Abstract
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.
MeSH terms
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Adult
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Aged
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Aged, 80 and over
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal, Murine-Derived
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Biomarkers, Tumor / analysis*
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Biomarkers, Tumor / genetics
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Bone Marrow Examination / methods*
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Combined Modality Therapy
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Cyclophosphamide / administration & dosage
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Female
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Follow-Up Studies
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Gene Expression Regulation, Leukemic*
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Genes, p53*
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Humans
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Immunohistochemistry*
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Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
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Leukemia, Lymphocytic, Chronic, B-Cell / genetics
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Leukemia, Lymphocytic, Chronic, B-Cell / mortality
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Leukemia, Lymphocytic, Chronic, B-Cell / pathology
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Male
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Middle Aged
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Prognosis
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Rituximab
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Somatic Hypermutation, Immunoglobulin / genetics
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Survival Analysis
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Tumor Suppressor Protein p53 / analysis*
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Tumor Suppressor Protein p53 / biosynthesis
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Vidarabine / administration & dosage
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Vidarabine / analogs & derivatives
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Young Adult
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ZAP-70 Protein-Tyrosine Kinase / analysis
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Murine-Derived
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Biomarkers, Tumor
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Tumor Suppressor Protein p53
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Rituximab
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Cyclophosphamide
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human
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Vidarabine
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fludarabine