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World Journal of Surgery

, Volume 26, Issue 6, pp 726–731 | Cite as

Metallothionein: Early marker in the carcinogenesis of ulcerative colitis-associated colorectal carcinoma

  • Matthias BruewerEmail author
  • Kurt W. Schmid
  • Christian F. Krieglstein
  • Norbert Senninger
  • Guido Schuermann
Original Scientific Reports

Abstract

Metallothioneins (MTs) are zinc-binding proteins whose over-expression may lead to sequestration of zinc ions and consequently to functional inactivation of the p53 tumor suppressor gene. The aim of the study was to investigate the potential role of MTs in the carcinogenesis of ulcerative colitis (UC) as well as possible effects on p53 function. The monoclonal antibodies E9 (anti-MT), DO-7, and 1801 (anti-p53) and the polyclonal antibody CM-1 (anti-p53) were used to stain formalin-fixed, paraffin-embedded colon specimens obtained from 14 patients with UC-associated colorectal carcinoma (CAC), 13 with high-grade dysplasia (HGD), 10 with low-grade dysplasia (LGD), and 30 with UC without dysplasia or carcinoma. Statistical significance (p<0.05) was assessed using Fisher’s exact test. Positive MT staining (>20% of tumor, dysplastic, or epithelial cells) was found in most UC and LGD but in only a small percentage of HGD and CAC (p<0.01 for CAC vs. UC and LGD vs. HGD). Positive p53 immunoreactivity was observed predominantly in HGD and CAC but not in LGD and UC (p<0.01 for CAC vs. UC and HGD vs. LGD). In histologically normal tissue neighboring CAC, significant MT expression was found in six of seven specimens with simultaneous lack of p53 expression. MT overexpression may represent an important early step in the development of CAC independent of p53 expression and should be investigated in the long term as an independent cancer risk factor in UC.

Keywords

Ulcerative Colitis Cysteinyl Residue Colectomy Specimen Sporadic Colorectal Carcinoma Ulcerative Colitis Tissue 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Résumé

Les métallothionéines (MT) sont des protéines liées au zinc dont la surexpression peut provoquer une séquestration des ions zinc et par conséquent une inactivation fonctionnelle du gène de suppression tumorale p53. Le but de cette étude a été d’examiner le rôle potentiel des MT dans la carcinogenèse au cours de la recto-colite hémorragique (RCH), de même que les effets sur la fonction p53. Les anticorps monoclonaux E9 (anti-MT), DO-7 et 1801 (anti-p53) ainsi que l’anticorps polyclonal CM-1 (anti-p53) ont été utilisés pour colorer les pièces de côlon, fixées par le formol et en paraffine, obtenues à partir de 14 patients atteints de RCH et de cancer colorectal (CCR), 13 patients porteurs de dysplasie de haut grade (DHG), 10 patients porteurs de dysplasie de bas grade (DBG) et 30 patients ayant une RCH sans dysplasie ni cancer. La signification statistique recherchée par l’utilisation du test exact de Fisher a été fixée à 0.05. Une coloration MT positive (définie comme >20% des cellules tumorales, dysplasiques ou épithéliales) a été retrouvée dans la majorité des cas de RCH et de DBG, mais seulement dans une minorité de patients porteurs de DHG et/ou CCR (p<0.01 pour CRC vs RCH et DBG vs DHG). L’immunoréactivité du P53 était positive essentiellement pour les patients DHG et CCR, mais pas pour les DBG ou RCH (p<0.01 pour CRC vs RCH et pour DHG vs DBG). Dans le tissu histologiquement normal aux alentours du CCR, on a retrouvé une expression MT significative mais sans expression de P53 dans six des sept pièces. La surexpression MT pourrait représenter une étape précoce importante dans le développement du CCR, indépendamment de l’expression p53 et devrait être recherchée comme un facteur de risque indépendant de cancer au cours d’une RCH, dans le suivi au long cours.

Resumen

Las melatoninas (MT) son proteínas ligadoras de zinc cuyas superexpresión puede Ilevar al secuestro de los iones de zinc y, en consecuencia, a la inactivación del gen p53 de supresión tumoral. El propósito del presente estudio fue investigar el papel de las MT en la carcinogénesis de la colitis ulcerativa (CU), así como a los posibles efectos sobre la función del p53. Se utilizaron los anticuerpos monoclonales E9 (anti-MT), DO-7 y 1801 (anti-p53) y el anticuerpo policional CM-1 (anti-p53) para teñir especímenes colónicos incluidos en parafina obtenidos de 14 pacientes con carcinoma colorectal asociado a CU (CCA), de 13 pacientes con displasia de alto grado (DAG), de 10 pacientes con displasia de bajo grado (DBG) y de 30 pacientes con CU sin displasia ni carcinoma. La significancia estadística (p<0.05) se determinó por la prueba exacta de Fisher. Se registró tinción positiva para MT (>20% de las células tumorales, displásicas o epiteliales) en la mayoría de las CU y DBG, pero sólo en la minoría de la DAG y CCA (p<0.01 entre CCA vs CU y DBG vs DAG). Se encontró expresión significante de MT en el tejido histológicamente normal vecino del CCA en 6 de 7 especímenes con ausencia de expresión de p53. La superexpresión de MT puede representar una fase temprana en el desarrollo del CCA, independiente de la expresión de p53 y debe ser investigada en el seguimiento a largo plazo como un factor de riesgo independiente en la CU.

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Copyright information

© Société Internationale de Chirurgie 2002

Authors and Affiliations

  • Matthias Bruewer
    • 1
    Email author
  • Kurt W. Schmid
    • 2
  • Christian F. Krieglstein
    • 1
  • Norbert Senninger
    • 1
  • Guido Schuermann
    • 1
  1. 1.Department of General SurgeryUniversity of MuensterMuensterGermany
  2. 2.Institute of PathologyUniversity of EssenEssenGermany

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