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

Almudena Santón (1) , Monica Garcia-Cosio (2) , Eva Cristobal (2) , Alejandro Pascual (2) , Alfonso Muriel (3) , José García-Laraña (4)

1 Pathology
2 Pathology
3 Biostatistics
4 Haematology

Aims: Heat shock proteins (HSPs), which are known to inhibit apoptosis and promote cellular survival, are over-expressed in many tumours. We analyzed 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, most cases showed strong immunohistochemical expression of HSPs (10, 27, 40, 60, 70, 90, 110, HO1, 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; however, cleaved PARP was observed only in 16.1%, suggesting 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.

Mots clés: Medicine

Almudena Santón, Monica Garcia-Cosio, Eva Cristobal, Alejandro Pascual, Alfonso Muriel, et al.. Expression of heat shock proteins in classical Hodgkin lymphoma: correlation with apoptotic pathways and prognostic significance. Histopathology, 2011, 58 (7), pp.1072. ⟨10.1111/j.1365-2559.2011.03803.x⟩. ⟨hal-00631271⟩