Ki67 and PIM1 expression predict outcome in mantle cell lymphoma treated with high dose therapy, stem cell transplantation and rituximab: a Cancer and Leukemia Group B 59909 correlative science study.
The proliferation index in mantle cell lymphoma (MCL) has not been validated in the context of aggressive therapy regimens in the rituximab era. We assessed Ki67 and PIM1 (a cell cycle-related gene upregulated in blastoid MCL) expression by immunohistochemistry in a phase II study Cancer and Leukemia Group B 59909 of aggressive chemotherapy and rituximab followed by autologous stem cell transplantation plus rituximab in untreated MCL patients <70 years of age. As a continuous variable or using a cutoff of 35%, higher image analysis (IA Ki67, n = 52) was associated with shorter progression free survival (PFS) (P < or = 0.030) and event free survival (EFS) (P < or = 0.017). PIM1 expression (n = 50) was associated with PFS (P = 0.033) and EFS (P = 0.043). Bivariate Cox models showed IA Ki67 and PIM1 were independent of clinical factors. High Ki67 (>35%) is an important independent prognostic marker in aggressively treated MCL in the rituximab era. PIM1 expression predicts poor outcome and, given its potential role as a therapeutic target, deserves further study.
Hsi
Eric D
ED
Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH 44195, USA. hsie@ccf.org
Jung
Sin-Ho
SH
Lai
Raymond
R
Johnson
Jeffrey L
JL
Cook
James R
JR
Jones
Dan
D
Devos
Sven
S
Cheson
Bruce D
BD
Damon
Lloyd E
LE
Said
Jonathan
J
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis*; D020522:Lymphoma, Mantle-Cell / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D051573:Proto-Oncogene Proteins c-pim-1 / Q000032:analysis*; D000069283:Rituximab; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D000069283:Rituximab; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1