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  • Open Access

Mammaglobin as a marker in breast cancer

  • 1
Breast Cancer Research20002:66689

https://doi.org/10.1186/bcr-2000-66689

  • Published:

Keywords

  • Mammaglobin
  • metastasis
  • RT-PCR

Introduction

Despite apparent curative resection, subsequent development of metastatic spread presents a major clinical problem in about 30% of all breast cancer patients. In recent years the RT-PCRtechnique has been used as a means of detecting circulating carcinoma cells in blood or bone marrow. Epithelial markers which have been used to date include cytokeratins, muc-1, epidermal growth factor receptor (EGF-R) or erbB2; however, these markers are not always specific for tumour cells. Recently, expression of the human mammaglobin (hMAM) gene has been suggested as a more specific marker for detecting circulating breast tumour cells in blood.The hMAM gene belongs to the uteroglobin gene family and is found on chromosome 11q12.3-13.1, a region frequently amplified in breast cancer.

Aims

To compare gene expression of hMAM with that of the more conventional markers, cytokeratin-19 (CK19) and EGF-R and to examine the relationship between expression of these markers and clinical outcome.

Comments

The development of suitable methods to detect blood-borne metastasis has been the goal of many laboratories recently. Although initial studies were promising, it was subsequently shown that many of the markers used were not entirely tumour-specific. Here, expression of mammaglobin, a mammary-gland-specific gene, was compared with other more conventionally used molecular markers. The high specificity of mammaglobin for breast cancer cells suggests that a specific marker of blood borne metastasis of breast cancer cells has finally been identified. This has potential use as a marker to detect early metastatic spread.

Methods

Blood samples were collected from patients with ductal carcinoma in situ(n = 12), invasive breast cancer (n = 133), haematological malignancies (n = 20) and healthy volunteers (n = 31). Primary human tumour material from 40 breast cancer patients was also analysed. Total RNA was extracted and reverse transcribed into cDNA. This was amplified by nested RT-PCR using primers designed to detect hMAM, EGF-R and CK-19 genes and analysed by gel electrophoresis. RNA from the cell line MDA-MB-361 served as a positive control.

Results

hMAM, EGF-R and CK-19 were detected in breast cancer tissue and the cell line MDA-MB-361. None of the blood samples from healthy volunteers or from patients with haematological malignancies was positive for hMAM. CK-19 was detected in blood from 39% of normal volunteers, while EGF-R and erbB2 were found in blood samples from patients with haematological malignancies (25% and 10%, respectively). In blood samples from patients with invasive breast cancer, mRNAs for hMAM, EGF-R and CK-19 were found in 8%, 10% and 48% respectively. Expression of EGF-R or CK19 in blood samples from breast cancer patients was not correlated with clinicopathological features; however, there was a correlation between expression of hMAM and node status, metastasis and levels of serum CA15-3.

Discussion

In comparison with other molecular markers, the presence of hMAM transcripts in blood of breast cancer patients represents a superior marker to detect breast cancer spread. hMAM correlates with established clinical prognostic indicators; however, prospective studies are required to establish its possible prognostic impact.

Authors’ Affiliations

(1)
Molecular Medicine Unit, University of Leeds, UK

References

  1. Grunewald K, Haun M, Urbanek M, Fiegl M, Muller-Holzner E, Gunsilius E, Dunser M, Marth C, Gastl G: Mammaglobin gene expression: a superior marker of breast cancer cells in peripheral blood in comparison to epidermal growth factor receptor or cytokeratin-19. Lab Invest. 2000, 80: 1071-1077.View ArticlePubMedGoogle Scholar

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