International Journal of Radiation Oncology * Biology * Physics
Volume 76, Issue 1 , Pages 9-13 , January 2010

Microsatellite Instability Predicts Clinical Outcome in Radiation-Treated Endometrioid Endometrial Cancer

  • Cristina Bilbao, Ph.D.

      Affiliations

    • Canary Institute for Cancer Research, Las Palmas de Gran Canaria, Canary Islands, Spain
    • Department of Radiation Oncology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Canary Islands, Spain
    • Corresponding Author InformationReprint requests to: Cristina Bilbao, Ph.D., Department of Radiation Oncology, Hospital Universitario de Gran Canaria Dr. Negrín, Barranco de la Ballena, s/n. 35010 Las Palmas de Gran Canaria, Spain. Tel: (+34) 619735335; Fax: (+34) 928449127
    • ,
  • Pedro Carlos Lara, M.D., Ph.D.

      Affiliations

    • Canary Institute for Cancer Research, Las Palmas de Gran Canaria, Canary Islands, Spain
    • Department of Radiation Oncology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Canary Islands, Spain
    • ,
  • Raquel Ramírez

      Affiliations

    • Canary Institute for Cancer Research, Las Palmas de Gran Canaria, Canary Islands, Spain
    • Department of Biochemistry and Physiology, Faculty of Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Canary Islands, Spain
    • ,
  • Luis Alberto Henríquez-Hernández, Ph.D.

      Affiliations

    • Canary Institute for Cancer Research, Las Palmas de Gran Canaria, Canary Islands, Spain
    • Department of Radiation Oncology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Canary Islands, Spain
    • ,
  • Germán Rodríguez, Ph.D.

      Affiliations

    • Canary Institute for Cancer Research, Las Palmas de Gran Canaria, Canary Islands, Spain
    • Department of Biochemistry and Physiology, Faculty of Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Canary Islands, Spain
    • ,
  • Orlando Falcón, M.D., Ph.D.

      Affiliations

    • Canary Institute for Cancer Research, Las Palmas de Gran Canaria, Canary Islands, Spain
    • Department of Obstetrics and Gynecology, Hospital Universitario Materno-Infantil de Canarias, Las Palmas de Gran Canaria, Canary Islands, Spain
    • ,
  • Laureano León, Ph.D.

      Affiliations

    • Canary Institute for Cancer Research, Las Palmas de Gran Canaria, Canary Islands, Spain
    • Department of Pathology, Hospital Universitario Materno-Infantil de Canarias, Las Palmas de Gran Canaria, Canary Islands, Spain
    • ,
  • Manuel Perucho, Ph.D.

      Affiliations

    • Burnham Institute for Medical Research, La Jolla, CA
    • ,
  • Bonifacio Nicolás Díaz-Chico, Ph.D.

      Affiliations

    • Canary Institute for Cancer Research, Las Palmas de Gran Canaria, Canary Islands, Spain
    • Department of Biochemistry and Physiology, Faculty of Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Canary Islands, Spain
    • ,
  • Juan Carlos Díaz-Chico, Ph.D.

      Affiliations

    • Canary Institute for Cancer Research, Las Palmas de Gran Canaria, Canary Islands, Spain
    • Department of Biochemistry and Physiology, Faculty of Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Canary Islands, Spain

Received 25 August 2009 ,Revised 18 September 2009 ,Accepted 18 September 2009.

References 

  1. Ionov Y, Peinado MA, Malkhosyan S, et al. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993;363:558–561
  2. Goodfellow PJ. Clinicopathologic significance of DNA mismatch repair defects in endometrial cancer: The devil is in the details. Gynecol Oncol. 2009;113:151–152
  3. Esteller M, Levine R, Baylin SB, et al. MLH1 promoter hypermethylation is associated with the microsatellite instability phenotype in sporadic endometrial carcinomas. Oncogene. 1998;17:2413–2417
  4. Black D, Soslow RA, Levine DA, et al. Clinicopathologic significance of defective DNA mismatch repair in endometrial carcinoma. J Clin Oncol. 2006;24:1745–1753
  5. Zighelboim I, Goodfellow PJ, Gao F, et al. Microsatellite instability and epigenetic inactivation of MLH1 and outcome of patients with endometrial carcinomas of the endometrioid type. J Clin Oncol. 2007;25:2042–2048
  6. Zighelboim I, Schmidt AP, Gao F, et al. ATR mutation in endometrioid endometrial cancer is associated with poor clinical outcomes. J Clin Oncol. 2009;27:3091–3096
  7. Stojic L, Brun R, Jiricny J. Mismatch repair and DNA damage signalling. DNA Repair (Amst). 2004;3:1091–1101
  8. Colombino M, Cossu A, Manca A, et al. Prevalence and prognostic role of microsatellite instability in patients with rectal carcinoma. Ann Oncol. 2002;13:1447–1453
  9. Negri FV, Campanini N, Camisa R, et al. Biological predictive factors in rectal cancer treated with preoperative radiotherapy or radiochemotherapy. Br J Cancer. 2008;98:143–147
  10. Zauber NP, Marotta SP, Berman E, et al. Molecular genetic changes associated with colorectal carcinogenesis are not prognostic for tumor regression following preoperative chemoradiation of rectal carcinoma. Int J Radiat Oncol Biol Phys. 2009;74:472–476
  11. Wong YF, Cheung TH, Lo KW, et al. Detection of microsatellite instability in endometrial cancer: Advantages of a panel of five mononucleotide repeats over the National Cancer Institute panel of markers. Carcinogenesis. 2006;27:951–955
  12. Bellacosa A. Functional interactions and signaling properties of mammalian DNA mismatch repair proteins. Cell Death Differ. 2001;8:1076–1092
  13. Bannister LA, Waldman BC, Waldman AS. Modulation of error-prone double-strand break repair in mammalian chromosomes by DNA mismatch repair protein Mlh1. DNA Repair (Amst). 2004;3:465–474
  14. Wang Q, Ponomareva ON, Lasarev M, et al. High frequency induction of mitotic recombination by ionizing radiation in Mlh1 null mouse cells. Mutat Res. 2006;594:189–198
  15. Siehler SY, Schrauder M, Gerischer U, et al. Human MutL-complexes monitor homologous recombination independently of mismatch repair. DNA Repair (Amst). 2009;8:242–252

 Supported by National Institutes of Health Grant R37 CA63585 (M.P.), the Canary Institute for Cancer Research (ICIC), Fondo de Investigaciones Sanitarias, Fundación Canaria de Investigación y Salud, and Dirección General de Universidades del Gobierno de Canarias (B.N.D.-C., J.C.D.-C.). L.H.-H. and C.B. are recipients of postdoctoral fellowships from the ICIC; R.R. is recipient of a predoctoral fellowship from the Gobierno de Canarias.

 Conflict of interest: none.

PII: S0360-3016(09)03277-5

doi: 10.1016/j.ijrobp.2009.09.035

International Journal of Radiation Oncology * Biology * Physics
Volume 76, Issue 1 , Pages 9-13 , January 2010

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