The melanoma antigen gene as a surveillance marker for the detection of circulating tumor cells in patients with breast carcinoma

Kwon, Soim; Kang, Seok Hyung; Ro, Jungsil; Jeon, Chang‐Ho; Park, Jong‐Wook; Lee, Eun Sook

doi:10.1002/cncr.21162

Cited by 25 publications

(20 citation statements)

References 69 publications

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“…Among the MAGE families, the cluster MAGE-A, which has 12 subtypes (MAGE-A1-A12), has been observed most frequently in malignant tumors and has been characterized the best (5,8,11). Individual MAGE-A subtypes are expressed too sporadically and too weakly to be suitable for the detection of occult tumor cells (6); however, most carcinomas express at least one MAGE-A subtype (5,6).…”

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confidence: 99%

“…Individual MAGE-A subtypes are expressed too sporadically and too weakly to be suitable for the detection of occult tumor cells (6); however, most carcinomas express at least one MAGE-A subtype (5,6). Therefore, recent studies for the detection of occult tumor cells used either PCR primers that can simultaneously detect multiple MAGE-A subtypes in one reaction (5,17) or multimarker RT-PCR settings with different MAGE-A primer pairs (6,18). Using these MAGE-A RT-PCR assays, DTCs in bone marrow have been detected in 11 of 33 (33%) examined lung cancer patients without overt metastases (cM 0 ; ref.…”

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confidence: 99%

“…6), in 22 of 136 (16%) examined breast cancer patients without overt metastases (cM 0 ; ref. 5), and in 18 of 30 (60%) of prostate cancer patients without distant metastases (cM 0 ; ref. 6).…”

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Detection of MAGE-A Transcripts in Bone Marrow Is an Independent Prognostic Factor in Operable Non–Small-Cell Lung Cancer

Sienel

Mecklenburg

Dango

et al. 2007

Clinical Cancer Research

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Purpose: MAGE-A gene expression in humans is mostly restricted to tumor cells, and the role of MAGE-A transcripts and peptides as diagnostic markers and therapeutic targets is currently under investigation. Thus far, the clinical relevance of MAGE-A transcripts as marker for disseminated tumor cells in bone marrow of patients with operable lung cancer without overt metastases is still unclear. Experimental Design: Preoperative bone marrow aspirates from 50 consecutive patients with operable non^small-cell lung cancer free of distant metastases (i.e., pT 1-4 pN 0-2 M 0 R 0 ) were admitted to the study. Each bone marrow sample was divided and examined using multimarker MAGE-A reverse transcription-PCR (RT-PCR) and immunocytochemical staining with the antipancytokeratin antibody A45-B/B3. Multimarker MAGE-A RT-PCR consisted of multiple subtype-specific nested RT-PCRs with primers for MAGE-A1, MAGE-A2, MAGE-A3/6, MAGE-A4, and MAGE-A12. The median follow-up duration was 92 months (range, 18-110 months). Results:Twenty-six (52%) lung cancer patients harbored MAGE-A transcripts in their bone marrow, as opposed to none of the 30 healthy controls tested. In all 7 patients with immunocytochemically positive bone marrow, MAGE-A transcripts were also detected. All different MAGE-A subtypes (MAGE-A1, MAGE-A2, MAGE-A3/6, MAGE-A4, and MAGE-A12) were observed. Sixty-five percent of patients with MAGE-A transcripts in bone marrow exhibited only one subtype. Univariate (P = 0.03, log-rank-test) and multivariate survival analysis showed that MAGE-A transcripts in bone marrow were associated with poor outcome in pN 0 patients (P = 0.02; relative risk, 7.6). Conclusions: Detection of MAGE-A transcripts in bone marrow predicts an unfavorable outcome in patients with early-stage operable lung cancer. This finding indicates that MAGE-A transcripts are clinically relevant markers of micrometastatic spread in lung cancer and supports further investigation of MAGE-A as potential future therapeutic target.

