data of Tumor Associated Macrophages (TAM) in DLBCL have shown association with poor overall survival. We were interested in assessing these markers, in particular, for practical daily clinical use at a high volume cancer center. We therefore performed a retrospective study to evaluate expression of macrophage markers (CD68 and CD163) in DLBCL and determine overall survival (OS) and event free survival (EFS).

A total of 128 DLBCL cases were reviewed. Tissue microarrays (TMA) were constructed with cores in triplicate. CD163 and CD68 expression was assessed by immunohistochemistry (IHC) using anti-CD68 (KP-1, Ventana) and anti-CD163 (Vector Laboratories) performed on the automated Ventana XT platform according to manufacturer protocols (Tucson, AZ). The assessment of intratumoral CD163 infiltration was performed at objective magnification 40X by three observers (OB, HC and JTF) and a consensus was obtained. The number of CD163 macrophages was counted in three cores. The mean was calculated and the results were scored as follows: 0 (0 to 25 positive cells); 1 (between 26 to 50 positive cells); 2 (51 to 75 positive cells); 3 (76 to 100 positive cells). CD68 expression was assessed by IHC and the degree of intratumoral infiltration was scored as follows: 0 (less than 5% positive cells); 1 (between 5% to less than 50% of positive cells); 2 (more than 50% positive cells). Of 128 patients, 13 had limited clinical data, 23 were biopsies at relapse, and 92 were evaluable for OS and EFS from initial therapy. EFS was defined as progression of disease, secondary malignancy, or death due to disease or any other reason. OS was calculated from date of death or last follow-up date to date of diagnostic biopsy. EFS was calculated from event date or date of last follow-up to end of treatment date. SPSS software was used to calculate Kaplan Meier survival curves and statistics.

There were 51 (55%) males and 41 (45%) females (M:F ratio 1.2). The median age was 60 years (range from 10 to 90). A high number of tumor infiltrating CD163 expression (scores 0 [n=19], 1 [n=6], 2 [n=9] vs 3 [n=58]) was associated with significantly poorer OS (p=0.028) and EFS (p=0.005). A statistically significant difference was observed in patients with tumors that had abundant tumor associated macrophages with CD163 (score 3 >75 positive cells) on IHC. CD68 expression did not correlate with OS and EFS.

High CD163 expression is statistically significantly associated with decreased OS and EFS in DLBCL. Because of cleaner staining, scoring on a daily practical basis in a high volume center is useful. Our data supports initial few prior reports of this marker in DLBCL.

No relevant conflicts of interest to declare.