Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1998 Jun;152(6):1401–1406.

Dysregulated expression of CD66a (BGP, C-CAM), an adhesion molecule of the CEA family, in endometrial cancer.

A M Bamberger 1, L Riethdorf 1, P Nollau 1, M Naumann 1, I Erdmann 1, J Götze 1, J Brümmer 1, H M Schulte 1, C Wagener 1, T Löning 1
PMCID: PMC1858433  PMID: 9626043

Abstract

CD66a (BGP, C-CAM) is an adhesion molecule of the carcinoembryonic antigen family that has been shown to be down-regulated in colorectal, prostate, and breast cancers. The purpose of the present study was to determine its expression pattern in the normal human endometrium and in endometrial neoplasia. For this purpose, we performed immunohistochemistry using the 4D1/C2 monoclonal antibody on a series of 24 normal endometrial samples and 47 endometrial carcinomas. Strong CD66a expression was observed in glandular and luminal epithelial cells of the normal endometrium with a consistent localization at the apical poles of these cells throughout the cycle. In late secretory (premenstrual) phase, loss of cellular polarity resulted in a membranous expression pattern in some glandular cells. In the analyzed tumor samples increasing areas with a complete loss of expression were observed with increasing malignancy grade. The apical expression pattern of the normal epithelium was changed to a membranous all-around pattern in 55% of the tumors, mostly in solid areas. This change correlated with malignancy grade and could be observed in 3 of 15 G1 tumors, 4 of 12 G2 tumors, 11 of 12 G3 tumors, and 8 of 8 serous-papillary carcinomas. Areas with membranous expression pattern could be observed along with areas with a normal apical expression pattern in lower grade carcinomas and with areas with complete loss of expression in high grade tumors. Northern blot analysis showed a loss of mRNA expression in tumor samples and HEC-1B endometrial adenocarcinoma cells. Loss of protein expression in the tumor samples was also observed by Western blot. In conclusion, CD66a protein expression is dysregulated in endometrial carcinomas, showing reduction or loss of expression with increasing malignancy grade and a change from the apical to a membranous localization.

