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Erschienen in: Medical Oncology 2/2011

01.06.2011 | Original Paper

EpCAM-autoantibody levels in the course of disease of ovarian cancer patients

verfasst von: Martin Heubner, Dino Errico, Sabine Kasimir-Bauer, Dorothee Herlyn, Rainer Kimmig, Pauline Wimberger

Erschienen in: Medical Oncology | Ausgabe 2/2011

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Abstract

EpCAM is a tumor-associated antigen, which is frequently expressed in ovarian cancer. Recently, autoantibodies against EpCAM have been identified in patients with ovarian cancer. It is not clear whether these autoantibodies are of prognostic importance. We evaluated whether EpCAM-autoantibodies have an impact on the clinical course of patients with ovarian cancer. EpCAM-autoantibodies were determined in sera of 28 healthy voluntary age-matched women and 84 patients with primary epithelial ovarian cancer before and after platinum-based chemotherapy using a recombinant EpCAM-protein for antibody detection by ELISA technique. The median follow-up time was 18 months. Samples exceeding the mean antibody titer of healthy controls plus 2 standard deviations were considered positive. The antibody titer of healthy controls was 0.061 ± 0.015. Using a cut-off value of 0.091, we found 3/84 (4%) patients before and 12/61 (20%) patients with ovarian cancer to be positive for EpCAM-autoantibodies after first-line treatment. Using the paired T-Test, we noted a significant post-therapeutic increase of AABs (P < 0.0001). Notably, AAB-levels after first-line therapy were found to be correlated with the tumor resection status in primary surgery. Analysis of progression-free survival, FIGO stage, grading, age and sensitivity to platinum-based chemotherapy did not reveal significant associations with EpCAM-AAB titers. We observed an increase in AAB-levels during the first-line treatment of patients with ovarian cancer. EpCAM-AAB-levels after first-line treatment appear to correlate with macroscopic tumor residuals after initial surgery.
Literatur
1.
Zurück zum Zitat Goodman MT, et al. Incidence of ovarian cancer by race and ethnicity in the United States, 1992–1997. Cancer. 2003;97(10 Suppl):2676–85.PubMedCrossRef Goodman MT, et al. Incidence of ovarian cancer by race and ethnicity in the United States, 1992–1997. Cancer. 2003;97(10 Suppl):2676–85.PubMedCrossRef
2.
Zurück zum Zitat Litvinov SV, Velders MP, Bakker HA, Fleuren GJ, Warnaar SO. Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule. J Cell Biol. 1994;125(2):437–46.PubMedCrossRef Litvinov SV, Velders MP, Bakker HA, Fleuren GJ, Warnaar SO. Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule. J Cell Biol. 1994;125(2):437–46.PubMedCrossRef
3.
Zurück zum Zitat Momburg F, Moldenhauer G, Hammerling GJ, Moller P. Immunohistochemical study of the expression of a Mr 34,000 human epithelium-specific surface glycoprotein in normal and malignant tissues. Cancer Res. 1987;47(11):2883–91.PubMed Momburg F, Moldenhauer G, Hammerling GJ, Moller P. Immunohistochemical study of the expression of a Mr 34,000 human epithelium-specific surface glycoprotein in normal and malignant tissues. Cancer Res. 1987;47(11):2883–91.PubMed
4.
Zurück zum Zitat Maetzel D, et al. Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol. 2009;11(2):162–71.PubMedCrossRef Maetzel D, et al. Nuclear signalling by tumour-associated antigen EpCAM. Nat Cell Biol. 2009;11(2):162–71.PubMedCrossRef
5.
Zurück zum Zitat Munz M, et al. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene. 2004;23(34):5748–58.PubMedCrossRef Munz M, et al. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. Oncogene. 2004;23(34):5748–58.PubMedCrossRef
6.
Zurück zum Zitat Litvinov SV, et al. Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins. J Cell Biol. 1997;139(5):1337–48.PubMedCrossRef Litvinov SV, et al. Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins. J Cell Biol. 1997;139(5):1337–48.PubMedCrossRef
7.
Zurück zum Zitat Winter MJ, Nagtegaal ID, van Krieken JH, Litvinov SV. The epithelial cell adhesion molecule (Ep-CAM) as a morphoregulatory molecule is a tool in surgical pathology. Am J Pathol. 2003;163(6):2139–48.PubMedCrossRef Winter MJ, Nagtegaal ID, van Krieken JH, Litvinov SV. The epithelial cell adhesion molecule (Ep-CAM) as a morphoregulatory molecule is a tool in surgical pathology. Am J Pathol. 2003;163(6):2139–48.PubMedCrossRef
8.
Zurück zum Zitat Burges A, et al. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. Clin Cancer Res. 2007;13(13):3899–905.PubMedCrossRef Burges A, et al. Effective relief of malignant ascites in patients with advanced ovarian cancer by a trifunctional anti-EpCAM x anti-CD3 antibody: a phase I/II study. Clin Cancer Res. 2007;13(13):3899–905.PubMedCrossRef
9.
Zurück zum Zitat Mosolits S, et al. Autoantibodies against the tumour-associated antigen GA733–2 in patients with colorectal carcinoma. Cancer Immunol Immunother. 1999;47(6):315–20.PubMedCrossRef Mosolits S, et al. Autoantibodies against the tumour-associated antigen GA733–2 in patients with colorectal carcinoma. Cancer Immunol Immunother. 1999;47(6):315–20.PubMedCrossRef
