Summary
The carbohydrate antigen 19-9 (CA19-9) is considered to be of great importance in the diagnosis, differential diagnosis and follow-up of human pancreatic carcinoma. CA19-9 antigen has been isolated and characterized as the oligosaccharide sialylazed lacto-N-fucopentaose II and a monoclonal antibody against CA19-9 is commercially available. In this immunochemical study we have examined the localisation and distribution of monoclonal anti-CA19-9 in pancreatic tissue obtained from 20 patients with a normal pancreas (lacking pancreatic tumour or evidence of inflammation), from 50 patients with chronic pancreatitis and from 50 patients with pancreatic carcinomas of various types. In the normal pancreas (free from tumour or inflammation) we found antiCA19-9 to be localized in the branches of the pancreatic ducts with discontinuities predominantly at the apical surfaces of the lining epithelium. In chronic pancreatitis a continuous positive reaction was found in the small, medium and large ramifications of the pancreatic ducts. In ductal epithelium exhibiting mucoid transformation, a mosaic-like, discontinuous positive reaction was found, whereas in epithelium showing pseudopapillary and papillary hyperplasia a uniform positive reaction was obtained. Multilayered epithelium (“squamous metaplasia”) was negative. The fluid content of any cysts present and the tubular accumulations found in chronic pancreatitis showed a positive reaction. The reaction in chronic pancreatitis differed from that in normal pancreas in its distribution but not in its intensity. All carcinomas of the exocrine pancreas showed intensely positive reaction in a very varied distribution whereas the anaplastic carcinomas gave a negative reaction. Whilst in chronic pancreatitis the binding of anti-CA19-9 was unimpressive and strictly localized, in exocrine pancreatic carcinomas binding was very marked and diffuse in distribution. From this we conclude that malignant cells display a greater number of CA19-9 epitopes than cells in chronic pancreatitis. The difference can only be regarded as quanti tative, since the immunohistochemical reaction does not allow qualitative discrimination between chronic pancreatitis and pancreatic carcinoma; CA19-9 should not be therefore termed a “tumour marker”. The glycoprotein nature of CA19-9 was confirmed by sialidase and chemical desialylation.
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References
Banwo O, Versey J, Hobbs JR (1974) New oncofetal antigen for human pancreas. Lancet 1:643–645
Becker V (1984) Chronische Pankreatitis, klinische Morphologie. G. Thieme Verlag, Stuttgart-New York
Chu TM, Holyoke ED, Douglas HO (1977) Isolation of a glycoprotein antigen from ascites fluid of pancreatic carcinoma. Cancer Res 37:1525–1529
Del Villano BC, Brennan S, Brock P, Bucher C, Liu V, McClure M, Rake B, Space S, Westrick B, Schoemaker H, Zurawski VR, Jr (1983) Radioimmunometric assay for a monoclonal antibody-defined tumour marker CA19-9. Clin Chem 29:549–552
Gelder FB, Reese CJ, Moossa AR, Hall T, Hunter R (1978) Purification, partial characterization and clinical evaluation of a pancreatic oncofetal antigen. Cancer Res 38:313–324
Geyer G, Scheibner Ch (1970) Untersuchungen über die alkalische Hydrolyse von Nukleinsäuren im Gewebeschnitt. IV. Abbaueffekte an Kohlenhydratverbindungen nach verstärkter Hydrolyse. Zugleich ein Beitrag zur Histochemie der Glykokalyx. Acta histochem (Jena)37:148–153
Gupta MK, Arciaga R, Bocci L, Tubbs R, Bukowski R, Deodhar SD (1985) Measurement of monoclonal-antibody-defined antigen (CAl 9-9) in the sera of patients with malignant and nonmalignant diseases. Cancer 56:277–283
Heptner G, Domschke S, Krapf F, Schneider MU, Iro H, Domschke W (1984) Vergleich der Tumormarker CEA and CA19-9 in der kolorektalen Diagnostik. Dtsch Med Wochenschr 109:1309–1312
Heptner G, Domschke S, Schneider MU, Domschke W (1985) Bedeutung des tumorassoziierten Antigens CA19-9 in der Differentialdiagnose von Pankreaserkrankungen. Dtsch Med Wochenschr 110:624–628
Jalanko H, Kuusela P, Roberts P, Sipponen P, Haglund C, Mäkelä O (1984) Comparison of a new tumour marker CA19-9™, with α-fetoprotein and carcinoembryonic antigen in patients with upper gastrointestinal diseases. J Clin Pathol 37:218–222
