Abstract
Abstract 5019
Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous category and tremendous effort has been made to identify sub-groups that are prognostically significant and to guide therapeutic decisions. Aldehyde dehydrogenase (ALDH) a family of ubiquitous enzymes throughout mammalian tissues catalyzes the oxidation of aldehydes to their corresponding carboxylic acids. Isoform 1 (ALDH1) plays a role in the biosynthesis of retinoic acid from Vitamin A. Retinoic acid is a regulator of cellular proliferation, differentiation and survival in normal human tissues. High expression of ALDH1 has been demonstrated in the putative cancer stem cells in malignancies of breast, lung, colon and other organs. Its expression has been associated with increased replicative potential, the ability to differentiate along multiple development lines, high tumorigenic potential and increased metastatic potential. However, more recently ALDH1 expression has been shown to correlate with favorable outcome in ovarian cancer. It has not been studied in DLBCL. The aim of the current study is to evaluate the expression of ALDH1 in DLBCL.
Formalin-fixed, paraffin embedded sections from 88 DLBCLs, were immunostained by automated methods (Ventana Medical Systems, Inc, Tucson, AZ) using monoclonal mouse anti-human ALDH antibody (Clone: 44/ALDH; Immunogen: Human ALDH1, aa 7 – 128; BD Transduction Laboratories). Cytoplasmic immunoreactivity was semi quantitatively assessed in all cases. Scoring was based on staining intensity (weak, moderate, intense) and percentage of positive cells (focal <= 25%, regional 26-50%, diffuse >50%).
were correlated with clinicopathologic variables.
High expression of ALDH1 was observed in 26/88 (30%) cases of DLBCL. The staining intensity and distribution pattern varied somewhat by outcome data. Remission status was known in 23 patients. 18 patients achieved complete remission. Interestingly, all 7 patients with high expression of ALDH1 achieved complete remission (p= 0.095). Recurrence information was known in 87 patients. High expression of ALDH1 was seen in 26 cases. Only one of these patients recurred (p=0.19). No association was seen with stage, HIV status, survival or age.
We have demonstrated that ALDH1 is expressed in DLBCL. Moreover, cases with high expression of ALDH1 trend towards complete remission and lack of recurrence. Further studies of ALDH1 expression in DLBCL appear warranted, potentially defining prognostically relevant sub-groups.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.