Fluorescence in situ hybridization detection of cytogenetic abnormalities and prognosis in multiple myeloma

We evaluated the prognosis of patients with newly diagnosed multiple myeloma (MM) and attempted to find a suitable treatment strategy for them. Interphase fluorescence in situ hybridization (FISH) detection was performed on 57 patients with MM. The following probes: IgH, p53, 1q21, RB1, and D13S319 specific for the rearrangements of 14q32, 17p13, 1q21 and 13q14 were used. Fluorescent hybridization signals were observed using an Olympus BX60 epifluorescence microscope equipped with filters for detecting fluoroisothiocyanate (FITC), Texas red, and 4'-6-Diamidino-2-phenylindole (DAPI). Triple color clone-specific images were captured using a Quips XL genetic workstation. The mortalities in patients with moderate prognosis (66.7%) and poor prognosis (50%) were significantly higher compared with that in patients with good prognosis (15%, P<0.05). All the patients in good and moderate prognosis groups achieved complete remission (CR)/very good partial remission (VGPR)/partial remission (PR), whereas only half of the cases in the poor prognosis group reached this level. Patients 2 supported by autologous hematopoietic stem-cell transplantation presented CR/PR and long survival. For those with poor prognosis, a proper therapeutic regimen and timely transplantation, especially tandem transplantation, was necessary due to the rapid progression and complications.

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Interphase fluorescence in situ hybridization in multiple myeloma and monoclonal gammopathy of undetermined significance without and with positive plasma cell identification: analysis of 192 cases from the Region of Southern Denmark

Cancer Genetics and Cytogenetics ◽

10.1016/j.cancergencyto.2006.11.015 ◽

2007 ◽

Vol 174 (2) ◽

pp. 89-99 ◽

Cited By ~ 20

Author(s):

Jacob H. Christensen ◽

Niels Abildgaard ◽

Torben Plesner ◽

Anne Nibe ◽

Ole Nielsen ◽

...

Keyword(s):

Multiple Myeloma ◽

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Plasma Cell ◽

Monoclonal Gammopathy ◽

Cell Identification ◽

Identification Analysis ◽

Undetermined Significance

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Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2

Blood ◽

10.1182/blood-2010-10-300970 ◽

2011 ◽

Vol 117 (18) ◽

pp. 4696-4700 ◽

Cited By ~ 221

Author(s):

Nikhil C. Munshi ◽

Kenneth C. Anderson ◽

P. Leif Bergsagel ◽

John Shaughnessy ◽

Antonio Palumbo ◽

...

Keyword(s):

Multiple Myeloma ◽

In Situ Hybridization ◽

High Risk ◽

Risk Stratification ◽

Fluorescence In Situ Hybridization ◽

High Serum ◽

Β2 Microglobulin ◽

Poor Outcome ◽

13Q Deletion

Abstract A panel of members of the 2009 International Myeloma Workshop developed guidelines for risk stratification in multiple myeloma. The purpose of risk stratification is not to decide time of therapy but to prognosticate. There is general consensus that risk stratification is applicable to newly diagnosed patients; however, some genetic abnormalities characteristic of poor outcome at diagnosis may suggest poor outcome if only detected at the time of relapse. Thus, in good-risk patients, it is necessary to evaluate for high-risk features at relapse. Although detection of any cytogenetic abnormality is considered to suggest higher-risk disease, the specific abnormalities considered as poor risk are cytogenetically detected chromosomal 13 or 13q deletion, t(4;14) and del17p, and detection by fluorescence in situ hybridization of t(4;14), t(14;16), and del17p. Detection of 13q deletion by fluorescence in situ hybridization only, in absence of other abnormalities, is not considered a high-risk feature. High serum β2-microglobulin level and International Staging System stages II and III, incorporating high β2-microglobulin and low albumin, are considered to predict higher risk disease. There was a consensus that the high-risk features will change in the future, with introduction of other new agents or possibly new combinations.