Full text

PDF
1401

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aurivillius M., Hansen O. C., Lazrek M. B., Bock E., Obrink B. The cell adhesion molecule Cell-CAM 105 is an ecto-ATPase and a member of the immunoglobulin superfamily. FEBS Lett. 1990 May 21;264(2):267–269. doi: 10.1016/0014-5793(90)80264-j. [DOI] [PubMed] [Google Scholar]
  2. Barnett T. R., Kretschmer A., Austen D. A., Goebel S. J., Hart J. T., Elting J. J., Kamarck M. E. Carcinoembryonic antigens: alternative splicing accounts for the multiple mRNAs that code for novel members of the carcinoembryonic antigen family. J Cell Biol. 1989 Feb;108(2):267–276. doi: 10.1083/jcb.108.2.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brümmer J., Neumaier M., Göpfert C., Wagener C. Association of pp60c-src with biliary glycoprotein (CD66a), an adhesion molecule of the carcinoembryonic antigen family downregulated in colorectal carcinomas. Oncogene. 1995 Oct 19;11(8):1649–1655. [PubMed] [Google Scholar]
  4. Drzeniek Z., Lamerz R., Fenger U., Wagener C., Haubeck H. D. Identification of membrane antigens in granulocytes and colonic carcinoma cells by a monoclonal antibody specific for biliary glycoprotein, a member of the carcinoembryonic antigen family. Cancer Lett. 1991 Feb;56(2):173–179. doi: 10.1016/0304-3835(91)90093-w. [DOI] [PubMed] [Google Scholar]
  5. Hinoda Y., Neumaier M., Hefta S. A., Drzeniek Z., Wagener C., Shively L., Hefta L. J., Shively J. E., Paxton R. J. Molecular cloning of a cDNA coding biliary glycoprotein I: primary structure of a glycoprotein immunologically crossreactive with carcinoembryonic antigen. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6959–6963. doi: 10.1073/pnas.85.18.6959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hsieh J. T., Luo W., Song W., Wang Y., Kleinerman D. I., Van N. T., Lin S. H. Tumor suppressive role of an androgen-regulated epithelial cell adhesion molecule (C-CAM) in prostate carcinoma cell revealed by sense and antisense approaches. Cancer Res. 1995 Jan 1;55(1):190–197. [PubMed] [Google Scholar]
  7. Kuijpers T. W., Hoogerwerf M., van der Laan L. J., Nagel G., van der Schoot C. E., Grunert F., Roos D. CD66 nonspecific cross-reacting antigens are involved in neutrophil adherence to cytokine-activated endothelial cells. J Cell Biol. 1992 Jul;118(2):457–466. doi: 10.1083/jcb.118.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kunath T., Ordoñez-Garcia C., Turbide C., Beauchemin N. Inhibition of colonic tumor cell growth by biliary glycoprotein. Oncogene. 1995 Dec 7;11(11):2375–2382. [PubMed] [Google Scholar]
  9. Lin S. H., Guidotti G. Cloning and expression of a cDNA coding for a rat liver plasma membrane ecto-ATPase. The primary structure of the ecto-ATPase is similar to that of the human biliary glycoprotein I. J Biol Chem. 1989 Aug 25;264(24):14408–14414. [PubMed] [Google Scholar]
  10. Luo W., Wood C. G., Earley K., Hung M. C., Lin S. H. Suppression of tumorigenicity of breast cancer cells by an epithelial cell adhesion molecule (C-CAM1): the adhesion and growth suppression are mediated by different domains. Oncogene. 1997 Apr 10;14(14):1697–1704. doi: 10.1038/sj.onc.1200999. [DOI] [PubMed] [Google Scholar]
  11. Neumaier M., Paululat S., Chan A., Matthaes P., Wagener C. Biliary glycoprotein, a potential human cell adhesion molecule, is down-regulated in colorectal carcinomas. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10744–10748. doi: 10.1073/pnas.90.22.10744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nollau P., Scheller H., Kona-Horstmann M., Rohde S., Hagenmüller F., Wagener C., Neumaier M. Expression of CD66a (human C-CAM) and other members of the carcinoembryonic antigen gene family of adhesion molecules in human colorectal adenomas. Cancer Res. 1997 Jun 15;57(12):2354–2357. [PubMed] [Google Scholar]
  13. Prall F., Nollau P., Neumaier M., Haubeck H. D., Drzeniek Z., Helmchen U., Löning T., Wagener C. CD66a (BGP), an adhesion molecule of the carcinoembryonic antigen family, is expressed in epithelium, endothelium, and myeloid cells in a wide range of normal human tissues. J Histochem Cytochem. 1996 Jan;44(1):35–41. doi: 10.1177/44.1.8543780. [DOI] [PubMed] [Google Scholar]
  14. Riethdorf L., Lisboa B. W., Henkel U., Naumann M., Wagener C., Löning T. Differential expression of CD66a (BGP), a cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant, and malignant lesions of the human mammary gland. J Histochem Cytochem. 1997 Jul;45(7):957–963. doi: 10.1177/002215549704500705. [DOI] [PubMed] [Google Scholar]
  15. Rojas M., Fuks A., Stanners C. P. Biliary glycoprotein, a member of the immunoglobulin supergene family, functions in vitro as a Ca2(+)-dependent intercellular adhesion molecule. Cell Growth Differ. 1990 Nov;1(11):527–533. [PubMed] [Google Scholar]
  16. Stoffel A., Neumaier M., Gaida F. J., Fenger U., Drzeniek Z., Haubeck H. D., Wagener C. Monoclonal, anti-domain and anti-peptide antibodies assign the molecular weight 160,000 granulocyte membrane antigen of the CD66 cluster to a mRNA species encoded by the biliary glycoprotein gene, a member of the carcinoembryonic antigen gene family. J Immunol. 1993 Jun 1;150(11):4978–4984. [PubMed] [Google Scholar]
  17. Svalander P. C., Odin P., Nilsson B. O., Obrink B. Expression of cellCAM-105 in the apical surface of rat uterine epithelium is controlled by ovarian steroid hormones. J Reprod Fertil. 1990 Jan;88(1):213–221. doi: 10.1530/jrf.0.0880213. [DOI] [PubMed] [Google Scholar]
  18. Thompson J. A., Grunert F., Zimmermann W. Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. J Clin Lab Anal. 1991;5(5):344–366. doi: 10.1002/jcla.1860050510. [DOI] [PubMed] [Google Scholar]
  19. Turbide C., Rojas M., Stanners C. P., Beauchemin N. A mouse carcinoembryonic antigen gene family member is a calcium-dependent cell adhesion molecule. J Biol Chem. 1991 Jan 5;266(1):309–315. [PubMed] [Google Scholar]
  20. Zhang L., Zhou W., Velculescu V. E., Kern S. E., Hruban R. H., Hamilton S. R., Vogelstein B., Kinzler K. W. Gene expression profiles in normal and cancer cells. Science. 1997 May 23;276(5316):1268–1272. doi: 10.1126/science.276.5316.1268. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES