High Oct-2 Protein Expression Is Associated with Decreased Overall Survival, While High Bob-1 Protein Expression Is Associated with Improved Overall Survival in Myeloma Patients.

Oct-2 and Bob1 are B-lymphoid lineage specific transcription factors which drive the expression of genes involved in B-lymphocyte and plasma cell development and differentiation, including the immunoglobulin heavy chain (IgH) genes and many others. It is also thought that these transcription factors drive the overexpression of oncogenes involved in IgH translocations through upregulation of the IgH enhancers. We sought to evaluate the expression of Oct-2 and Bob1 in multiple myeloma, a malignancy of the B cell/plasmacyte lineage, in order to determine their potential biological significance as determinants of disease behaviour/prognosis and as potential therapeutic targets.

A tissue microarray containing triplicate samples from 220 myeloma patient samples was generated. Samples were collected at the time of diagnosis between 1993 and 2008. To measure Oct-2 and Bob-1 protein expression in the CD138+ plasma cells of each sample, fluorescent immunohistochemistry was used to stain the samples and the HistoRx PM-2000 platformTM was used to generate an AQUA score for each patient. Oct-2 AQUA scores were available for 169 patient samples and Bob-1 AQUA scores were available for 169 patient samples. The analysis was repeated using conventional immunohistochemistry and visual scoring of staining intensity.

The Oct-2 and Bob-1 AQUA scores were continuously distributed over the patient cohort; thus, subsequent analyses were done by dividing the patient cohort by the median Oct-2 or Bob-1 AQUA score and comparing the group with high AQUA scores to the group with low AQUA scores. The patient group with high Oct-2 AQUA scores had an OS of 52.8 months compared to 73.1 months in the group with low Oct-2 AQUA scores (hazard ratio [HR]=1.74, 95% confidence interval [CI]=1.11-2.73, p=0.0164). The patient group with high Bob-1 AQUA scores had an OS of 70.5 months compared with 38.3 months in the group with low Bob-1 AQUA scores (HR=0.46, 95% CI=0.29-0.71, p=0.0008). In a Cox regression proportional hazards model including autologous stem cell transplant (ASCT) status, serum albumin, serum β2-microglobulin and Oct-2 or Bob-1 AQUA scores, only ASCT status was independently predictive of OS. The patient group with low Oct-2 AQUA scores had a significantly higher proportion of ASCT recipients than the group with high Oct-2 AQUA scores. Conversely, the patient group with high Bob-1 AQUA scores had a significantly higher proportion of ASCT recipients than the group with low Bob-1 AQUA scores. Results were similar but not statistically significant when analyzing the TMA with conventional immunohistochemistry and visual scoring of staining intensity.

In this retrospective study high Oct-2 expression was found to be associated with decreased OS, while high Bob-1 protein expression was associated with increased OS. These results suggest that Oct-2 is a negative prognostic factor in myeloma, while Bob-1 is a favorable prognostic factor, and demonstrates the applicability of the HistoRx platform to myeloma bone marrow TMA analysis. Since this was a small, exploratory study these results must be interpreted with caution and must be confirmed in a larger, prospective analysis.

No relevant conflicts of interest to declare.