title: Protein Expression for Novel Prognostic Markers (Cyclins D1, D2, D3, B1, B2, ITGβ7, FGFR3, PAX5) Correlate With Previously Reported Gene Expression Profile Patterns in Plasma Cell Myeloma.
abstract: 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.
authors.affiliation: Department of Pathology & Laboratory Medicine, Division of Hematology and Transfusion Medicine, University of Calgary/Calgary Laboratory Services (CLS), Calgary, AB, Canada.
authors.forename: Adnan
authors.initials: A
authors.lastname: Mansoor
authors.forename: Ariz
authors.initials: A
authors.lastname: Akhter
authors.forename: Payam
authors.initials: P
authors.lastname: Pournazari
authors.forename: Etienne
authors.initials: E
authors.lastname: Mahe
authors.forename: Sami
authors.initials: S
authors.lastname: Shariff
authors.forename: Fahad
authors.initials: F
authors.lastname: Farooq
authors.forename: Ghaleb
authors.initials: G
authors.lastname: Elyamany
authors.forename: Meer-Taher
authors.initials: MT
authors.lastname: Shahbani-Rad
authors.forename: Fariborz
authors.initials: F
authors.lastname: Rashid-Kolvear
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000235:genetics*; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D056765:Cyclin B2 / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics*; D056742:Cyclin D2 / Q000235:genetics; D056743:Cyclin D3 / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D039641:Integrin beta Chains / Q000235:genetics; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C503758:CCNB2 protein, human; C530104:CCND1 protein, human; C080336:CCND2 protein, human; C534696:CCND3 protein, human; D056765:Cyclin B2; D056742:Cyclin D2; D056743:Cyclin D3; D039641:Integrin beta Chains; C091368:integrin beta7; D019938:Cyclin D1; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3