Epithelial cell adhesion molecule (EpCAM) is overexpressed in breast cancer metastases

被引:73
作者
Cimino, Ashley [1 ]
Halushka, Marc [1 ]
Illei, Peter [1 ]
Wu, Xinyan [2 ]
Sukumar, Saraswati [2 ]
Argani, Pedram [1 ,2 ]
机构
[1] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21231 USA
[2] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA
关键词
Metastasis; EpCAM; Breast; Carcinoma; EP-CAM; THERAPEUTIC TARGET; ANTIGEN EPCAM; BONE-MARROW; EXPRESSION; HETEROGENEITY; TUMORS;
D O I
10.1007/s10549-009-0671-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
EpCAM (CD326) has diverse roles in cell adhesion and proliferation, and is known to be overexpressed in primary breast carcinomas (PBCs). While clinical and preclinical data suggest a role for EpCAM in metastases, the only prior study of EpCAM expression in breast cancer metastases suggested that EpCAM expression is decreased after first-line chemotherapy. This study evaluates EpCAM expression in metastatic breast carcinoma (MBC) versus matched PBC. Rapid autopsies were performed on 17 patients with widely metastatic breast cancer. Single patient tissue microarrays (TMAs) were constructed from archived PBC and post-mortem MBCs. In total, 169 spots from 17 PBCs and 895 spots from 195 MBCs were labeled for EpCAM by immunohistochemistry (IHC). Expression was scored as intensity (1-3) multiplied by percent membrane labeling (0-100%) and was sub-classified as low (0-100), moderate (101-200), or high (201-300) labeling. PBCs exhibited exclusively low-moderate EpCAM labeling. EpCAM labeling was present in all metastases and was significantly increased in MBCs of 14 of 17 patients (P value range <0.05 to <0.0001, t test). In the remaining three patients, EpCAM labeling was non-significantly increased in 1 and unchanged in 2. High EpCAM labeling was verified using a different antibody for IHC, as well as in a separate series of surgically resected metastases compared to unmatched surgically resected primary breast cancers. In conclusion, EpCAM is highly expressed in MBCs compared to matched PBCs, verifying that it is a promising therapeutic target.
引用
收藏
页码:701 / 708
页数:8
相关论文
共 22 条
  • [1] EpCAM - A new therapeutic target for an old cancer antigen
    Armstrong, A
    Eck, SL
    [J]. CANCER BIOLOGY & THERAPY, 2003, 2 (04) : 320 - 325
  • [2] EpCAM (CD326) finding its role in cancer
    Baeuerle, P. A.
    Gires, O.
    [J]. BRITISH JOURNAL OF CANCER, 2007, 96 (03) : 417 - 423
  • [3] Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype
    Balic, Marija
    Lin, Henry
    Young, Lillian
    Hawes, Debra
    Giuliano, Armando
    McNamara, George
    Datar, Ram H.
    Cote, Richard J.
    [J]. CLINICAL CANCER RESEARCH, 2006, 12 (19) : 5615 - 5621
  • [4] Braun S, 1999, CLIN CANCER RES, V5, P3999
  • [5] Molecular Origins of Cancer Molecular Basis of Metastasis
    Chiang, Anne C.
    Massague, Joan
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (26) : 2814 - 2823
  • [6] Ep-CAM overexpression in breast cancer as a predictor of survival
    Gastl, G
    Spizzo, G
    Obrist, P
    Dünser, M
    Mikuz, G
    [J]. LANCET, 2000, 356 (9246) : 1981 - 1982
  • [7] Loss of membranous Ep-CAM in budding colorectal carcinoma cells
    Gosens, Marleen J. E. M.
    van Kempen, Leon C. L.
    van de Velde, Cornelis J. H.
    van Krieken, J. Han J. M.
    Nagtegaal, Iris D.
    [J]. MODERN PATHOLOGY, 2007, 20 (02) : 221 - 232
  • [8] Epithelial glycoprotein-2 expression is subject to regulatory processes in epithelial-mesenchymal transitions during metastases: an investigation of human cancers transplanted into severe combined immunodeficient mice
    Jojovic, M
    Adam, E
    Zangemeister-Wittke, U
    Schumacher, U
    [J]. HISTOCHEMICAL JOURNAL, 1998, 30 (10): : 723 - 729
  • [9] Cancer - The metastasis cascade
    Klein, Christoph A.
    [J]. SCIENCE, 2008, 321 (5897) : 1785 - 1787
  • [10] Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins
    Litvinov, SV
    Balzar, M
    Winter, MJ
    Bakker, HAM
    BriairedeBruijn, I
    Prins, F
    Fleuren, GJ
    Warnaar, SO
    [J]. JOURNAL OF CELL BIOLOGY, 1997, 139 (05) : 1337 - 1348