Among
plasma cell myeloma (PCM) patients, gene expression profiling (GEP)-based molecular classification has proven to be an independent predictor of survival, after autologous
stem cell transplantation. However, GEP has limited routine clinical applicability given its complex methodology, high cost, and limited availability in clinical laboratories. In this study, we have evaluated
biomarkers identified from GEP discoveries, utilizing immunohistochemistry (IHC) platform in a cohort of PCM patients. IHC staining for
cyclins B1, B2, D1, D2, D3, FGFR3, PAX5, and
integrin β7 (ITGβ7) was performed on the bone marrow biopsies of 93 newly diagnosed PCM patients. Expression of FGFR3 was noted in 10 (11%) samples correlating completely with t(4;14)(p16;q32) results (P<0.001); however, the association between FGFR3 and
cyclin D2 expression was not significant (P=0.14). ITGβ7 expression was present in 9/93 (9%) patients and all these samples also demonstrated upregulated expression of
cyclin D2 (P=0.014). Expression of
cyclins D1, D2, and D3 was variable in this cohort. Positive
protein expression of
cyclin D1 was noted in 30/93 (32%), D2 in 17/93 (18%), and D3 in 5/93 (5%) samples. Coexpression of
cyclins D1 and D2 was observed in 13/93 (14%) samples, whereas 28 (30%) samples were negative for all the 3
cyclin D proteins.
Cyclin B1 was not expressed in any sample, despite adequate staining in positive controls.
Cyclin B2 was expressed in 33/93 (35%) and PAX5
protein was noted in 7/93 (8%) samples. In summary, we have demonstrated that
mRNA-based prognostic markers can be detected by routine IHC in decalcified bone marrow samples. This approach may provide a useful tool for the wider adoption of prognostic makers for risk stratification of PCM patients. We anticipate that such an approach might allow patients with high-risk immunoprofiles to be considered for other potential novel therapeutic agents, potentially sparing some patients the toxicity of stem cell transplant.