Mammaglobin Gene Expression: A Superior Marker of Breast Cancer Cells in Peripheral Blood in Comparison to Epidermal-Growth-Factor Receptor and Cytokeratin-19

Grünewald, Kurt; Haun, Margot; Urbanek, M; Fiegl, Michael; Müller‐Holzner, Elisabeth; Gunsilius, Eberhard; Dünser, Martina; Marth, Christian; Gastl, Günther

doi:10.1038/labinvest.3780112

Cited by 103 publications

(64 citation statements)

References 15 publications

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“…Keratin 19 has been reported to be a useful marker for disseminated tumor cells in the blood in numerous studies (e.g., ref. 16), although others have reported elevated keratin 19 in similar percentages of healthy individuals and cancer patients (17). Both keratins in our study were found at elevated levels in the blood of most healthy individuals and cancer patients and hence were not useful markers.…”

Section: High-sensitivity Array Screening Of Candidate Markers In Bloodcontrasting

confidence: 43%

High-sensitivity array analysis of gene expression for the early detection of disseminated breast tumor cells in peripheral blood

Martin

Graner

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

118

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Early detection is an effective means of reducing cancer mortality. Here, we describe a highly sensitive high-throughput screen that can identify panels of markers for the early detection of solid tumor cells disseminated in peripheral blood. The method is a two-step combination of differential display and high-sensitivity cDNA arrays. In a primary screen, differential display identified 170 candidate marker genes differentially expressed between breast tumor cells and normal breast epithelial cells. In a secondary screen, high-sensitivity arrays assessed expression levels of these genes in 48 blood samples, 22 from healthy volunteers and 26 from breast cancer patients. Cluster analysis identified a group of 12 genes that were elevated in the blood of cancer patients. Permutation analysis of individual genes defined five core genes (P < 0.05, PERMAX test). As a group, the 12 genes generally distinguished accurately between healthy volunteers and patients with breast cancer. Mean expression levels of the 12 genes were elevated in 77% (10 of 13) untreated invasive cancer patients, whereas cluster analysis correctly classified volunteers and patients (P ‫؍‬ 0.0022, Fisher's exact test). Quantitative real-time PCR confirmed array results and indicated that the sensitivity of the assay (1:2 ؋ 10 8 transcripts) was sufficient to detect disseminated solid tumor cells in blood. Expression-based blood assays developed with the screening approach described here have the potential to detect and classify solid tumor cells originating from virtually any primary site in the body.breast cancer ͉ hematogeneous dissemination of tumor cells ͉ cDNA ͉ prognostic markers ͉ differential display

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Section: High-sensitivity Array Screening Of Candidate Markers In Bloodcontrasting

confidence: 43%

High-sensitivity array analysis of gene expression for the early detection of disseminated breast tumor cells in peripheral blood

Martin

Graner

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

118

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“…The hMAM gene was described to be a potentially specific marker for the detection of circulating breast cancer cells [34]. However, the clinical relevance of the detection of hMAM positivetumour cells in the peripheral blood of patients with localised breast cancer still remains elusive, since several papers report conflicting results [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Detection of human mammaglobin mRNA in serial peripheral blood samples from patients with non-metastatic breast cancer is not predictive of disease recurrence

Marques

Teixeira

Diamond

et al. 2008

Breast Cancer Res Treat

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International audienceHuman mammaglobin (hMAM) mRNA is a sensitive and specific marker of breast cancer cells. We evaluated if hMAM mRNA detection in serial peripheral blood samples from non-metastatic breast cancer patients predicts for disease recurrence. Patients scheduled for adjuvant or neoadjuvant chemotherapy were eligible. Serial blood samples were collected up to 5 years, the first before (neo)adjuvant chemotherapy. hMAM gene expression was analysed by RT-PCR. Specificity was evaluated in blood samples from healthy volunteers. A total of 321 patients were included. The incidence of pre-chemotherapy hMAM-positive samples was similar in patients who latter experienced cancer recurrence (22.4%) and those who remained disease-free (17.9%; = 0.46). Similarly, the mean number of positive follow-up samples was similar in both groups (0.15 ± 0.22 and 0.13 ± 013; = 0.29). Furthermore, there was no difference in disease-free (= 0.63) or overall survival (= 0.57) in patients with and without positive baseline samples or between patients whose follow-up samples were always hMAM negative and those with at least one positive sample. Multivariate survival analysis confirmed that hMAM mRNA detection before or after (neo)adjuvant chemotherapy was not predictive of recurrence. There is no evidence that hMAM mRNA detection at diagnosis or during follow-up predicts for breast cancer recurrence

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“…Previous studies have shown that mammaglobin mRNA levels were detectable at higher levels in breast tumors compared with normal breast tissue, and mammaglobin was not expressed at the RNA level in several normal tissues (3). Moreover, mammaglobin protein expression in breast tumors was observed at high frequency (3,15,16) independent of stage, grade, or histology (2). This evidence of breast tissue specificity has led to the application of mammaglobin as a marker for metastatic spread of breast cancer to lymph nodes (5).…”

Section: Discussionmentioning

confidence: 99%

Identification of Mammaglobin as a Novel Serum Marker for Breast Cancer

Bernstein

Godbold

Raptis

et al. 2005

Clinical Cancer Research

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Purpose: Early detection of breast cancer has implications for the management and treatment of patients with this disease. Currently, there exist no highly sensitive and specific serologic biomarkers for detection of breast cancer. Mammaglobin is predicted to be a secreted protein, and expression of this gene seems to be highly specific in breast cancer. The present studies were undertaken to develop the mammaglobin protein as a serum biomarker for detection of breast cancer. Experimental Design: We characterized the mammaglobin protein as a secreted, 14-to 21-kDa species, which is likely post-translationally processed based on its predicted 7-kDa size. Immunostaining for mammaglobin was conducted. An ELISA was developed for the detection of the mammaglobin protein in serum, and levels were compared between women with and without breast cancer. A receiver operating characteristic curve was used to show sensitivity and specificity for cut points on the continuous mammaglobin scale. Results:The protein was detectable by immunostaining in 72% of breast tumors and not in other tumor types.The ELISA was highly sensitive and specific for detection of mammaglobin protein in tissue culture fluids of breast cancer cells and sera of breast cancer patients. The ELISA differentiated healthy women from those with breast cancer with accurate, repeatable results across time and under varying storage conditions. Conclusion: Our results indicate that mammaglobin, as measured by the ELISA, holds significant promise for breast cancer screening with the realistic potential to impact management of this disease.

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Mammaglobin Gene Expression: A Superior Marker of Breast Cancer Cells in Peripheral Blood in Comparison to Epidermal-Growth-Factor Receptor and Cytokeratin-19

Cited by 103 publications

References 15 publications

High-sensitivity array analysis of gene expression for the early detection of disseminated breast tumor cells in peripheral blood

High-sensitivity array analysis of gene expression for the early detection of disseminated breast tumor cells in peripheral blood

Detection of human mammaglobin mRNA in serial peripheral blood samples from patients with non-metastatic breast cancer is not predictive of disease recurrence

Identification of Mammaglobin as a Novel Serum Marker for Breast Cancer

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