A critical evaluation of loss of heterozygosity detected in tumor tissues, blood serum and bone marrow plasma from patients with breast cancerReport as inadecuate




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Breast Cancer Research

, 9:R66

First Online: 03 October 2007Received: 28 June 2007Revised: 03 September 2007Accepted: 03 October 2007

Abstract

IntroductionThe aim of the study was to perform a comparative analysis of LOH loss of heterozygosity in primary tumors as well as peripheral blood and bone marrow BM of patients with breast cancer BCa.

MethodsPerforming PCR-based fluorescence microsatellite analysis and using a panel of seven polymorphic microsatellite markers, we compared the profiles of LOH in primary tumors, peripheral blood and BM plasma from patients with primary BCa n = 40, stage M0 as well as tumor tissues and blood serum from metastatic BCa patients n = 48, stage M1. During the course of systemic treatment blood samplings from 12 M0 and 16 M1 patients were at least once repeated.

ResultsThe overall incidences of LOH in tumor tissues, blood and BM samples were 27.5%, 9.0% and 5.0%, respectively. The marker D3S1255 was the only one in the panel that showed similar frequencies of LOH ranging from 19.0 to 24.5% in tumor, blood and BM samples. Both M0 blood serum and BM plasma samples displayed the same rate of 19.0%, whereas tumor and M1 serum showed a rate of 24.5% and 24.0%, respectively, at this locus. This marker also showed the highest frequency of LOH in serum and BM samples, whereas in tumor samples LOHs at the markers D13S218 38% and D17S855 36% were more frequent. Statistical analysis of the tumor samples showed that occurrence of LOH at the markers D3S1255 P < 0.04, D9S171 P < 0.05 and D17S855 P < 0.03 correlated with undifferentiated nuclear grade. Additionally, significant associations of the number of LOH recorded at D17S250 with estrogen receptor P < 0.02, progesterone receptor P < 0.03 expression and high proliferation score Ki-67 expression, P = 0.009 were observed. In blood serum samples a relationship between positive lymph node status and LOH at the marker D3S1255 was revealed M0 stage, P = 0.05; M0+M1 stage, P = 0.004.

ConclusionOur study demonstrates heterogeneous profiles and low rates of LOH, particularly on free DNA in BM and blood samples. However, the significant associations of LOH with some risk factors and the demonstrated possibility of monitoring free DNA in patients undergoing systemic therapy suggest that LOH analysis may be developed into a useful diagnostic tool.

AbbreviationsBCabreast cancer

BMbone marrow

LOHloss of heterozygosity.

Electronic supplementary materialThe online version of this article doi:10.1186-bcr1772 contains supplementary material, which is available to authorized users.

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Author: Heidi Schwarzenbach - Volkmar Müller - Cord Beeger - Miriam Gottberg - Nicole Stahmann - Klaus Pantel

Source: https://link.springer.com/







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