Examining Measures of Proliferation for Use in Risk Stratification of Myeloma

Abstract 5093

A relative increase in proliferation is now accepted as the most important measure in risk stratification of myeloma.

Attempts to include measures of proliferation in different stratification strategies have been met with obstacles largely influenced by their practicality and economic viability in the clinical setting.

The plasma cell labelling index (PCLI) is the gold standard used in myeloma; however it is still only used in a minority of centers across the globe. New surrogate markers of proliferation, such as serum biomarkers and transcription-based methods, are under investigation but few have evolved to become part of a uniform strategy in the stratification of myeloma. The gene-expression based proliferation indices (gPI) described by Bergsagel et al, Shaughnessy et al and Hose et al all show similar correlation with PCLI. Studies comparing all currently available methods are lacking.

In a cohort of 70 patients, PCLI and gPI were compared with two immunohistochemistry-based methods of measuring proliferation, Ki67 and a more specific measure of S-phase entry – phosphorylation of minichromosome maintenance protein 2 (pMcm2) at serine 40/41, combined with dual staining of CD138. We observed a similar correlation of gPI wth PCLI to that previously reported (r value; CI – 0.43;0.21–0.61). Both Ki67 and pMcm2 staining showed a stronger correlation with PCLI than with gPI and PCLI (r value; CI – 0.81;0.71–0.88 and 0.86; 0.78 – 0.91 respectively).

PCLI and gPI have already been shown to be an independent predictor of time to progression and overall survival. Although this sample size was too small to test for time to progression or overall survival and thus independence, a logical extrapolation would indicate similar independence and predictions on survival and time to progression.

As Ki67 is routinely used for more proliferative cancers in the clinic, the extension of its use as part of a new stratification system in myeloma provides interesting possibilities for further exploration.