The Metastasis-Associated Anterior Gradient 2 Protein Is Correlated with Poor Survival of Breast Cancer Patients

被引:77
|
作者
Barraclough, Dong L. [1 ,2 ]
Platt-Higgins, Angela [2 ,3 ,4 ]
Rudland, Suzete de Silva [2 ,3 ,4 ]
Barraclough, Roger [2 ,3 ,4 ]
Winstanley, John [6 ]
West, Christopher R. [5 ]
Rudland, Philip S. [1 ,2 ,3 ,4 ]
机构
[1] Univ Liverpool, Sch Med, Canc Tissue Bank Res Ctr, Liverpool L69 3BX, Merseyside, England
[2] Univ Liverpool, Sch Med, Sch Biol Sci, Liverpool L69 3BX, Merseyside, England
[3] Univ Liverpool, Sch Med, Canc Lab, Liverpool L69 3BX, Merseyside, England
[4] Univ Liverpool, Sch Med, Polio Res Fund Lab, Liverpool L69 3BX, Merseyside, England
[5] Univ Liverpool, Sch Med, Div Publ Hlth, Liverpool L69 3BX, Merseyside, England
[6] Royal Bolton Hosp, Bolton, England
来源
AMERICAN JOURNAL OF PATHOLOGY | 2009年 / 175卷 / 05期
关键词
PROGNOSTIC-SIGNIFICANCE; ESTROGEN-RECEPTOR; HUMAN HOMOLOG; S100A4; P9KA; GENE; EXPRESSION; AGR2; OSTEOPONTIN; ANTIGEN; INDUCTION;
D O I
10.2353/ajpath.2009.090246
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
The secreted metastasis-inducing protein, human anterior gradient 2 (AGR2), has been independently reported to be associated with either a reduced or an increased survival of different groups of patients with breast cancer. We now aim to analyze the expression of AGR2 in a third completely independent group of patients using a specific AGR2 monoclonal antibody (mAb). Primary tumors from a group of 315 patients suffering from operable (stage I and 11) breast cancer with 20-years follow-up were immunocytochemically stained with a specific mAb to AGR2 and associations with prognostic factors and patient survival were analyzed. The mAb specifically recognized AGR2 in Western blots, and positive staining for AGR2 was significantly associated with involved lymph nodes and staining for estrogen receptor a, progesterone receptor, and the metastasis-inducing proteins osteopontin, S100P, and S100A4. After 20 years of follow-up, only 26% of patients with AGR2-positive carcinomas survived compared with 96% of those with AGR2 negative carcinomas, with the highly significant difference in median survival times of 68 and >216 months, respectively (P < 0.0001). Cox's multivariate regression analysis showed that staining for AGR2 was one of the most significant independent prognostic indicators, with a corrected relative risk of 9.4. The presence of AGR2 in the primary tumor is therefore a possible prognostic indicator of poor patient outcome in breast cancer. (Am J Pathol 2009, 175:1848-1857; DOI: 10.2353/ajpath.2009.090246)
引用
收藏
页码:1848 / 1857
页数:10
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