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Expression of basic fibroblast growth factor in thyroid disorders

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

Morphologic and biologic studies were undertaken to clarify the biologic significance of basic fibroblast growth factor (bFGF) in human thyroid neoplasms. A total of 71 malignant tumors (50 papillary carcinomas, 14 follicular carcinomas, 7 anaplastic carcinomas), 11 follicular adenomas, 6 adenomatous goiters, and 6 Graves' disease tissues were examined employing immunohistochemical methods (avidin-biotin-peroxidase complex technique). An affinity-purified polyclonal rabbit antiserum to human bFGF was used as a primary antibody. The eluate of malignant thyroid tumor tissues from the heparin-Sepharose column was examined by Western blot analysis to elucidate the molecular weight form. With immunohistochemical staining, bFGF was frequently detected in the cytoplasm of malignant thyroid tumors compared to tissues of the benign diseases and normal controls. With anaplastic carcinoma, immunoreactivity of the tumor cells was particularly strong. In the correlative analyses between UICC TNM classification and bFGF staining in papillary carcinoma, there were significant differences when relating positive staining to the grade of nodal metastases. By Western blot analysis, the bFGF immunoreactivity was specifically detected in the two forms, with molecular weights of 18 and 33 kDa. The high-molecular-weight form was detected in only anaplastic carcinoma. The present investigations demonstrated a close correlation between the expression of bFGF and the degree of malignancy. bFGF might play an important role in promoting lymph node metastases. Moreover, the high-molecular-weight form of bFGF might have an intense influence on tumor growth.

Résumé

Une étude morphologique et biologique a été effectuée pour clarifier la signification du facteur de croissance des fibroblastes de base (bFGF) dans les tumeurs de la thyroïde chez l'homme. On a étudié 71 tumeurs de la thyroïde (50 cancers papillaires, 14 cancers folliculaires, 6 adénomes solitaires, et 7 cancers anaplasiques, 11 adénomes folliculaires, 6 goitres adénomateux et 6 Maladies de Basedow) en utilisant des méthodes immunohistochimiques et notamment la technique du complexe avidinebiotine-peroxydase. On a employé un anticorps primaire fabriqué à partir d'un antisérum polyclonal de lapin purifié dirigé contre le bFGF humain. L'éluat des tissus thyroïdiens malins provenant de la colonne héparine-sepharose a été examiné selon la technique Western Blot pour déterminer son poids moléculaire. Le bFGF a été détecté plus fréquemment dans le cytoplasme des tumeurs thyroïdiennes malignes que dans les maladies bénignes et les contrôles. Dans le cancer anaplasique, l'immunoréactivité des cellules cancéreuses a été particulièrement forte. En ce qui concerne la corrélation entre la classification TNM de l'Union Internationale contre le Cancer et la coloration bFGF des cancers papillaires, il y avait des différences significatives correspondant au degré d'envahissement des ganglions lymphatiques. Dans l'analyse selon la technique du Western blot, l'immunoréactivité bFGF a été détectée spécifiquement sous les deux formes de bFGF ayant des poids moléculaires de 18 et de 33 K, respectivement. Le poids moléculaire de 33K n'a été détecté que dans le cancer anaplasique. Cette étude démontre la corrélation étroite entre l'expression bFGF et le degré de malignité. Le bFGF peut probablement jouer un rôle important dans la survenue de métastase lymphatique. Le type à poids moléculaire élevé de bFGF pourrait influencer d'advantage la croissance tumorale.

Resumen

Se emprendió un estudio morfológico y biológico, con el propósito de clarificar la significación biológica del factor básico de crecimiento de fibroblastos (FBCF) en los neoplasmas de la glándula tiroides humana.

Setenta y un tumores malignos (50 carcinomas papilares, 14 carcinomas foliculares y 7 carcinomas anaplásico), 11 adenomas foliculares, 6 bocios adenomatosos y 6 tejidos de glándula con enfermedad de Graves fueron examinados mediante métodos inmunohistoquímicos (técnica del complejo avidina-biotinaperoxidasa); se utilizó un antisuero policlonal purificado contra el FBCF humano, como anticuerpo primario. Además, se utilizó el análisis de Western blot para elucidar la forma de peso molecular.

Con la coloración inmunohistoquímica, el FBCF fue detectado con frecuencia en el citoplasma de los tumores malignos de la tiroides, en comparación con lo observado en la enfermedad benigna y en los controles normales. La inmunorreactividad tumoral fue particulamente fuerte en el carcinoma anaplásico. En el análisis correlativo entre la clasificiación TNM UICC y la coloración del FBCF en el carcinoma papilar, se hallaron diferencias significativas relativas a la coloración positiva y al grado de la metástasis ganglionares.

En el análisis Western blot, la inmunorreactividad FBCF fue específicamente detectada en las dos formas diferentes con pesos moleculares de 18 K y 33 K. La forma de alto peso molecular fue detectada sólamante en el carcinoma anaplásico.

La presente investigación demuestra una estrecha correlación entre la expresión de FBCF y el grado de malignidad. El FBCF puede jugar un papel importante en promover las metástasis ganglionares. Además, la forma de alto peso molecular del FBCF puede tener una influencia más intensa sobre el crecimiento del tumor.

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Authors and Affiliations

  1. Department of Surgery, Shinshu University School of Medicine, 390, Matsumoto, Japan

    Kiyoshi Shingu M.D. & Akira Sugenoya M.D.

  2. Department of Pathology, Shinshu University School of Medicine, 390, Matsumoto, Japan

    Nobuo Itoh M.D.

  3. School of Allied Medical Science, Shinshu University, 390, Matsumoto, Japan

    Ryoji Kato M.D.

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  1. Kiyoshi Shingu M.D.
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  2. Akira Sugenoya M.D.
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  3. Nobuo Itoh M.D.
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  4. Ryoji Kato M.D.
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Shingu, K., Sugenoya, A., Itoh, N. et al. Expression of basic fibroblast growth factor in thyroid disorders. World J. Surg. 18, 500–505 (1994). https://doi.org/10.1007/BF00353747

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