Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Solitary Fibrous Tumors/diagnostic imaging , Solitary Fibrous Tumors/pathology , Adult , Biopsy, Large-Core Needle , Breast Neoplasms/surgery , Female , Humans , Mammography , Positron Emission Tomography Computed Tomography , Solitary Fibrous Tumors/surgeryABSTRACT
Myc (c-Myc) counteracts p27 effects, and low p27 usually correlates with high Myc expression in human cancer. However there is no information on the co-expression of both genes in chronic lymphocytic leukemia (CLL). We found a lack of correlation between RNA and protein levels of p27 and Myc in CLL cells, so we determined the protein levels by immunoblot in 107 cases of CLL. We observed a high p27 protein expression in CLL compared to normal B cells. Ectopic p27 expression in a CLL-derived cell line resulted in cell death resistance. Surprisingly, Myc expression was very low or undetectable in most CLL cases analyzed, with a clear correlation between high p27 and low Myc protein levels. This was associated with low Skp2 expression, which is consistent with the Skp2 role in p27 degradation and with SKP2 being a Myc target gene. High Myc expression did not correlate with leukemia progression, despite that cell cycle-related Myc target genes were upregulated. However, biochemical analysis showed that the high p27 levels inhibited cyclin-Cdk complexes even in Myc expressing CLL cells. Our data suggest that the combination of high p27 and low Myc is a marker of CLL cells which is mediated by Skp2.
Subject(s)
Cyclin-Dependent Kinase Inhibitor p27/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Proto-Oncogene Proteins c-myb/metabolism , S-Phase Kinase-Associated Proteins/metabolism , Adult , Aged , Aged, 80 and over , Apoptosis/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Cycle/genetics , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p27/genetics , Cyclins/genetics , Cyclins/metabolism , Drug Resistance, Neoplasm/genetics , Female , Gene Expression Regulation, Leukemic , Humans , Immunoblotting , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Microscopy, Fluorescence , Middle Aged , Proto-Oncogene Proteins c-myb/genetics , Reverse Transcriptase Polymerase Chain Reaction , S-Phase Kinase-Associated Proteins/geneticsABSTRACT
We evaluated the validity and accuracy of cytomorphology and multiparametric flow cytometry (C-FCM) in diagnosing oncohematologic disease in 223 consecutive lymph node biopsy specimens from patients with lymphadenopathy, from 2004 to 2007. C-FCM and histopathologic studies were interpreted independently by hematologists and pathologists, respectively. C-FCM detected neoplastic disorders in 133 samples (59.6%): 92 non-Hodgkin lymphomas (NHLs; 41.3%), 21 Hodgkin lymphomas (HLs; 9.4%), 19 malignant nonhematologic neoplasms (8.5%), and 1 multiple myeloma (0.4%). Sensitivity and specificity were 87.25% and 95.95%, respectively. Positive predictive value and negative predictive value (NPV) were 97.74% and 78.89%, respectively. Sensitivity and NPV were 94.79% and 96.81% upon excluding HL and malignant nonhematologic neoplasms from the analysis. Of the 92 NHLs, 89 (97%) were categorized according to the 2001 World Health Organization classification of hematolymphoid neoplasms with a concordance of 87%. The C-FCM study was significantly faster than the histopathologic study. C-FCM has high sensitivity and specificity, allowing for a valid and reliable diagnosis, especially in NHLs and enabling their subclassification. C-FCM is faster than the histopathologic examination, allowing for therapeutic decisions to be made quickly. However, in the samples in which C-FCM cannot establish a diagnosis, histopathologic results are needed.
