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Comparison of deoxyribonucleic acid ploidy and nuclear expressed p62 c-myc oncogene in the prognosis of colorectal cancer

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Abstract

A simultaneous flow cytometric assay of the nuclear expressed protein product of the c-myc oncogene p62 and deoxyribonucleic acid (DNA) ploidy in archival paraffin-embedded tumor material was undertaken in 179 patients with colorectal cancer, followed for up to 9 years. DNA ploidy showed a survival advantage for diploid tumors (χ 21 =5.39,p= 0.020) and could be used to further divide patients with Dukes' A tumors (χ 21 =4.87,p=0.027) and Dukes' C tumors (χ 21 =5.33,p=0.021). By dividing patients into 2 levels of tumor expression of p62 c-myc, there was a trend for improved survival in patients with low expression (χ 21 =3.65,p=0.056). A combination of ploidy status and p62 c-myc expression improved upon survival prediction by ploidy alone in providing 3 groups (χ 22 =7.86,p=0.0197). While these results do not suggest a replacement for the Dukes' staging for prognosis (χ 23 =33.82,p<0.00001), they strongly support the concept that enhanced expression of c-myc oncogene is associated with the progression of colorectal cancer.

Résumé

Par la cytométrie de flux, on a étudié simultanément le produit de l'oncogène c-myc p62, et la ploïdie de l'acide désoxyribonucléique (ADN) dans du matériel tumoral inclus dans la paraffine chez 179 patients ayant un cancer colorectal, répertoriés rétrospectivement et suivis pour un maximum de 9 ans. L'étude de la ploïdie ADN a montré un avantage de survie lorsque la tumeur était diploïde (χ 21 =5.39,p=0.020). Ces résultats pouvaient être utilisés pour classer les patients ayant une tumeur du stade A de Dukes (χ 21 =4.87,p=0.027) de ceux ayant une tumeur du stade C de Dukes (χ 21 =5.33,p=0.021). En classant les patients selon leur niveau d'expression tumorale de l'oncogène p62 c-myc, on a constaté une tendance de meilleure survie chez les patients ayant une expression faible (χ 21 =3.65,p=0.056). L'association de l'étude de la ploïdie et de l'expression de p62 c-myc améliore la prédiction de survie par rapport à l'étude de la ploïdie seule. Trois groupes sont ainsi définis (χ 22 =7.86,p=0.0197). Alors que ces résultats ne suggèrent pas de remplacer la classification de Dukes pour le pronostic (χ 23 =33.82,p<0.00001), il semble que l'expression augmentée de l'oncogène c-myc est fortement associée avec l'évolutivité du cancer colorectal.

Resumen

Se realizó la determinación de la expresión nuclear del producto proteico del oncogen p62 c-myc y la ploidia de ácido deoxirri-bonucleico (DNA) por análisis de citometría de flujo en material tumoral procesado en parafina en 179 pacientes con cáncer colorrectal que fueron seguidos hasta por 9 años. El estudio de la ploidia de DNA demostró una mayor supervivencia para los tumores diploides (χ 21 =5.39,p=0.020) y permitió subdividir los pacientes entre aquellos con tumores Dukes A (χ 21 =4.87,p =0.027) y Dukes C (χ 21 =5.33,p=0.021). Al dividir los pacientes en 2 niveles de expresión tumoral de p62 c-myc, se halló una tendencia hacia una mayor supervivencia en los pacientes con bajos niveles de expresión (χ 21 =3.65,p=0.056). La combinación del estado de la ploidia y de la expresión de p62 c-myc incrementó la capacidad de predecir supervivencia sobre el uso de la ploidia solamente al definir 3 grupos (χ 22 =7.86,p= 0.0197). Aunque estos resultados no permiten recomendar que se reemplace el método de Dukes en la estadificación del tumor para definir pronóstico (χ 23 =33.82,p<0.00001) sí proveen un fuerte soporte al concepto de que una incrementada expresión del oncogen c-myc está asociado con progresión del cáncer colorrectal.

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Authors and Affiliations

  1. University Department of Surgery, Dudley Road Hospital, B18 7QH, Birmingham, England, Uk

    S. Rowley F.R.C.S., K. M. Newbold M.R.C.Path., J. Gearty M.R.C.Path., M. R. B. Keighley M.S., F.R.C.S., I. A. Donovan M.D., F.R.C.S. &  J. P. Neoptolemos M.A., M.D., F.R.C.S.

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  1. S. Rowley F.R.C.S.
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  2. K. M. Newbold M.R.C.Path.
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  3. J. Gearty M.R.C.Path.
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  4. M. R. B. Keighley M.S., F.R.C.S.
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  5. I. A. Donovan M.D., F.R.C.S.
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Rowley, S., Newbold, K.M., Gearty, J. et al. Comparison of deoxyribonucleic acid ploidy and nuclear expressed p62 c-myc oncogene in the prognosis of colorectal cancer. World J. Surg. 14, 545–550 (1990). https://doi.org/10.1007/BF01658688

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