Expression profiling of O6 methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases

BMC Cancer

Research Article

Hai-Jun Wang¹  Dong-Sheng He¹  Zhi-Gang Mao¹  Bin Hu¹  Xiao-Bing Jiang²  Yong-Hong Zhu³  Xin Wang³  Bing-Bing Song³ 

[1] Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Haizhu, Yixian Rd, Guangzhou, Guangdong, China;Key Laboratory of Pituitary Adenoma in Guangdong Province, 510080, Guangzhou, China;Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Haizhu, Yixian Rd, Guangzhou, Guangdong, China;Key Laboratory of Pituitary Adenoma in Guangdong Province, 510080, Guangzhou, China;Department of Neurosurgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 510060, Guangzhou, China;Key Laboratory of Pituitary Adenoma in Guangdong Province, 510080, Guangzhou, China;Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, China;

关键词: Pituitary Adenoma;    Promoter Methylation;    Cabergoline;    Prolactinomas;    MGMT Promoter Methylation;   

DOI  :  10.1186/s12885-015-1595-0

 received in 2015-03-05, accepted in 2015-08-07,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundLow-level expression of O6 methylguanine-DNA-methyl transferase (MGMT) prolactinomas has been noted previously in case reports, although what modulates MGMT expression remains unclear. This study therefore aimed to delineate the factors regulating MGMT expression in prolactinomas.MethodsWe retrospectively reviewed 136 prolactinoma patients who were treated in our center between January 2000 and September 2013. Expression of MGMT, Ki-67, and p53 protein were examined by immunohistochemical staining, and MGMT promoter methylation evaluated with methylation-specific PCR.ResultsMGMT immunopositivity was <25 % in 106/136 tumor specimens (77.94 %). MGMT immunoexpression was positively correlated with age (r = 0.251, p = 0.003), but inversely correlated with p53 staining (r = −0.153, p = 0.021). Moreover, reduced MGMT expression was more frequent in atypical prolactinomas (p = 0.044). Methylated MGMT promoter was confirmed in 10/46 specimens (21.7 %), all of which had low level or absent MGMT staining. Both p53 protein (r = −0.33, p = 0.025) and promoter methylation (r = −0.331, p = 0.025) were negatively associated with MGMT expression. Multivariate logistic analysis indicated that age (odds ratio [OR] = 1.127. 95 % confidence interval [CI] 1.027–1.236, p = 0.012) and p53 (OR = 0.116. 95 % CI 0.018–0.761, p = 0.025) staining were independent determents of MGMT expression.ConclusionsThe majority of prolactinomas, especially atypical prolactinomas, showed low-level or no MGMT immunoexpression, providing a rationale for the utility of temozolomide as an alternative to managing prolactinomas. In summary, epigenetic and transcriptional regulation are involved in silencing MGMT expression.

【 授权许可】

CC BY   
© Jiang et al. 2015