Summary
Hemizygous TP53 deletion is an adverse risk factor in multiple myeloma (MM) but its relationship with p53 protein expression is unclear. We investigated 105 newly diagnosed myeloma patients and correlated nuclear p53 protein immunoreactivity with TP53 deletion status, myeloma‐associated genetic risk factors and survival. Fluorescence in situ hybridisation (FISH) detected hemizygous TP53 deletions in 13 (12%) patients while immunohistochemistry detected nuclear p53 protein expression in 12 (11%). Ten (77%) of the 13 del(TP53) cases expressed nuclear p53 protein while 10 (83%) of the 12 nuclear p53 immunoreactive cases had hemizygous TP53 deletions. Hemizygous TP53 deletion and p53 protein expression were strongly correlated (P < 0·001). The overall survival of patients with p53 protein expression was significantly shorter than that of patients without p53 expression (P < 0·001). A multivariate analysis including other myeloma‐associated genetic risk factors confirmed p53 expression as an independent risk factor for survival. Our data indicate that nuclear p53 protein expression, detected by a widely available immunohistochemical method, is strongly associated with TP53 deletion and an adverse clinical outcome for MM.
SummaryThe combination of fluorescence in situ hybridization with cytoplasmic light chain detection identified chromosome 1p21 deletion in 18 (20%) of 87 patients with multiple myeloma. 1p21 deletion was associated with higher serum calcium level, 13q deletion, and t(4;14). Patients with 1p21 deletions had a significantly shorter progression-free survival (PFS) (median 10AE5 vs. 22AE3 months, P ¼ 0AE0002) and shorter overall survival (OS) (median 33AE9 months vs. not reached, P ¼ 0AE002) than those without 1p21 deletions. On multivariate analysis, which included deletions of 13q, TP53, t(4;14) and CKS1B amplification, 1p21 deletion remained as an independent risk factor for PFS (P ¼ 0AE01) and OS (P ¼ 0AE04).
SummaryThe genetic events that lead to tumour progression in plasma cell dyscrasia are not well understood. Interphase cytoplasmic fluorescence in situ hybridisation was used to investigate the CKS1B amplification status (at 1q21) in clonal plasma cells from 123 patients: 23 monoclonal gammopathy of undetermined significance (MGUS), 75 multiple myeloma (MM) and 26 plasma cell leukaemia (PCL). While CKS1B amplification was absent in MGUS patients, such amplification (3-8 copies) was detected in 36% of newly diagnosed MM, 52% relapsed MM and 62% PCL (P < 0AE001). Our results suggest that CKS1B amplification is associated with transformation from MGUS to MM and progression to PCL.Keywords: plasma cell dyscrasia, CKS1B, fluorescence in situ hybridisation, tumour progression, monoclonal gammopathy of undetermined significance.short report ª
As patients with multiple myeloma (MM) have a variable clinical course, predictive markers would help determine the appropriate treatment strategy. Clinical staging is commonly used to predict outcome, but tumour marker expression and the underlying genetic changes are increasingly used to assess the biological aggressiveness of the disease. Recent studies have demonstrated the utility of immunohistochemistry in detecting prognostic markers, including fibroblast growth factor receptor 3, cyclin D1, c-maf and p53, which have been associated with various genetic aberrations, including t(4;14), t(11;14), t(14;16) and del(17p). While t(4;14), t(14;16) and del (17p) have been documented to confer a poor prognosis, t(11;14) appears to be a neutral or even favourable factor in some studies. CD56, CD33, CD20 and CXCR4 are promising surface markers due to their roles in MM progression, but further studies of larger cohorts are necessary to assess their prognostic relevance. In this review, the biological function and clinical relevance of the main prognostic markers in MM is discussed, and also the role of immunohistochemistry in the stratification of patients into appropriate risk categories.
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