p53 expression by immunohistochemistry is an important determinant of survival in patients with chronic lymphocytic leukemia receiving frontline chemo-immunotherapy.
Although chromosome 17p abnormalities and TP53 mutations have been reported as poor prognostic indicators in chronic lymphocytic leukemia (CLL), the impact of aberrant p53 expression as assessed by immunohistochemistry (p53-IHC) has not been defined in patients with CLL treated with chemoimmunotherapy, particularly in the context of other novel markers such as ZAP-70 expression and IgVH mutation status (IgVH MS). We assessed p53-IHC in 222 bone marrow (BM) specimens from patients with CLL enrolled in a phase II trial with fludarabine, cyclophosphamide, and rituximab (FCR). ZAP70 expression and IgVH MS were assessed in 208 and 108 patients, respectively. One hundred sixty-eight patients had concurrent classical cytogenetic analysis. p53-IHC correlated with abnormal karyotype (p = 0.002) and adversely affected overall survival independent of ZAP70 expression and IgVH MS (p < 0.001). Patients with p53-IHC(+) CLL were less likely to achieve complete remission, but patients who did achieve complete remission showed a durable response. In this patient cohort, p53-IHC is an important determinant of complete remission and overall survival, but not remission duration, in patients with CLL receiving FCR.
Schlette
Ellen J
EJ
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. eschlett@mdanderson.org
Admirand
Joan
J
Wierda
William
W
Abruzzo
Lynne
L
Lin
Katherine I
KI
O'Brien
Susan
S
Lerner
Susan
S
Keating
Michael J
MJ
Tam
Constantine
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001856:Bone Marrow Examination / Q000379:methods*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D015973:Gene Expression Regulation, Leukemic; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000069283:Rituximab; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000096:biosynthesis; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000032:analysis
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D000069283:Rituximab; D003520:Cyclophosphamide; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D014740:Vidarabine; C024352:fludarabine