Expression of heat-shock protein-90 in non-Hodgkin's lymphomas

Heat- shock protein- 90 ( HSP90) inhibitors are currently being used in phase I clinical trials for treating patients with a variety of neoplasms including lymphomas. Using immunohistochemical methods, we assessed for HSP90 expression in 412 cases of non- Hodgkin's lymphoma. In B- cell lymphomas, HSP90 was moderately to strongly expressed in all cases of Burkitt's lymphoma ( 5/ 5, 100%), and in subsets of follicular lymphoma ( 17/ 28, 61%), diffuse large B- cell lymphoma ( 27/ 46, 59%), nodal marginal zone B- cell lymphoma ( 6/ 16, 38%), plasma cell neoplasms ( 14/ 39, 36%), small lymphocytic lymphoma/ chronic lymphocytic leukemia ( 3/ 9, 33%), mantle cell lymphoma ( 12/ 38, 32%) and lymphoplasmacytic lymphoma/ Waldenstrom macroglobulinemia ( 3/ 10, 30%). HSP90 was weakly expressed in six of 14 ( 43%) cases of extranodal marginal zone B- cell lymphoma of mucosa-associated lymphoid tissue. In T- cell lymphomas, HSP90 was moderately to strongly expressed in subsets of anaplastic large- cell lymphoma ( 14/ 24, 58%; 9/ 12 ALK + and 5/ 12 ALK -), precursor- T- cell lymphoblastic leukemia/ lymphoma ( 20/ 65, 31%), unspecified peripheral T- cell lymphoma ( 8/ 43, 23%) and angioimmunoblastic T- cell lymphoma ( 2/ 17, 12%). HSP90 was weakly expressed in seven of 58 ( 12%) cases of mycosis fungoides. We conclude that HSP90 is commonly expressed in a subset of many types of B- and T- cell lymphoma. These data suggest that many lymphoma types are suitable targets for modulation of HSP90 activity, and that HSP90 inhibitors are a potential investigational therapy for lymphoma patients.