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Frequent gain of chromosome band 1q21 in plasma-cell dyscrasias detected by fluorescence in situ hybridization: incidence increases from MGUS to relapsed myeloma and is related to prognosis and disease progression following tandem stem-cell transplantation

Blood ◽

10.1182/blood-2006-03-009910 ◽

2006 ◽

Vol 108 (5) ◽

pp. 1724-1732 ◽

Cited By ~ 267

Author(s):

Ichiro Hanamura ◽

James P. Stewart ◽

Yongsheng Huang ◽

Fenghuang Zhan ◽

Madhumita Santra ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Disease Progression ◽

Monoclonal Gammopathy ◽

Poor Prognosis ◽

Chromosome Band ◽

Newly Diagnosed ◽

Poor Prognostic Factor ◽

Plasma Cell Dyscrasias

Using fluorescence in situ hybridization we investigated amplification of chromosome band 1q21 (Amp1q21) in more than 500 untreated patients with monoclonal gammopathy of undetermined significance (MGUS; n = 14), smoldering multiple myeloma (SMM; n = 31), and newly diagnosed MM (n = 479) as well as 45 with relapsed MM. The frequency of Amp1q21 was 0% in MGUS, 45% in SMM, 43% in newly diagnosed MM, and 72% in relapsed MM (newly diagnosed versus relapsed MM, P < .001). Amp1q21 was detected in 10 of 12 patients whose disease evolved to active MM compared with 4 of 19 who remained with SMM (P < .001). Patients with newly diagnosed MM with Amp1q21 had inferior 5-year event-free/overall survival compared with those lacking Amp1q21 (38%/52% versus 62%/78%, both P < .001). Thalidomide improved 5-year EFS in patients lacking Amp1q21 but not in those with Amp1q21 (P = .004). Multivariate analysis including other major predictors revealed that Amp1q21 was an independent poor prognostic factor. Relapsed patients who had Amp1q21 at relapse had inferior 5-year postrelapse survival compared with those lacking Amp1q21 at relapse (15% versus 53%, P = .027). The proportion of cells with Amp1q21 and the copy number of 1q21 tended to increase at relapse compared with diagnosis. Our data suggest that Amp1q21 is associated with both disease progression and poor prognosis.

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HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.8.2894 ◽

1997 ◽

Vol 15 (8) ◽

pp. 2894-2904 ◽

Cited By ~ 539

Author(s):

M F Press ◽

L Bernstein ◽

P A Thomas ◽

L F Meisner ◽

J Y Zhou ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Gene Amplification ◽

Poor Prognosis ◽

Southern Hybridization ◽

Recurrent Disease ◽

Breast Cancers ◽

Node Negative ◽

Her 2

PURPOSE The HER-2/neu gene codes for a membrane receptor protein that is homologous, but distinct from the epidermal growth factor receptor. This investigation was performed to validate fluorescence in situ hybridization (FISH) as a sensitive and specific method for assessing HER-2/neu gene amplification in archival tissue and to test whether this alteration is associated with poor prognosis. MATERIALS AND METHODS HER-2/neu gene amplification was determined by FISH in 140 archival breast cancers, previously characterized for gene amplification by Southern hybridization or dot-blot hybridization, and for gene expression by Northern hybridization, Western immunoblot, or immunohistochemistry. A separate cohort of 324 node-negative breast cancers was assessed for amplification by FISH to determine the utility of HER-2/neu gene amplification. RESULTS Relative to solid-matrix blotting procedures, FISH analysis of HER-2/neu gene amplification showed a sensitivity of 98% and a specificity of 100% in 140 breast cancers. Among patients treated by surgery only, the relative risks (relative hazard) of early recurrence (recurrent disease within 24 months of diagnosis), recurrent disease (at any time), and disease-related death were statistically significantly associated with amplification. The prognostic information contributed by HER-2/neu amplification was independent of the other markers studied. CONCLUSION FISH was an alternative technique for determining gene amplification and had some distinct advantages over Southern hybridization. Our results demonstrate that HER-2/neu gene amplification in the absence of adjuvant therapy is an independent predictor of poor clinical outcome and is a stronger discriminant than tumor size. Women with small tumors that had gene amplification were at increased risk of recurrence and disease-related death.

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