Endoscopy 2002; 34(10): 801-807
DOI: 10.1055/s-2002-34254
Original Article
© Georg Thieme Verlag Stuttgart · New York

Fluorescence Endoscopy Using a Fluorescein-Labeled Monoclonal Antibody Against Carcinoembryonic Antigen in Patients with Colorectal Carcinoma and Adenoma

R.  Keller1 , G.  Winde1 , H.  J.  Terpe1 , E.  C.  Foerster1 , W.  Domschke1
  • 1Department of Medicine B, University of Münster, Münster, Germany
Further Information

Publication History

Submitted: 27 January 2002

Accepted after Revision: 16 April 2002

Publication Date:
23 September 2002 (online)

Background and Study Aims: Various methods of fluorescence excitation and detection have been developed in gastrointestinal endoscopy. This study reports an endoscopic technique using locally applied fluorescein-labeled antibodies for in-vivo detection of colorectal dysplasia and carcinoma.
Patients and Methods: Fluorescence endoscopy with a fluorescein-labeled monoclonal antibody against carcinoembryonic antigen (CEA) was carried out in 27 patients with colonic polypoid lesions. During conventional colonoscopy, the monoclonal antibody was applied directly onto the mucosal surface. After an incubation time of 10 min, specific fluorescence was visualized with a conventional endoscope whose optical range was increased via two narrow-band filters.
Results: Fluorescence in vivo was present in 19 out of 25 carcinomas and in three of eight adenomas. The technique failed in the presence of mucosal ulceration or bleeding. One fluorescence-positive villous adenoma showed high-grade dysplasia, and another fluorescence-positive polypoid lesion was diagnosed as carcinoma in adenoma. Normal-appearing mucosa was fluorescence-negative in all cases. Endoscopic fluorescence significantly correlated with the CEA expression of luminal epithelial cells as determined immunohistochemically (Wilcoxon-Mann-Whitney U-test, P < 0.01). In all cases without ulceration or bleeding, the specificity of fluorescence endoscopy was 100 %, the sensitivity was 78.6 %, and the accuracy was 89.3 %.
Conclusions: Fluorescence endoscopy using fluorescein-labeled monoclonal antibody against CEA was shown to be positive in most cancers and some adenomas. Further and larger studies will be needed to demonstrate the value of this technique for differential diagnosis.

