期刊论文详细信息
BMC Research Notes
High EpCAM expression is linked to proliferation and lauren classification in gastric cancer
Nikolas H Stoecklein4  Wolfram T Knoefel4  Olivier Gires1  Stephan E Baldus2  Jan Schulte am Esch4  Stefan A Topp4  Christian Vay4  Andreas Krieg4  Helene Geddert3  Daniel Vallböhmer4  Agnieszka Dulian4  Feride Kroepil4 
[1] Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig-Maximilians-University of Munich, Munich, Germany;Department of Pathology, Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany;Institute of Pathology St. Vincent’s Hospital, Karlsruhe, Germany;Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, Moorenstrasse 5, 40225, Düsseldorf, Germany
关键词: Ki 67;    Overall survival;    Laurén-classification;    EpCAM expression;    Gastric cancer;   
Others  :  1142295
DOI  :  10.1186/1756-0500-6-253
 received in 2012-11-20, accepted in 2013-06-21,  发布年份 2013
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【 摘 要 】

Background

The association of EpCAM expression with the progression of gastric cancer remains unclear. Here, we investigated the expression of EpCAM in gastric cancer subtypes and correlated the data to tumor cell proliferation and clinicopathologic factors.

Methods

The intratumoral expression of EpCAM was assessed in 163 primary gastric cancers (61 diffuse-, 62 intestinal-, 32 mixed-type and 8 unclassified tumors) by immunohistochemistry, using the monoclonal antibody Ber-EP4. Intensity of staining was classified according the HercepTest-score using a standardized scoring system. Ki-67 was used to examine the proliferation in tumor tissue.

Results

Strong EpCAM expression was observed in 77% of the tumors and in 85% of the corresponding lymph nodes. Of the primary tumors, 58% (n=74) presented a homogeneous intratumoral EpCAM expression while 42% were characterised by a heterogenous expression pattern. Tumors with high EpCAM expression at the invasive front were associated with significantly (p=0.03) higher proportion of lymph node metastases and lower median overall survival (p=0.001). Diffuse type tumors presented a significantly higher EpCAM expression at the invasion front compared with the tumor centre (p=0.036). Multivariate survival analysis identified high EpCAM expression at the invasive front as an independent prognostic factor.

We observed a significant (p=0.001) correlation between high EpCAM expression and higher tumor cell proliferation.

Conclusion

High EpCAM expression associates with proliferation and progression of gastric cancer, especially in the diffuse type. Considering the discontenting results of the current adjuvant concepts for gastric cancer patients, EpCAM might be target in the adjuvant therapy of this malignant disease.

