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Mammaglobin Remains a Useful Marker for the Detection of Breast Cancer Cells in Peripheral Blood

Elisabethinen Hospital, 1st Department of Internal Medicine, Linz, Austria

To the Editor:

Recently, Span et al¹ reported results concerning quantification of mammaglobin expression in tumor tissues from breast cancer patients, finding an association of high expression with low-grade, steroid receptor–positive tumors from postmenopausal patients. However, tumors from 19 of 280 patients (6.8%) were mammaglobin negative after 40 rounds of amplification by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Due to the differences of mammaglobin expression in tumor tissues from various breast cancer patients it was argued that mammaglobin is not a useful marker for the detection of circulating tumor cells.

In 1999, we published a nested RT-PCR assay for the detection of tumor cells in peripheral blood of breast cancer patients using mammaglobin as a marker.² In addition, we established a quantitative RT-PCR assay and measured the amount of mammaglobin mRNA molecules in tumor tissues from 52 breast cancer patients (unpublished data). According to Span et al, we found a wide range in the amount of mammaglobin expression after normalization for ß-actin expression, but 2 of 52 tumor samples (3.8%) were mammaglobin negative in quantitative RT-PCR. However, by applying the nested RT-PCR assay, we were able to detect mammaglobin mRNA molecules in both negative samples, too. The nested RT-PCR assay is capable of detecting mammaglobin mRNA molecules even in samples with very low expression levels³; hence, negative results using other detection methods might be caused by lower sensitivity compared with nested RT-PCR.

The correlation of high mammaglobin expression in tumor tissues with favorable clinicopathologic features described by Span et al does not imply that this molecule is unsuitable as a marker for circulating tumor cells. A good tumor-cell marker should exhibit high specificity for a certain cell or tumortype; this criterion is fulfilled by mammaglobin for cells derived from breast tissue. Certainly, circulating tumor cells can exhibit different gene-expression profiles compared with the primary tumor—single tumor cells might have lost the ability to express mammaglobin mRNA—but this can also be true for other marker genes. The crucial point is that all 52 tumor samples from breast cancer patients tested so far were mammaglobin positive when using nested RT-PCR. Considering the absence of mammaglobin expression in blood cells, we conclude that this molecule still remains a suitable marker for the detection of circulating tumor cells, independent of its expression amount in individual breast cancer cells.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Span PN, Waanders E, Manders P, et al: Mammaglobin is associated with low-grade, steroid receptor-positive breast tumors from postmenopausal patients, and has independent prognostic value for relapse-free survival. J Clin Oncol 22:691-698, 2004[Abstract/Free Full Text]

2. Zach O, Kasparu H, Krieger O, et al: Detection of circulating mammary carcinoma cells in the peripheral blood of breast cancer patients via a nested reverse transcriptase polymerase chain reaction assay for mammaglobin mRNA. J Clin Oncol 17:2015-2019, 1999[Abstract/Free Full Text]

3. Zach O, Wagner H, Kasparu H, et al: Statistical validation of the mammaglobin-nested RT-PCR assay for tumor cell detection in blood of breast cancer patients. BioTechniques 31:1358-1362, 2001[Medline]

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• In Reply:
  P.N. Span, C.G.J. Sweep, L.V.A.M. Beex, and J.A. Foekens
  JCO 2005 23: 3160-3161 [Full Text]

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zach, O. Articles by Lutz, D. Search for Related Content PubMed PubMed Citation Articles by Zach, O. Articles by Lutz, D. Related Articles Related Reply Social Bookmarking                            What's this?