Influence of hMLH1 methylation, mismatch repair deficiency and microsatellite instability on chemoresistance of testicular germ-cell tumors

Judit Olasz, László Mándoky, Lajos Géczi, István Bodrogi, Orsolya Csuka, Mihály Bak

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Cisplatin-based chemotherapy can cure more than 80% of metastatic germ-cell testicular tumors (GCTs). The response to cisplatin-based chemotherapy has been related to Microsatellite Instability (MSI), which is caused by genetic or epigenetic changes in genes of the DNA Mismatch Repair (MMR) pathway. Patients and Methods: We investigated 15 refractory and 36 chemosensitive GCTs for immunohistochemical loss of hMLH1, hMSH2 and hMSH6 protein expressions, in conjunction with hMLH1 gene methylation and MSI of GCTs, with a complete follow-up. Results: A loss of either of the MMR protein expressions was detected in 14 cases (27.5%). Pathological hMLH1 protein expression was seen in 10 cases (19.6%). hMLH1 methylation was found in 11 cases (21.6%) and was highly correlated with loss of hMLH1 expression (p<0.0001) and with immunohistochemically-detected MMR deficiency (p=0.0005). MSI was found in 16 cases (31.4%). There was no correlation between hMLHl methylation and MSI. Neither hMLH1 methylation status, nor MSI correlated with any of the clinicopathological parameters investigated (tumor stage, histology, resistance to systemic treatment). Conclusion: hMLH1 gene methylation was detected as a common alteration in GCTs, and correlated with the loss of hMLH1 protein expression (p<0.0001). Neither hMLH1 gene methylation, MMR deficiency, nor MSI showed a relationship with the relevant clinicopathological parameters.

Original languageEnglish
Pages (from-to)4319-4324
Number of pages6
JournalAnticancer research
Volume25
Issue number6 B
Publication statusPublished - Nov 1 2005

Keywords

  • Chemoresistance
  • MMR
  • MSI
  • Testicular germ-cell tumor
  • hMLH1 methylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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