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MHC class I and II antigen expression and interferon α treatment of human midgut carcinoid tumors

  • International Association of Endocrine Surgeons—Manuscripts Presented at the 35th World Congress of the International Society of Surgery, Hong Kong, August 1993
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Abstract

Cryosections of 28 primary and metastatic midgut carcinoid tumors from 12 patients with carcinoid syndrome were investigated immunohistochemically with antibodies that recognize human MHC class I (HLA-ABC) and class II (HLA-DR) antigens. The tumor parenchyma of all six patients treated with interferon α (IFN-α) during a mean 8.6 months (3x106 to 5x106 U three times weekly) exhibited unequivocal HLA-ABC immunoreactivity, with only minor discrepancies between primary lesions and metastases in mesenteric lymph nodes and liver. Class I staining was absent on the tumor cells of all 14 specimens from the patients without IFN therapy but was induced by culturing freshly dispersed tumor cells in vitro for 48 hours in the presence of recombinant IFN-α. The stroma of all neoplasms displayed class I and II immunostaining, as did usually a few CD4-expressing cells. The carcinoid specimens lacked parenchymal HLA-DR immunoreactivity, which is interesting considering suggestions on improved prognosis for bowel carcinomas lacking the class II expression. The study supports the idea that induction of MHC class I antigens could contribute to the beneficial clinical effects of IFN-α treatment in patients with midgut carcinoid tumors.

Résumé

On a recherché la présence d'antigènes MHC classe I (HLA-ABC) et classe II (HLA-DR) par des anticorps correspondants dans la cryosection de 28 tumeurs primitives ou métastatiques carcinoïdes de l'intestin moyen provenant de 12 patients ayant un syndrome carcinoïde. La tumeur parenchymateuse des 6 patients ayant été traités par l'alpha interféron (IFN-a) pendant une moyenne de 8.6 mois (3.5x106 U 3/semaine) avaient une immunoréactivité non équivoque avec seulement des différences mineures entre les lésions primaires et métastatiques au niveau des adénopathies envahies et le foie. La coloration histologique était négative pour les lésions classe I dans les 14 pièces anatomiques provenant des patients n'ayant pas eu de traitement par l'IFN, mais celle-ci a pu être induite, après culture in vitro de cellules tumorales fraîches pendant 48 heures en la présence d'un recombinant IFN-a. Le stroma de tous les néoplasmes présentait une immunocoloration classe I et classe II ainsi qu'une expression CD4 peu prononcée. Les pièces anatomiques de tumeurs carcinoides n'avaient pas d'immunoactivité HLA-DR, ce qui est intéressant compte tenu des hypothèses suggérant un meilleur pronostic pour les patients ayant un cancer du gros intestin sans expression classe II. Cette étude est en faveur d'une action positive complémentaire par l'induction d'antigènes MHC classe I chez les patients porteurs d'une tumeur carcinoïde de l'intestin moyen, traités par l'interféron IFN-a.

Resumen

Las criosecciones de 28 tumores carcinoides primarios y metastásicos del intestino medio provenientes de 12 pacientes con el síndrome carcinoide fueron investigados inmunohisto-químicamente con anticuerpos reconocedores de los antígenos humanos MHC clase I (HLA-ABC) y clase II (HLA-DR).

El parenquima tumoral de todos los 6 pacientes tratados con interferón alfa (IFN-α) durante un tiempo medio de 8.6 meses (3–5x106 U 3x/semana) exhibieron inequívoca inmuno-reactividad HLA-ABC con sólo discrepancias menores entre las lesiones primarias y las metástasis en el hígado y los ganglios mesentéricos.

La coloración de clase I estuvo ausente en las células tumorales de todos los 14 especímenes de los pacientes que no recibieron terapia con IFN, pero se indujo mediante el cultivo de células de dispersión fresca invitro por 48 horas en presencia de IFN-α recombinante. El estroma de todos los neoplasmas demostró coloración clase I y II, así como unas pocas células de expresión CD4. Los especímenes carcinoides estuvieron desprovistos de inmuno-reactividad HLA-DR, lo cual es interesante si se considera la sugerencia de mejor pronóstico en los carcinomas del colon desprovistos de expresión clase II.

Este estudio da apoyo a que la inducción de antígenos MHC clase I puede contribuir a beneficio clínico en el tratamiento con IFN-α de pacientes con tumores carcinoides del intestino medio.

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Authors and Affiliations

  1. Department of Surgery, University Hospital, S-751 85, Uppsala, Sweden

    C. Makridis M.D., C. Juhlin M.D., G. Åkerström M.D. & J. Rastad M.D.

  2. Department of Internal Medicine, University Hospital, S-751 85, Uppsala, Sweden

    K. Öberg M.D.

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  1. C. Makridis M.D.
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  2. C. Juhlin M.D.
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  3. G. Åkerström M.D.
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  4. K. Öberg M.D.
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  5. J. Rastad M.D.
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Makridis, C., Juhlin, C., Åkerström, G. et al. MHC class I and II antigen expression and interferon α treatment of human midgut carcinoid tumors. World J. Surg. 18, 481–486 (1994). https://doi.org/10.1007/BF00353741

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