Klapdor R, Dietel M (1985) Diagnostik und Verlaufskontrolle gastrointestinaler Tumoren mit Tumormarkem Vergleich von CA19-9, CA125 and CEA. In: Klietmann W (ed) Aktuelle Tumormarker. Schattauer Verlag, pp 53–81
Klapdor R, Greten H (1984) Das tumorassoziierte Antigen CA19-9 in der Differentialdiagnostik und Verlaufskontrolle von Malignomen des Pankreas und des Magen-Darm-Traktes. Dtsch Med Wochenschr 109:1935–1939
Klapdor R, Lehmann U, Bahlo M, Greten H, v Ackeren H, Dallek M, Schreiber HW (1983) CA19-9 in der Diagnostik und Differentialdiagnostik des exkretorischen Pankreaskarzinoms. I. Mitt. Tumordiagn Ther 4:197–201
Klapdor R, Klapdor U, Bahlo M, Greten H (1984) CA19-9 in der Diagnostik und Differentialdiagnostik des exkretorischen Pankreaskarzinoms. II. Mitt. Tumordiagn Ther 5:161–165
Klavins JV (1981) Tumor markers of pancreatic carcinoma. Cancer 47:1597–1601
Koprowski H, Steplewski Z, Mitchell K, Herlyn M, Herlyn D, Fuhrer P (1979) Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet 5:957–972
Koprowski H, Steplewski Z, Herlyn M, Sears HF (1981) Specific antigen in serum of patients with colon carcinoma. Science 212:53–55
Kuntz DJ, Archer SJ (1979) Extraction and identification of a human pancreatic-tumor-associated antigen. Oncology 36:134–138
Magnani JL, Nilsson B, Brockhaus M, Zopf D, Steplewski Z, Koprowski H, Ginsburg V (1982) A monoclonal antibody-defined antigen associated with gastrointestinal cancer is a ganglioside containing sialylated lacto-N-fucopentaose. II. J Biol Chem 257:14365–14369
Magnani JL, Steplewski Z, Koprowski H, Ginsburg V (1983) A gastrointestinal and pancreatic cancer-associated antigen in human sera detected by monoclonal antibodies is a mucin. Fed Proc 42:2096
Mihas AA (1978) Immunologic studies on an pancreatic oncofetal protein. J Natl Cancer Inst 60:1439–1444
Quintarelli G, Tsuiki S, Hashimoto Y, Pigman W (1960) Histochemical studies of bovine salivary gland mucins. Biochem Biophys Res Commun 2:423–433
Romhânyi G (1972) Differences in ultrastructural organization of amyloid as revealed by sensitivity or resistance to induced proteolysis. Virchows Arch [Pathol Anat] 357:29–52
Safi M, Büchler B, Schenkluhn B, Berger HG (1984) Diagnostische Bedeutung des Tumormarkers CA19-9 beim Pankreaskarzinom. Dtsch Med Wochenschr 109:1869–1873
Satake K, Kanazawa G, Koh I, Chung YS, Umeyama K (1985) A clinical evaluation of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) in patients with pancreatic carcinoma. J Surg Oncol 29:15–21
Savarino V, Mansi C, Pugliese V, Ferrara GB, Arcuri V, Celle G (1984) Evaluation of a new tumour-associated antigen in pancreatic cancer. Digestion 29:1–4
Schmiegel WH, Kreiker C, Eberl W, Arndt R, Classen M, Greten H, Jessen K, Kalthoff H, Soehendra N, Thiele HG (1985) Monoclonal antibody defined CA19-9 in pancreatic juices and sera. Gut 26:456–460
Schultz DR, Yunis AA (1979) Tumour associated antigen in human pancreatic cancer. J Natl Cancer Inst 62:777–785
Shimano T, Loor RM, Papsidero LD, Kuriyama M, Vincent RG, Nemoto T, Holyoke ED, Berijan R, Douglass HO, Chu TM (1981) Isolation characterization in clinical evaluation of a pancreas cancerassociated antigen. Cancer 47:1602–1613
Staab HJ, Hornung A, Anderer FA, Kieninger G (1984) Klinische Bedeutung des zirkulierenden tumorassoziierten Antigens CA19-9 bei Karzinomen des Verdauungstraktes. Dtsch Med Wochenschr 109:1141–1147
Uhlenbruck G, van Meensel-Maene U, Hanisch FG, Dienst C (1984) Unexpected occurence of the CA19-9 tumour marker in normal human seminal plasma. Hoppe-Seyler’s Z Physiol Chem 365:613–617
Volkholz H, Stolte M, Becker V (1982) Epithelial dysplasias in chronic pancreatitis. Virchows Arch [Pathol Anat] 396:331–349
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Supported by The Wilhelm-Sander-Foundation, Neustadt, Donau
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Makovitzky, J. The distribution and localization of the monoclonal antibody-defined antigen 19-9 (CA19-9) in chronic pancreatitis and pancreatic carcinoma. Virchows Archiv B Cell Pathol 51, 535–544 (1986). https://doi.org/10.1007/BF02899058
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DOI: https://doi.org/10.1007/BF02899058