High Intratumoral Galectin-1 Is Associated with Adverse Outcome in ALK-Negative, CD30-Positive Peripheral T-Cell Lymphomas

Galectin-1 (Gal-1) has been associated with prognosis in several cancers including lymphomas. CD30-dependent cell signaling mediated by Gal-1 has been proposed in CD30-positive lymphomas and cell lines. Still, Gal-1 expression has not been systematically assessed as a possible prognosticator in nodal peripheral T-cell lymphomas (PTCL).

Tissue micro arrays with pre-therapeutic tumor specimens from 169 patients with nodal PTCL (n=29 AITL, n=37 ALK-negative ALCL, n=14 ALK-positive ALCL, and n=83 PTCL-NOS) were assessed for intratumoral Gal-1 expression by immunohistochemistry and quantified using digital image analysis. For outcome analysis Gal-1 expression in tumors was categorized in two groups i.e. i) the quartile of patients with highest expression values (Gal-1 high) and ii) the lower three quartiles taken as one group (Gal-1 low). Overall survival (OS) in high and low Gal-1 groups was compared in the entire cohort and in CD30-positive subsets of PTCL.

Gal-1 stains were evaluable in 163 cases (96%). The Gal-1 expression level was significantly different between PTCL subtypes (P<0.001) with ALK-positive and ALK-negative ALCL having the highest levels. Moreover, CD30-positive PTCLs showed higher expression compared with CD30-negative ones (P=0.001). No significant difference in OS according to Gal-1 expression was seen in the PTCL cohort as a whole or in the CD30-positive subgroup when including ALK-positive ALCL. Due to the superior survival and very few events among ALK-positive ALCL patients (P<0.001), a CD30-positive cohort without ALK-positive ALCL was analyzed separately. This cohort consisted of ALK-negative ALCL (n=37), PTCL-NOS (n=5), and AITL (n=1). Within this cohort, patients with 'Gal-1 high' had significantly poorer outcome (5 yrs OS 10%, 95% confidence interval (CI): 0.1-36) than their 'Gal-1 low' counterparts (5 yrs OS 48%, 95%CI: 30-64, P=0.025). Risk factors were evenly distributed between the groups. In univariate analyses age≤60, normal LDH, and performance score <2 correlated with superior survival, whereas high Gal-1 expression significantly predicted adverse outcome at both univariate (HR 2.4, 95%CI: 1,1-5.5, P=0.030) and multivariate level (HR 2.9, 95%CI: 1.1-7.8, P=0.027). We conclude that high intratumoral Gal-1 expression correlates with inferior survival in nodal ALK-negative, CD30-positive PTCL patients.