P53 Nuclear Expression Correlates with Hemizygous p53 Deletion and Has an Adverse Impact on the Outcome of Refractory/Relapsed Multiple Myeloma Patients Treated with Lenalidomide.
Mei-Hsi Chen, Connie Qi, Hong Chang. University Health Network, Toronto, Canada
Background: Lenalidomide is an oral immunomodulatory drug that has shown to improve overall survival in patients with relapsed or refractory multiple myeloma (MM). We recently reported that del(17p)(p53) is a poor prognostic factor in relapsed/refractory MM patients treated with lenalidomide. However, it is unclear whether aberrant p53 expression detected by immunohistochemistry (IHC) can be used as a surrogate to predict del(17p(p53) and adverse outcome in lenalidmode treated MM patients.
Design: The p53 expression was evaluated by IHC in decalcified, paraffin-embedded bone marrow biopsies from 88 refractory or relapsed MM patients prior to lenalidomide therapy. Clonal plasma cells of the bone marrow aspirates from the same cohort were examined for 17p (p53) gene status by interphase cytoplasmic interphase fluorescence in situ hybridization (FISH).
Results: Of 88 patients, FISH detected a hemizygous 17p(p53) deletion in 13 (13.6%) while IHC detected aberrant p53 nuclear expression in 11 (12.5%) of the cases. Of the 13 del(17p) positive cases, 11 (84.6%) expressed p53 detected by IHC, whereas all (100%) of the 11 IHC p53 positive cases had del(17p) (p53) by FISH. del(17p) (p53) and p53 expression were strongly correlated (P <0.001). Furthermore, patients with p53 expression had a significantly shorter progression free survival (median 6.1 vs 19.0 months, P=0.042), and a trend toward a shorter overall survival (7.2 vs 28.2 months, p= 0.058) than those without p53 expression.
Conclusions: Our results indicate that hemizygous p53 deletion is associated with aberrant p53 protein expression detected by IHC. p53 IHC my be used as a simple, rapid method to predict p53 deletion as a poor prognostic marker for risk stratification of MM receiving lenalidomide therapy.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 249, Tuesday Morning