10.
Zurück zum Zitat Kim JH, et al. Identification of epithelial cell adhesion molecule autoantibody in patients with ovarian cancer. Clin Cancer Res. 2003;9(13):4782–91.PubMed Kim JH, et al. Identification of epithelial cell adhesion molecule autoantibody in patients with ovarian cancer. Clin Cancer Res. 2003;9(13):4782–91.PubMed
11.
Zurück zum Zitat Turk MJ, Wolchok JD, Guevara-Patino JA, Goldberg SM, Houghton AN. Multiple pathways to tumor immunity and concomitant autoimmunity. Immunol Rev. 2002;188:122–35.PubMedCrossRef Turk MJ, Wolchok JD, Guevara-Patino JA, Goldberg SM, Houghton AN. Multiple pathways to tumor immunity and concomitant autoimmunity. Immunol Rev. 2002;188:122–35.PubMedCrossRef
12.
Zurück zum Zitat Marcos CA, et al. The usefulness of new serum tumor markers in head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg. 2009;140(3):375–80.PubMedCrossRef Marcos CA, et al. The usefulness of new serum tumor markers in head and neck squamous cell carcinoma. Otolaryngol Head Neck Surg. 2009;140(3):375–80.PubMedCrossRef
13.
Zurück zum Zitat Gumus E, et al. Association of positive serum anti-p53 antibodies with poor prognosis in bladder cancer patients. Int J Urol. 2004;11(12):1070–7.PubMedCrossRef Gumus E, et al. Association of positive serum anti-p53 antibodies with poor prognosis in bladder cancer patients. Int J Urol. 2004;11(12):1070–7.PubMedCrossRef
14.
Zurück zum Zitat Lee YT, Sheikh KM, Quismorio FP Jr, Friou GJ. Circulating anti-tumor and autoantibodies in breast carcinoma: relationship to stage and prognosis. Breast Cancer Res Treat. 1985;6(1):57–65.PubMedCrossRef Lee YT, Sheikh KM, Quismorio FP Jr, Friou GJ. Circulating anti-tumor and autoantibodies in breast carcinoma: relationship to stage and prognosis. Breast Cancer Res Treat. 1985;6(1):57–65.PubMedCrossRef
15.
Zurück zum Zitat Yamazaki Y, et al. Serum p53 antibodies as a prognostic indicator in oral squamous cell carcinoma. Odontology. 2008;96(1):32–7.PubMedCrossRef Yamazaki Y, et al. Serum p53 antibodies as a prognostic indicator in oral squamous cell carcinoma. Odontology. 2008;96(1):32–7.PubMedCrossRef
16.
Zurück zum Zitat Pfisterer J, et al. The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR. Ann Oncol. 2006;17(10):1568–77.PubMedCrossRef Pfisterer J, et al. The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR. Ann Oncol. 2006;17(10):1568–77.PubMedCrossRef
17.
Zurück zum Zitat Sittler T, et al. Concerted potent humoral immune responses to autoantigens are associated with tumor destruction and favorable clinical outcomes without autoimmunity. Clin Cancer Res. 2008;14(12):3896–905.PubMedCrossRef Sittler T, et al. Concerted potent humoral immune responses to autoantigens are associated with tumor destruction and favorable clinical outcomes without autoimmunity. Clin Cancer Res. 2008;14(12):3896–905.PubMedCrossRef
18.
Zurück zum Zitat Lee KR et al. Surface epithelial-stromal tumours. World Health Organization Classification of Tumours. Tumours of the Breast and Female Genital Organs. Lyon: IARC Press; 2003. pp 117–45. Lee KR et al. Surface epithelial-stromal tumours. World Health Organization Classification of Tumours. Tumours of the Breast and Female Genital Organs. Lyon: IARC Press; 2003. pp 117–45.
19.
Zurück zum Zitat Silverberg SG. Histopathologic grading of ovarian carcinoma: a review and proposal. Int J Gynecol Pathol. 2000;19(1):7–15.PubMedCrossRef Silverberg SG. Histopathologic grading of ovarian carcinoma: a review and proposal. Int J Gynecol Pathol. 2000;19(1):7–15.PubMedCrossRef
20.
Zurück zum Zitat FIGO. Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int J Gynaecol Obstet 2009;105(1):3–4. FIGO. Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int J Gynaecol Obstet 2009;105(1):3–4.
21.
Zurück zum Zitat Strassburg CP, et al. Baculovirus recombinant expressing a secreted form of a transmembrane carcinoma-associated antigen. Cancer Res. 1992;52(4):815–21.PubMed Strassburg CP, et al. Baculovirus recombinant expressing a secreted form of a transmembrane carcinoma-associated antigen. Cancer Res. 1992;52(4):815–21.PubMed
22.
Zurück zum Zitat Abe H, et al. Preparation of recombinant MK-1/Ep-CAM and establishment of an ELISA system for determining soluble MK-1/Ep-CAM levels in sera of cancer patients. J Immunol Methods. 2002;270(2):227–33.PubMed Abe H, et al. Preparation of recombinant MK-1/Ep-CAM and establishment of an ELISA system for determining soluble MK-1/Ep-CAM levels in sera of cancer patients. J Immunol Methods. 2002;270(2):227–33.PubMed
Metadaten
Titel
EpCAM-autoantibody levels in the course of disease of ovarian cancer patients
verfasst von
Martin Heubner
Dino Errico
Sabine Kasimir-Bauer
Dorothee Herlyn
Rainer Kimmig
Pauline Wimberger
Publikationsdatum
01.06.2011
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 2/2011
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9486-3

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