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Detection of MAGE-A Transcripts in Bone Marrow Is an Independent Prognostic Factor in Operable Non–Small-Cell Lung Cancer

Sienel

Mecklenburg

Dango

et al. 2007

Clinical Cancer Research

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“…The present knowledge about NY-BR-1 expression is primarily based on RT-PCR analysis. However, knowledge about the actual protein expression of NY-BR-1 is crucial in assessing its therapeutic and diagnostic potential (2,4,10,11). We recently generated several mAbs to NY-BR-1 for the analysis of NY-BR-1 on a protein level.…”

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Preferential Nuclear and Cytoplasmic NY-BR-1 Protein Expression in Primary Breast Cancer and Lymph Node Metastases

Varga

Theurillat

Filonenko

et al. 2006

Clinical Cancer Research

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Purpose: NY-BR-1 is a recently isolated differentiation antigen, which is expressed in normal mammary tissue and in breast cancer. However, current data are based on RT-PCR analysis and nothing is known about the presence of NY-BR-1 on a protein level. We previously generated a monoclonal antibody to NY-BR-1to study the protein expression of NY-BR-1. Methods: In our immunohistochemical study, NY-BR-1was analyzed in normal tissues, various tumor types, 124 primary breast cancers, and 37 paired lymph node metastases. Results: Among normal tissues, NY-BR-1was present solely in ductal epithelium of the breast. In tumors, carcinoma in situ and invasive carcinoma of the breast were NY-BR-1 positive whereas other tumors and normal tissues were negative. Sixty percent of invasive breast carcinomas were NY-BR-1positive, displaying cytoplasmic and/or nuclear immunoreactivity.This coexpression was verified by confocal microscopy. Although the monoclonal antibody identified intratumoral heterogeneity, a majority (72%) of NY-BR-1-positive carcinomas revealed immunoreactivity in >50% of the tumor cells. NY-BR-1 expression was more frequent in estrogen receptor^positive and lymph node^negative primary carcinomas (P < 0.05 each) and was more common in grade 1 (77%) than in grade 2 (63%) or grade 3 (50%) carcinomas (P < 0.05). This suggests that NY-BR-1expression is lost with tumor progression. Forty-nine percent of lymph node metastases were NY-BR-1positive. Conclusion:This study supports the notion that NY-BR-1is a differentiation antigen of the breast, which is present in normal and tumorous mammary epithelium. The organ-specific expression of NY-BR-1and its high prevalence in metastases indicate that it could be a valuable target for cancer immunotherapy.

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“…There are several reports regarding to establishment of molecular diagnostic techniques for the early diagnosis of primary tumors, and also detection of rare occult tumor cells or DTC's using multiple molecular markers with definitive accuracy to malignancies including the one based on MAGE-A expression pattern [15,[23][24][25][26][27][28]. Therefore, in order to increase the sensitivity of the previously established methods, it was aimed to investigate the expression rate of mRNA transcripts of 10 different MAGE-A subtypes using RT-PCR in a large number of OSCC samples to determine whether multiple expression analysis of MAGE-A is a more sensitive application for the detection of OSCC.…”

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confidence: 99%

A novel Multiple-Marker Method for the Early Diagnosis of Oral Squamous Cell Carcinoma

et al. 2009

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Abstract. Objective: Melanoma associated antigens-A (MAGE-A) expression is highly specific to cancer cells. Thus, they can be the most suitable targets for the diagnosis of malignancy. The aim of this study was to evaluate the sensitivity of multiple MAGE-A expression analysis for the diagnosis of oral squamous cell carcinoma (OSCC). Methods: Total of 70 OSSC and 20 normal oral mucosal (NOM) samples of otherwise healthy volunteers were examined for the expression of 10 different single antigens out of 12 different MAGE-A subtypes by highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR) methods. The results were correlated to clinicopathological parameters of tumor samples. Results: Expression of MAGE-A was restricted to OSCC. The expression frequency of single antigen was between 10% and 55%. However, expression rate was increased up to 93% by the elevated number of genes examined. A significant correlation was found between the expression of MAGE-A and malignancy (p = 0.0001). In addition, multiple MAGE-A detection has also correlated to the incidence of lymph node metastasis, grading and advanced clinical stages. Conclusions: Analysis of multiple MAGE-A expression is more sensitive than the analysis of a single MAGE-A for the diagnostic evaluation of OSCC. Multiple MAGE-A expression analysis may be a very sensitive method to be used for the diagnosis even in the early stage of OSCC.

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The melanoma antigen gene as a surveillance marker for the detection of circulating tumor cells in patients with breast carcinoma

Cited by 25 publications

References 69 publications

Detection of MAGE-A Transcripts in Bone Marrow Is an Independent Prognostic Factor in Operable Non–Small-Cell Lung Cancer

Detection of MAGE-A Transcripts in Bone Marrow Is an Independent Prognostic Factor in Operable Non–Small-Cell Lung Cancer

Preferential Nuclear and Cytoplasmic NY-BR-1 Protein Expression in Primary Breast Cancer and Lymph Node Metastases

A novel Multiple-Marker Method for the Early Diagnosis of Oral Squamous Cell Carcinoma

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