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 99m Tc-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