【 授权许可】

   
2013 Kroepil et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005, 55:74-108.
  • [2]Jung H, Lee HH, Song KY, Jeon HM, Park CH: Validation of the seventh edition of the american joint committee on cancer TNM staging system for gastric cancer. Cancer 2011, 117(11):2371-2378.
  • [3]Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, et al.: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006, 355:11-20.
  • [4]Balzar M, Winter MJ, de Boer CJ, Litvinov SV: The biology of the 17-1A antigen (Ep-CAM). J Mol Med (Berl) 1999, 77:699-712.
  • [5]Balzar M, Prins FA, Bakker HA, Fleuren GJ, Warnaar SO, Litvinov SV: The structural analysis of adhesions mediated by Ep-CAM. Exp Cell Res 1999, 246:108-121.
  • [6]Maetzel D, Denzel S, Mack B, Canis M, Went P, Benk M, Kieu C, Papior P, Baeuerle PA, Munz M, Gires O: Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol 2009, 11:162-171.
  • [7]Munz M, Zeidler R, Gires O: The tumour-associated antigen EpCAM upregulates the fatty acid binding protein E-FABP. Cancer Lett 2005, 225:151-157.
  • [8]Chaves-Perez A, Mack B, Maetzel D, Kremling H, Eggert C, Harreus U, Gires O: EpCAM regulates cell cycle progression via control of cyclin D1 expression. Oncogene 2013, 32:641-650.
  • [9]van der Gun BT, Melchers LJ, Ruiters MH, de Leij LF, McLaughlin PM, Rots MG: EpCAM in carcinogenesis: the good, the bad or the ugly. Carcinogenesis 2010, 31:1913-1921.
  • [10]Du W, Ji H, Cao S, Wang L, Bai F, Liu J, Fan D: EpCAM: a potential antimetastatic target for gastric cancer. Dig Dis Sci 2010, 55:2165-2171.
  • [11]Baeuerle PA, Gires O: EpCAM (CD326) finding its role in cancer. Br J Cancer 2007, 96:417-423.
  • [12]Seligson DB, Pantuck AJ, Liu X, Huang Y, Horvath S, Bui MH, Han KR, Correa AJ, Eeva M, Tze S, et al.: Epithelial cell adhesion molecule (KSA) expression: pathobiology and its role as an independent predictor of survival in renal cell carcinoma. Clin Cancer Res 2004, 10:2659-2669.
  • [13]Ralhan R, Cao J, Lim T, Macmillan C, Freeman JL, Walfish PG: EpCAM nuclear localization identifies aggressive thyroid cancer and is a marker for poor prognosis. BMC Cancer 2010, 10:331.
  • [14]Dhayat S, Sorescu S, Vallbohmer D, Kraus S, Baldus SE, Rehders A, Kropil F, Krieg A, Knoefel WT, Stoecklein NH: Prognostic significance of EpCAM-positive disseminated tumor cells in rectal cancer patients with stage I disease. Am J Surg Pathol 2012, 36:1809-1816.
  • [15]Went P, Dirnhofer S, Salvisberg T, Amin MB, Lim SD, Diener PA, Moch H: Expression of epithelial cell adhesion molecule (EpCam) in renal epithelial tumors. Am J Surg Pathol 2005, 29:83-88.
  • [16]Balzar M, Winter MJ, de Boer CJ, Litvinov SV: The biology of the 17-1A antigen (Ep-CAM). J Mol Med 1999, 77:699-712.
  • [17]Went P, Vasei M, Bubendorf L, Terracciano L, Tornillo L, Riede U, Kononen J, Simon R, Sauter G, Baeuerle PA: Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers. Br J Cancer 2006, 94:128-135.
  • [18]Songun I, Litvinov SV, van de Velde CJ, Pals ST, Hermans J, van Krieken JH: Loss of Ep-CAM (CO17-1A) expression predicts survival in patients with gastric cancer. Br J Cancer 2005, 92:1767-1772.
  • [19]Wenqi D, Li W, Shanshan C, Bei C, Yafei Z, Feihu B, Jie L, Daiming F: EpCAM is overexpressed in gastric cancer and its downregulation suppresses proliferation of gastric cancer. J Cancer Res Clin Oncol 2009, 135:1277-1285.
  • [20]Gosens MJ, van Kempen LC, van de Velde CJ, van Krieken JH, Nagtegaal ID: Loss of membranous Ep-CAM in budding colorectal carcinoma cells. Mod Pathol 2007, 20:221-232.
  • [21]Joo M, Kim H, Kim MK, Yu HJ, Kim JP: Expression of Ep-CAM in intestinal metaplasia, gastric epithelial dysplasia and gastric adenocarcinoma. J Gastroenterol Hepatol 2005, 20:1039-1045.
  • [22]Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O: The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene 2004, 23:5748-5758.
  • [23]Mueller J, Werner M, Siewert JR: Malignant progression in Barrett’s esophagus: pathology and molecular biology. Recent Results Canc Res 2000, 155:29-41.
  • [24]Strohlein MA, Siegel R, Jager M, Lindhofer H, Jauch KW, Heiss MM: Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis. J Exp Clin Cancer Res 2009, 28:18.
  • [25]Kononen J, Bubendorf L, Kallioniemi A, Barlund M, Schraml P, Leighton S, Torhorst J, Mihatsch MJ, Sauter G, Kallioniemi OP: Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med 1998, 4:844-847.
  • [26]Hofmann M, Stoss O, Shi D, Buttner R, van de Vijver M, Kim W, Ochiai A, Ruschoff J, Henkel T: Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 2008, 52:797-805.
  • [27]Raffel A, Eisenberger CF, Cupisti K, Schott M, Baldus SE, Hoffmann I, Aydin F, Knoefel WT, Stoecklein NH: Increased EpCAM expression in malignant insulinoma: potential clinical implications. Eur J Endocrinol 2010, 162:391-398.
  • [28]Stoecklein NH, Siegmund A, Scheunemann P, Luebke AM, Erbersdobler A, Verde PE, Eisenberger CF, Peiper M, Rehders A, Esch JS, et al.: Ep-CAM expression in squamous cell carcinoma of the esophagus: a potential therapeutic target and prognostic marker. BMC Cancer 2006, 6:165.
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