References

  • 1 Silverberg E, Lubera J A. Cancer statistics.  CA Cancer J Clin. 1989;  39 3-20
  • 2 Winawer S J, Zauber A G, Stewart E, O’Brien M J. The natural history of colorectal cancer: Opportunities for intervention.  Cancer. 1991;  67 1143-1149
  • 3 Acosta M M, Boyce H W . Chromoendoscopy: Where is it useful?.  J Clin Gastroenterol. 1998;  27 13-20
  • 4 Zonios G I, Cothren R M, Arendt J T. et al . Morphological models of human colon tissue fluorescence.  IEEE Trans Biomed Eng. 1996;  43 113-121
  • 5 Kapadia C R, Cutruzzola F W, O’Brien K M. et al . Laser-induced fluorescence spectroscopy of human colonic mucosa.  Gastroenterology. 1990;  99 150-157
  • 6 Wang T D, van Dam J, Crawford J M. et al . Fluorescence endoscopic imaging of human colonic adenomas.  Gastroenterology. 1996;  111 1182-1191
  • 7 Cothren R M, Sivak M V, van Dam J. et al . Detection of dysplasia at colonoscopy using laser-induced fluorescence: A blinded study.  Gastrointest Endosc. 1996;  44 168-176
  • 8 Schomacker K T, Frisoli J K, Compton C C. et al . Ultraviolet laser-induced fluorescence of colonic polyps.  Gastroenterology. 1992;  102 1155-1160
  • 9 Brand S, Stepp H, Ochsenkühn T. et al . Detection of colonic dysplasia by light-induced fluorescence endoscopy: A pilot study.  Int J Colorect Dis. 1999;  14 63-68
  • 10 Messmann H, Knüchel R, Bäumler W. et al . Endoscopic fluorescence detection in patients with Barrett’s esophagus, ulcerative colitis, or adenomatous polyps after 5-aminolevulinic acid-induced protoporphyrin IX sensitization.  Gastrointest Endosc. 1999;  49 97-101
  • 11 Muguruma N, Ito S, Hayashi S. et al . Antibodies labeled with fluorescence-agent excitable by infrared rays.  J Gastroenterol. 1998;  33 467-471
  • 12 Keller R, Winde G, Eisenhawer C. et al . Immunoscopy: A technique combining endoscopy and immunofluorescence for diagnosis of colorectal carcinoma.  Gastrointest Endosc. 1998;  47 154-161
  • 13 Isaacson P, Le V ann. The demonstration of carcinoembryonic antigen in colorectal carcinoma and colonic polyps using an immunoperoxidase technique.  Cancer. 1976;  38 1348-1356
  • 14 Pèlegrin A, Folli S, Buchegger F. et al . Antibody-fluorescein conjugates for photoimmunodiagnosis of human colon carcinoma in nude mice.  Cancer. 1991;  67 2529-2537
  • 15 Jass J R, Sobin L H. Histological typing of intestinal tumors. 2nd edn. Berlin; Springer 1989
  • 16 Fischbach W, Zidianakis Z, Lüke G. et al . DNA mapping of colorectal neoplasms: A flow cytometric study of DNA abnormalities and proliferation.  Gastroenterology. 1993;  105 1126-1133
  • 17 Marshall J B, Diaz-Arias A A, Barthel J S. et al . Prospective evaluation of optimal number of biopsy specimens and brush cytology in the diagnosis of the colorectum.  Am J Gastroenterol. 1993;  88 1352-1354
  • 18 Takenoshita S I, Hashizume T, Asao T. et al . Immunoscintigraphy using 99mTc-labeled anti-CEA monoclonal antibody for patients with colorectal cancer.  Anticancer Res. 1995;  15 471-476
  • 19 Goldenberg D M, Larson S M. Radioimmunodetection in cancer identification.  J Nucl Med. 1992;  33 803-814
  • 20 Goldenberg D M, Larson S M, Reisfeld R A, Schlom J. Targeting cancer with radiolabeled antibodies.  Immunol Today. 1995;  16 261-264
  • 21 Bodey B, Siegel S E, Kaiser H E. Human cancer detection and immunotherapy with conjugated and non-conjugated monoclonal antibodies.  Anticancer Res. 1996;  16 661-674
  • 22 Ballou B, Fisher G W, Waggoner A S. et al . Tumor labeling in vivo using cyanine-conjugated monoclonal antibodies.  Cancer Immunol Immunother. 1995;  41 257-263
  • 23 Folli S, Wagnière G, Pelegrin A. et al . Immunophotodiagnosis of colon carcinomas in patients injected with fluoresceinated chimeric antibodies against carcinoembryonic antigen.  Proc Natl Acad Sci USA. 1992;  89 7973-7977
  • 24 Trauner M, Grygar S, Strauber R E. et al . Carcinoembryonic antigen, cytokeratin expression and mucin composition in hyperplastic and neoplastic polyps of the colorectum.  Z Gastroenterol. 1994;  32 626-631
  • 25 Goldenberg D M, Keshab D P, Dahlman H L. Antigens associated with normal and malignant gastrointestinal tissues.  Cancer Res. 1976;  36 3455-3463
  • 26 Burtin P, von Kleist S, King M. Immunohistological localization of carcinoembryonic antigen and nonspecific cross-reacting antigen in gastrointestinal normal and tumoral tissues.  Cancer Res. 1973;  33 3299-3305
  • 27 Fischbach W, Mössner J. Tissue concentrations of CEA and CA 19-9 in the carcinogenesis of colorectal carcinoma exemplified by the adenoma-carcinoma sequence.  Res Exp Med. 1988;  188 101-114
  • 28 Fischbach W, Mössner J, Seyschab H, Höhn H. Tissue carcinoembryonic antigen and DNA aneuploidy in precancerous and cancerous colorectal lesions.  Cancer. 1990;  65 1820-1824
  • 29 Reintgen D S, Shimizu K, Coleman E. et al . Immunodiagnosis of tumors in vivo using radiolabeled antibody A2B5.  J Surg Oncol. 1983;  23 205-211
  • 30 Ballou B, Jaffe R, Taylor R J. et al . Tumor radioimmunolocation: Different antibody retention by antigenic normal tissue and tumor.  J Immunol. 1984;  132 2111-2116

R. Keller, M.D.

Dept. of Medicine II · Aschaffenburg Hospital · Academic Hospital of the University of Würzburg

Am Hasenkopf · 63739 Aschaffenburg · Germany ·

Fax: + 49-6021-323031

Email: dr.r.keller@t-onine.de

    >