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Blutgruppenantigenexpression in papillären karzinomen der schilddrüse Eine immunhistochemische und klinische studie über das Vorkommen von Lewis-, AB0- und verwandten antigenen

Blood group antigen expression in papillary carcinoma of the thyroid — An immunohistochemical and clinical study on the occurrence of Lewis-, AB0, and derived antigens

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Abstract

Nine monoclonal antibodies, lectin from Ulex europaeus and neuraminidase enzyme were employed to demonstrate the occurrence of type 1 and type 2 blood group antigens in 104 cases of papillary carcinoma of the thyroid. The reagents applied, recognize the following blood group related antigens: CA-50 (sialylated type 1 precursor), CA-19-9 (sialylated Lea), Lea, Leb, A, B, H, Lex, sialylated Lex, and Ley.

Immunohistochemical studies revealed that papillary carcinoma of the thyroid, in contrast to histologically normal thyroid tissue, is characterised by a progressive expression of blood group antigens. Most tumours (84%) reacted with C-50 antibody, whereas only a minority of the tissues demonstrated the CA-19-9 antigen (38%). Type 2 structures Lex (47%) and Ley (13%) were found less often than their corresponding type 1 isomers Lea (71%) and Leb (62%). Desialylation with neuraminidase increased the Lea and Lex staining intensity in 27 and 44 cases, respectively. of the A, B, H antigens the A determinants encountered most frequently (24%).

Comparative examinations of sequential sections of the same tumour revealed coexpression of type 1 antigens in the same areas. In carcinomas showing type 1 and type 2 antigen reactivity, a complementary distribution of the structures in different tumour areas was often demonstrated. Some tumours presented combined type 1 and type 2 antigen expression in the same cells, however, in distinct areas within the cell.

A follow-up examination was carried out in 68 of the 104 cases. The observation time ranged from 12 to 217 months. Thirteen patients suffered from recurrence, of which 7 died. While lymphatic metastases occurred in 39 tumours, distant metastases were detected in 6 patients. Most of the recurrences were found in patients with tumour classification pT4 (n=19), whereas none of the pT1 carcinomas (n=20) showed recurrence.

The clinical results were compared to the blood group antigen expression results. There was no correlation between antigen expression and differentiation degree of the tumour. The pT4 tumours showed a significant higher expression of the CA-50, CA-19-9, Lea and Sialyl Lex structures. Carcinomas expressing the Ley antigen were associated with a significant higher level of metastasizing capacity. The Ley, H type 1 and H type 2 antigens occurred more frequently in recurrent tumours (n=14). In contrast, none of the patients whose carcinomas expressed the Aantigens (n=14) suffered from a recurrence or hematogenous metastasis.

Multiple stepwise regression analysis was carried out to check the importance of each staining and clinical factor. In this analysis, ‘distant metastasis’ was the most important parameter, whereas the staining results were of minor statistical importance.

Zusammenfassung

In einer immunhistochemischen Arbeit wurden 104 papilläre Schilddrüsenkarzinome auf das Vorkommen von Blutgruppenantigenen des AB0- und Lewis-Systems sowie verwandter, tumorassoziierter Antigene mit Typ-1- und Typ-2-Grundstruktur untersucht. Folgende Strukturen wurden im Gewebe nachgewiesen: CA-50 (sialinierter Typ-1-Vorläufer), CA-19-9 (Sialyl-Lea), Lea, Leb, A, B, H, Lex, Sialyl-Lex und Ley. Während gesundes, adultes Schilddrüsengewebe keine Blutgruppenantigene exprimierte, waren die papillären Karzinome durch die progressive Expression dieser Strukturen gekennzeichnet. Die meisten Tumoren reagierten mit dem C-50-Antikörper (84%), während deutlich weniger Gewebe das CA-19-9-Antigen aufwiesen (38%). Die Typ-2-Strukturen Lex (47%) und Ley (13%) wurden deutlich seltener gefunden als die korrespondierenden Typ-1-Antigene Lea (71%) und Leb (62%). Die Vorbehandlung mit Neuraminidase verstärkte die Lea- und Lex-Färbeergebnisse in 27 bzw. 44 Fällen. Von den A-, B-, und H-Antigenen wurden die A-Determinanten am häufigsten nachgewiesen (24%). In vergleichenden Untersuchungen von Serienschnitten der gleichen Tumoren wurde eine Koexpression mehrerer Typ-1-Antigene im denselben Tumorarealen festgestellt. Karzinome mit Expression von Typ-1- und Typ-2-Strukturen wiesen häufig eine komplementäre Antigenexpression in verschiedenen Bereichen der Gewebe auf. Einige Tumoren exprimierten Typ-1- und Typ-2-Strukturen auch in den gleichen Zellen, jedoch in verschiedenen Bereichen der jeweiligen Zellen.

In 68 Fällen wurde eine Follow-up-Untersuchung durchgeführt. Die Beobachtungszeiträume lagen zwischen 12 und 217 Monaten. In 13 Fällen rezidivierte der Tumor, 7 dieser Patienten verstarben an dem Tumorleiden. Die meisten Rezidive traten bei Patienten auf, deren Tumoren die Grenzen des Organs überschritten hatten (pT4, n=19), während keines der pT1-Karzinome (n=20) zu einem Rezidiv geführt hatte. Während Lymphknotenmetastasen in 39 Fällen auftraten, wiesen 6 Patienten Fernmetastasen auf. Die klinischen Ergebnisse wurden mit den Färbeergebnissen korreliert. Es bestand kein Zusammenhang zwischen Antigenexpression und Tumordifferenzierung. Die pT4-Tumoren zeigten eine signifikant stärkere Expression der CA-50-, CA-19-9-, Lea und Sialyl-Lex-Strukturen. Karzinome mit Ley-Expression wiesen signifikant häufiger Metastasen auf. Ley, H-Typ-1 und H-Typ-2 traten häufiger in rezidivierenden Tumoren auf. Im Gegensatz dazu waren alle Patienten, deren Karzinom das A-Antigen exprimierte, fernmetastasen- und rezidivfrei (n=14). In der multiplen Regressionsanalyse wies der Faktor Fernmetastasierung die größte prognostische Relevanz auf, während im Vergleich dazu die Färbeergebnisse statistisch von untergeordneter Bedeutung waren.

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Authors and Affiliations

  1. Abteilung für Allgemein-, Gefäß- und Thoraxchirurgie, Allgemeines Krankenhaus Harburg, D-21075, Hamburg

    A. Larena

  2. Institut für Pathologie, Allgemeines Krankenhaus St. Georg, Hamburg

    M. Vierbuchen

  3. Institut für Pathologie, Universität Zürich, Schweiz

    S. Schröder

  4. Abeilung für Chirurgie, St. Katharinen Hospital, Frechen

    A. Larena-Avellaneda

  5. Institut für Dermatologie, Universitätsklinik Hamburg-Eppendorf, Germany

    I. Hadshiew

  6. Institut für Pathologie, Universität Köln, Mit Unterstützung der DFG Vi 106/1-2, Germany

    R. Fischer

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Larena, A., Vierbuchen, M., Schröder, S. et al. Blutgruppenantigenexpression in papillären karzinomen der schilddrüse Eine immunhistochemische und klinische studie über das Vorkommen von Lewis-, AB0- und verwandten antigenen. Langenbecks Arch Chir 381, 102–113 (1996). https://doi.org/10.1007/BF00183940

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