The Expression of the RUVBL1 Component of the R2TP Complex Correlates with Poor Prognosis in DLBCL

Abstract

<b><i>Introduction:</i></b> Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of non-Hodgkin’s lymphoma (NHL) accounting for 30% of adult NHL worldwide and 50% in developing countries like India. DNA damage and Myc-induced transformation are well-known contributing factors towards development of DLBCL. A recently identified HSP90 co-chaperone complex R2TP has been shown to contribute towards DNA damage and Myc-induced transformation. This study aimed to analyse the immunohistochemical (IHC) expression of R2TP complex components RUVBL1, PIH1D1, and RPAP3 in DLBCL patients and correlate with prognosis. <b><i>Methods:</i></b> DLBCL (<i>n</i> = 54) histological slides were retrieved from archives, and detailed histomorphological and clinical features were noted. IHC staining of R2TP complex components RUVBL1, PIH1D1, and RPAP3 was performed on 54 cases (FFPE) of DLBCL. Expression data were correlated with survival and clinical features. <b><i>Results:</i></b> Out of the 54 DLBCL cases, 59.26% (<i>n</i> = 32) stained positive for RUVBL1. The RUVBL1 expression was associated with poor prognosis in both progression-free survival (PFS) (<i>p = 0.0146</i>) and overall survival (OS) (<i>p = 0.0328</i>). The expression was positively correlated with bone marrow involvement (<i>p = 0.0525</i>). The expression of PIH1D1 was observed in 68.51% (<i>n</i> = 32) of DLBCL cases, and positive correlation was observed with international prognostic index score (<i>p = 0.0246</i>); however, no correlation was observed with PFS or OS. Finally, RPAP3 was found immunopositive in only 1 case of DLBCL. <b><i>Conclusions:</i></b> Immunopositivity for RUVBL1 is associated with poor prognosis along with a higher relapse rate amongst the DLBCL patients. PIH1D1 immunopositivity correlated with a higher IPI score.