Cost-Effective, User-Friendly Proliferation and Cytogenetic Analysis in Myeloma
Scott Ely, Alvin Modin, Adriana Rossi, Olivier Elemento, Solomon Shenker. Weill-Cornell Medical Center, New York, NY
Background: Myeloma prognosis is predicted by proliferation and cytogenetics. Data suggest that therapeutic decisions should incorporate these factors. For technical reasons, proliferation analysis is not available in clinical labs and false negatives are common with FISH. We developed a method to assess proliferation and the commonest cytogenetic abnormalities using standard IHC equipment.
Design: In an IRB-approved trial, 104 marrow biopsies were immunostained for MUM1 (red) and Ki67 (blue) without counterstain.
The same IHC was performed substituting cyclin D1 for Ki67. A test set showed 100% concordance between strong/uniform D1 and t(11;14) and weak/partial D1 with hyperdiploidy. Standard FISH was performed. Proliferation was assessed by manual count, using commercially available image analysis (IA) hardware, and also using standard photomicrographs with our own software.
Results: 23/104 (22%) biopsies showed strong, uniform D1 and MUM1; 16/23 (69%) had t(11;14). 44/104 (42%) showed weak, partial D1; 82% (36/44) had hyperdiploidy. Analysis of Ki67/MUM1, comparing pre-therapy biopsies to biopsies taken after 8 days of therapy showed an average decreased of 94.6%. In comparison to manual counting, the commercial IA system data varied +19% to (-)23%, while our software varied only +12% to (-)9%.
Conclusions: Our method enabled assessment of efficacy by day 8 of therapy, much sooner than any other means. It has greater sensitivity for detecting t(11;14) and hyperdiploidy than FISH. Our software works on any computer for IA using jpg's taken with any standard microscope and camera.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 224, Wednesday Afternoon