Núñez-Villar M J, Martínez-Arribas F, Pollán M, Lucas A R, Sánchez J, Tejerina A, Schneider J
Fundación Tejerina-Centro de Patología de la Mama, Madrid, Spain.
Breast Cancer Res. 2003;5(3):R65-70. doi: 10.1186/bcr587. Epub 2003 Mar 6.
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.
乳腺珠蛋白(h-MAM)主要由乳腺上皮细胞表达,这一特性已被用于检测乳腺癌患者循环中的癌细胞以及前哨腋窝淋巴结中的隐匿转移灶。然而,乳腺珠蛋白的生物学作用完全未知。
我们通过逆转录聚合酶链反应研究了128份新鲜冷冻的乳腺癌标本,并对其h-MAM mRNA表达进行定量。然后将其与组织学和核分级、雌激素和孕激素受体表达、c-erb-B2和突变型p53表达相关联,以及与通过Ki67标记指数、DNA倍体和S期测量的细胞增殖相关联,最后与乳房切除标本中是否存在腋窝淋巴结转移相关联。
在单变量分析中,高h-MAM表达(高于全组中位数)与雌激素和孕激素受体表达、二倍体DNA含量、低Ki67标记指数、低核分级显著相关(P < 0.05),并且与乳房切除标本中无腋窝淋巴结转移几乎显著相关(P = 0.058)。在最终的多变量模型中,仅发现孕激素受体表达、二倍体DNA含量和无淋巴结转移与高h-MAM表达独立相关。
与乳腺珠蛋白表达相关的所有特征无一例外地反映了侵袭性较低的肿瘤表型。需要进一步研究以阐明这是归因于h-MAM表达本身,还是归因于乳腺珠蛋白表达所构成的另一种机制。