O6-Methylguanine-DNA methyltransferase expression and prognostic value in brain metastases of lung cancers

Pei Fang Wu, Kuan Ting Kuo, Lu Ting Kuo, Yi Ting Lin, Wei Chung Lee, Yen Shen Lu, Chih Hsin Yang, Ruey Meei Wu, Yong Kwang Tu, Jui Chang Tasi, Ham Min Tseng, Sheng Hong Tseng, Ann Lii Cheng, Ching Hung Lin

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

O6-Methylguanine-DNA methyltransferase (MGMT) is critical for repairing pro-mutagenic DNA bases and is correlated with response to alkylating agents in cancers. Since there is great interest in pursuing the potential role of temozolomide, a novel alkylating agent, in the treatment of brain metastases, this study aimed to evaluate MGMT expression as well as its prognostic value in this devastating disease. We studied the expression and methylation status of MGMT in 86 brain metastases of lung cancers. Twenty of them had matched primary lung tumor tissues available for direct comparison. MGMT expression was assessed by immunohistochemistry (IHC); the methylation status of MGMT promoter was analyzed by nested methylation-specific PCR (MSP) and validated by quantitative real-time PCR analysis. Positive nuclear MGMT expression was detected more frequently in brain metastases as compared with primary lung cancers (83% versus 50%, P=0.004). The discordance in MGMT expression persisted in the 20 paired primary and metastatic tumors (P=0.031). MGMT promoter hypermethylation was highly correlated with loss of MGMT expression. Both univariate and multivariate analyses showed that median overall survival was significantly longer in patients with positive MGMT expression in brain metastases (16.5 versus 3.5 months, P<0.001). In conclusion, MGMT expression was enhanced in brain metastases as compared with the primary lung cancers. MGMT expression in brain metastases was significantly correlated with better survival.

Original languageEnglish
Pages (from-to)484-490
Number of pages7
JournalLung Cancer
Volume68
Issue number3
DOIs
Publication statusPublished - Jun 1 2010
Externally publishedYes

Fingerprint

Methyltransferases
Lung Neoplasms
Neoplasm Metastasis
DNA
Brain
Methylation
Alkylating Agents
temozolomide
O-(6)-methylguanine
Neoplasms
Survival
Real-Time Polymerase Chain Reaction
Multivariate Analysis
Immunohistochemistry

Keywords

  • Brain metastasis
  • Immunohistochemistry
  • MGMT
  • O-Methylguanine-DNA methyltransferase

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Wu, P. F., Kuo, K. T., Kuo, L. T., Lin, Y. T., Lee, W. C., Lu, Y. S., ... Lin, C. H. (2010). O6-Methylguanine-DNA methyltransferase expression and prognostic value in brain metastases of lung cancers. Lung Cancer, 68(3), 484-490. https://doi.org/10.1016/j.lungcan.2009.08.010

O6-Methylguanine-DNA methyltransferase expression and prognostic value in brain metastases of lung cancers. / Wu, Pei Fang; Kuo, Kuan Ting; Kuo, Lu Ting; Lin, Yi Ting; Lee, Wei Chung; Lu, Yen Shen; Yang, Chih Hsin; Wu, Ruey Meei; Tu, Yong Kwang; Tasi, Jui Chang; Tseng, Ham Min; Tseng, Sheng Hong; Cheng, Ann Lii; Lin, Ching Hung.

In: Lung Cancer, Vol. 68, No. 3, 01.06.2010, p. 484-490.

Research output: Contribution to journalArticle

Wu, PF, Kuo, KT, Kuo, LT, Lin, YT, Lee, WC, Lu, YS, Yang, CH, Wu, RM, Tu, YK, Tasi, JC, Tseng, HM, Tseng, SH, Cheng, AL & Lin, CH 2010, 'O6-Methylguanine-DNA methyltransferase expression and prognostic value in brain metastases of lung cancers', Lung Cancer, vol. 68, no. 3, pp. 484-490. https://doi.org/10.1016/j.lungcan.2009.08.010
Wu, Pei Fang ; Kuo, Kuan Ting ; Kuo, Lu Ting ; Lin, Yi Ting ; Lee, Wei Chung ; Lu, Yen Shen ; Yang, Chih Hsin ; Wu, Ruey Meei ; Tu, Yong Kwang ; Tasi, Jui Chang ; Tseng, Ham Min ; Tseng, Sheng Hong ; Cheng, Ann Lii ; Lin, Ching Hung. / O6-Methylguanine-DNA methyltransferase expression and prognostic value in brain metastases of lung cancers. In: Lung Cancer. 2010 ; Vol. 68, No. 3. pp. 484-490.
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AU - Tasi, Jui Chang

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AU - Tseng, Sheng Hong

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