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The Histochemical Journal

, Volume 33, Issue 8, pp 459–467 | Cite as

DNA Mismatch Repair Enzyme hMSH2 in Malignant Melanoma: Increased Immunoreactivity as Compared to Acquired Melanocytic Nevi and Strong MRNA Expression in Melanoma Cell Lines

  • Knuth Rass
  • Paul Gutwein
  • Cornelius Welter
  • Viktor Meineke
  • Wolfgang Tilgen
  • Jörg Reichrath
Article

Abstract

Mutations in the mismatch DNA repair gene human MutS homologen 2 (hMSH2) are causative for microsatellite instability and carcinogenesis in various human tumours, including hereditary nonpolyposis colorectal cancer. Because microsatellite instability has been detected in malignant melanoma, we have investigated hMSH2 in melanocytic tumours. We found strong nuclear immunoreactivity for hMSH2 that was elevated in malignant melanoma and melanoma metastases as compared to acquired nevi. These findings suggest that increased genomic instability in malignant melanoma is associated with elevated protein levels of this DNA repair enzyme. hMSH2 is not exclusively regulated by proliferative activity in melanocytes, because there was no correlation between staining patterns of hMSH2 and the proliferation marker Ki-67. In contrast, immunoreactivity scores for hMSH2 and p53 were both upregulated in malignant melanocytic tumours. These findings support the concept that hMSH2 gene expression may be regulated in melanocytes by the p53 protein, as has been reported previously in other tissues. Using the reverse transcription-polymerase chain reaction, we detected strong hMSH2 mRNA expression in each of 8 melanoma cell lines analysed (highest amounts in SK-MEL-25 cells, lowest amounts in MML-I cells). In conclusion, our findings indicate that hMSH-2 may be of importance for genetic stability, tumorigenesis and progression of malignant melanoma.

Keywords

Melanoma Melanoma Cell Line Microsatellite Instability Hereditary Nonpolyposis Colorectal Cancer Melanocytic Nevus 
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.

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Knuth Rass
    • 1
  • Paul Gutwein
    • 1
    • 2
  • Cornelius Welter
    • 2
  • Viktor Meineke
    • 3
  • Wolfgang Tilgen
    • 1
  • Jörg Reichrath
    • 4
  1. 1.Department of DermatologyThe Saarland University HospitalHomburg/SaarGermany
  2. 2.Department of Human GeneticsThe Saarland University HospitalHomburg/SaarGermany
  3. 3.Institute of RadiobiologySanitätsakademie der BundeswehrMunichGermany
  4. 4.Department of DermatologyThe Saarland University HospitalHomburg/SaarGermany

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