Elevated mammaglobin (h-MAM) expression in breast cancer is associated with clinical and biological features defining a less aggressive tumour phenotype.

Mj Núñez-Villar,Ar Lucas,A Tejerina,J Schneider,M Pollán,J Sánchez,F Martínez-Arribas

doi:10.1186/bcr587

Abstract

Mammaglobin (h-MAM) is expressed mainly by breast epithelial cells, and this feature has been used to detect circulating breast cancer cells and occult metastases in sentinel axillary lymph nodes of breast cancer patients. However, the biological role of mammaglobin is completely unknown. We studied 128 fresh-frozen breast cancer specimens by means of reverse transcriptase-polymerase chain reaction and quantified their h-MAM mRNA expression. This was then correlated with histological and nuclear grade, oestrogen and progesterone receptor expression, c-erb-B2 and mutant p53 expression, as well as with cellular proliferation measured by means of the Ki67 labelling index, DNA ploidy and S-phase, and finally with the presence or not of invaded axillary nodes in the mastectomy specimen. In the univariate analysis, high h-MAM expression (above the median for the whole group) correlated significantly (P < 0.05) with oestrogen and progesterone receptor expression, diploid DNA content, low Ki67 labelling index, low nuclear grade and almost significantly (P = 0.058) with the absence of axillary nodal invasion in the mastectomy specimen. In a final, multivariate model, only progesterone receptor expression, diploid DNA content and absence of nodal invasion were found to be independently associated with high h-MAM expression. All of the features associated with mammaglobin expression reflect, without exception, a less aggressive tumour phenotype. Further studies are needed to clarify whether this is attributable to h-MAM expression itself, or to another mechanism of which mammaglobin expression forms part.

Highlights

The human mammaglobin (h-MAM) gene was recently cloned by Watson and colleagues [1]
Mammaglobin expression has been observed in breast epithelial cells, but not in myoepithelial or stromal breast cells [3]
There was no difference in h-MAM expression between tumours from previously treated and untreated patients (Table 1), or between tumours belong- R67

Summary

Introduction

The human mammaglobin (h-MAM) gene was recently cloned by Watson and colleagues [1]. It maps to chromosome 11q12-13, and the amino acid sequence it encodes is similar to that of epithelial secretory proteins belonging to the uteroglobin family, all of which are encoded by genes clustered on the same chromosomal region [2]. Zach and colleagues [4] were not able to detect mammaglobin expression by means of reverse transcriptase–polymerase chain reaction (RT–PCR) in the human uterus, ovary or leukocytes [4]. The same authors had used mammaglobin experimentally to bp = base pairs; RT–PCR = reverse transcriptase–polymerase chain reaction.

Methods

Results

Discussion

Conclusion