Overexpression of LC3A autophagy protein in follicular and diffuse large B-cell lymphomas.

BACKGROUND AND

OBJECTIVES

Autophagy is a self-degradation mechanism induced under stress conditions in all eukaryotic cells. Its activity in human lymphomas has not been studied as yet.

METHODS

In this study, the autophagic activity of lymphoid cells was investigated in follicular lymphomas (FL; 48 cases), diffuse large B-cell lymphomas (DLBCL; 78 cases), and in reactive follicular hyperplasias (41 cases), using the light chain 3A (LC3A) antibody and a standard immunohistochemical technique.

RESULTS

In all cases, the pattern of LC3A reactivity was uniformly diffuse cytoplasmic, but expressed more frequently in FLs (68.8%) than in DLBCLs (41%) (p=0.02), and much more commonly in DLBCLs than in reactive lymph nodes (24.3%) (p<0.006). Interestingly, FLs expressing LC3A in >10% of lymphoid cells (high reactivity) were associated with the hypoxia-related protein HIF1α and the enzyme of anaerobic metabolism lactate dehydrogenase LDH5 (p=0.004 and p=0.003, respectively). Such associations, however, were not a feature in DLBCLs of increased LC3A activity.

CONCLUSIONS

LC3A expression in FLs is hypoxia-induced, whereas its expression in DLBCLs may be regulated by other molecular mechanisms. The current study provides a tool for further assessment of autophagic activity in translational and autophagy targeting therapy studies.