Expression of heat shock proteins in classical Hodgkin lymphoma: correlation with apoptotic pathways and prognostic significance

Aims: Heat shock proteins (HSPs), known to inhibit apoptosis and promote cellular survival, are overexpressed in many tumours. We analysed the expression of relevant HSPs and heat shock factor 1 (HSF1) in classical Hodgkin lymphoma (cHL) and their relationship with caspase signalling pathways and patient outcome. Methods and results: Using tissue microarrays (TMAs), most cases showed strong immunohistochemical expression of HSPs [10, 27, 40, 60, 70, 90, 110, HO1, cell division cycle 37 homolog (CDC37) and HSF1, which points to cHL as a potential candidate to stress-response inhibitors. Active caspases 3, 8 and 9 were detected in 55.1%, 55.4% and 96.2% of cases although cleaved poly (ADP-ribose) polymerase (PARP) was observed in only 16.1%, suggesting an improper functioning of apoptosis. Statistical analysis showed associations of HSP70 with active caspase 3 (P = 0.000); HSP40 with active caspase 9 (P = 0.031) and p53 (P = 0.003); HO1 with p53 (P = 0.006) and p21 (P = 0.005); and p53 with p21 (P = 0.015). Conclusions: Correlations between the expression of apoptotic markers and HSPs may suggest a role for the latter in modulating apoptosis in cHL, mainly through the HSP70-HSP40 system, and in the stabilization of p53. Survival analyses showed that absence of active caspase 8 and HO1 had a negative impact in patient outcome.