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Expression of a potential metastasis suppressor gene (nm23) in thyroid neoplasms

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Abstract

Identification of multiple clinical and pathologic prognostic factors in differentiated thyroid cancer has permitted some degree of risk stratification. However, these clinical indices fail to distinguish potential intrinsic differences in tumor virulence. The nm23 gene has been identified as a potential metastasis suppressor gene that is homologous to nucleoside diphosphate kinases. Studies in human breast cancer have shown a significant inverse correlation between nm23 levels and nodal involvement/tumor recurrence. Given the possible clinical utility of a marker of metastatic potential in the management of thyroid carcinoma, we examined 34 thyroid neoplasms and a human medullary thyroid cancer (MTC) cell line (TT) for nm23 expression. Normalized nm23 expression was assessed by Northern analysis of tumor RNA. nm23 Expression (tumor expression/TT cell expression, mean ±SE) was 1.14 ±0.15* in MTCs (n =5), 0.70 ±0.10* in follicular cancers (n=6), 0.51 ±0.11 in papillary cancers (n=19), and 0.31 ±0.03 in follicular adenomas (n=4) (*p< 0.05 when compared to adenomas). Within histologicgroups, we found no correlation between nm23 expression and nodal involvement or distant métastases. Our results indicate that thyroid neoplasms of different histologies express varying levels of the nm23 transcript. Although nm23 expression seems diminished in metastatic breast cancer, it appears not to be the case in metastatic thyroid cancer. The nm23 gene may therefore have different roles in the evolution and metastases of different neoplasms.

Résumé

L'identification de facteurs pronostiques clinique et histologique dans le cancer thyroïde permettrait de stratifier les patients selon le risque encouru. Cependant, les indices cliniques ne sont pas toujours fiables en ce qui concerne le potentiel tumoral. Le gène nm23 a été identifié comme un gène de répression de métastase, homologue aux kinases des nucléides diphosphorées. Des études récentes chez la femme ayant un cancer du sein ont démontré un rapport inverse entre les taux de gène nm23 et la présence de métastase ou de récidive ganglionnaire. Etant donnée la valeur potentielle d'un tel marqueur de métastase, nous avons étudié la lignée cellulaire (LC) de 35 patients ayant un cancer de la thyroïde (dont un cancer médullaire (MTC)) pour la présence de nm23. L'expression nm23 a été évaluée par l'analyse Northern du contenu tumoral en ARN. Le rapport expression tumoral/LC (moyen ±ET) a été de 1.14±0.15* dans le MTC, de 0.70±0.10* dans le cancer folliculaire (n=6), de 0.51 ±0.11 dans le cancer papillaire (n= 19) et de 0.31±0.03 dans l'adénome folliculaire (n=4) (*=p <0.05 comparé aux adénomes). A l'intérieur des différents groupes histologiques, aucune corrélation significative n'a été retrouvée entre l'expression nm23 et l'envahissement ganglionnaire ou les métastases à distance. Nos résultats indiquent que les cancers de la thyroïde ont des taux différents de nm23. Alors que l'expression nm23 paraît être diminuée dans le cancer du sein métastatique, cela peut n'être pas vrai pour le cancer de la thyroïde métastatique. La gène nm23 peut donc avoir un rôle différent dans l'évolution et le développement des métastases de cancers différents.*=p<0.05

Resumen

Los pacientes con cancer diferenciado de la glándula tiroides (papilar, folicular, medular) generalmente tienen buen pronóstico a largo plazo. Sin embargo, existen subgrupos de pacientes con un tipo agresivo de neoplasma, quienes desarrollan metástasis sistémicas y eventualmente mueren por causa de su enfermedad.

La identificación de una multitud de factores de pronóstico, clínicos y anatomopatológicos, en el cáncer diferenciado de la tiroides permite un cierto grado de estratificación, aunque tales indicadores no son capaces de diferenciar potenciales variaciones intrînsecas en la virulencia del tumor.

El gen nm 23 ha sido identificado como uno potencialmente supresor de metastasis, el cual es homólogo con las nucléosido difosfato quinasas. Estudios recientes en cancer mamario humano han demostrado una correlación inversa entre los nivelés de nm 23 y la invasión ganglionar/recurrencia tumoral. Considerando la posible utilidad clínica de disponer de un marcador del potencial metastásico en el manejo del carcinoma tiroideo, nos propusimos examinar 34 neoplasmas tiroideos y una línea celular (TT) de cáncer medular de tiroides en cuanto a expresión de nm 23, según el “Northern analysis” del RNA tumoral. La expresión normalizada de nm 23 (expresión tumoral/expresión de células TT, media ±SE) fue 1.14 ±0.15* en los cánceres medulares (n=5), 0.70 ±0.10* en cánceres foliculares (n=6), 0.51 ±0.11 en cánceres papilares (n=19) y 0.31 ±0.03 en adenomas foliculares (n=4) (*=p<0.05 al comparar con adenomas). No se halló correlación entre la expresión de nm 23 y la invasión ganglionar o metástasis distantes dentro de los grupos histológicos. Nuestros resultados indican que los neoplasmas tiroideos de diferentes histologías expresan nivelés variables de la transcription de nm 23. Sin embargo, aunque la expresión de nm 23 parece estar disminuida en el cáncer mamario metastásico, ésto no parece ocurrir en el cancer tiroideo metastásico. Por consiguiente, el gen nm 23 puede jugar diferentes papeles en la evolution y en las metástasis de los diferentes neoplasmas.

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Correspondence to Sundeep Khosla M.D..

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Farley, D.R., Eberhardt, N.L., Grant, C.S. et al. Expression of a potential metastasis suppressor gene (nm23) in thyroid neoplasms. World J. Surg. 17, 615–620 (1993). https://doi.org/10.1007/BF01659123

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Keywords

  • Adenoma
  • Thyroid Carcinoma
  • Thyroid Neoplasm
  • Differentiate Thyroid Cancer
  • Medullary Thyroid Cancer