title: Expression profiling of O(6) methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases.
abstract: BACKGROUND
  Low-level expression of O(6) 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.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  MGMT 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Haizhu, Yixian Rd, Guangdong, Guangzhou, China. su35qq@hotmail.com.|Key Laboratory of Pituitary Adenoma in Guangdong Province, Guangzhou, 510080, China. su35qq@hotmail.com.|Department of Neurosurgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China. su35qq@hotmail.com.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Haizhu, Yixian Rd, Guangdong, Guangzhou, China. warm0809@qq.com.|Key Laboratory of Pituitary Adenoma in Guangdong Province, Guangzhou, 510080, China. warm0809@qq.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Haizhu, Yixian Rd, Guangdong, Guangzhou, China. hedsh@21cn.com.|Key Laboratory of Pituitary Adenoma in Guangdong Province, Guangzhou, 510080, China. hedsh@21cn.com.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: He
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Haizhu, Yixian Rd, Guangdong, Guangzhou, China. mmh222111@yaoo.com.cn.|Key Laboratory of Pituitary Adenoma in Guangdong Province, Guangzhou, 510080, China. mmh222111@yaoo.com.cn.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Mao
authors.affiliation: Key Laboratory of Pituitary Adenoma in Guangdong Province, Guangzhou, 510080, China. 383316428@qq.com.|Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. 383316428@qq.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Pituitary Adenoma in Guangdong Province, Guangzhou, 510080, China. 1099094540@qq.com.|Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. 1099094540@qq.com.
authors.forename: Bing-Bing
authors.initials: BB
authors.lastname: Song
authors.affiliation: Key Laboratory of Pituitary Adenoma in Guangdong Province, Guangzhou, 510080, China. zhuyongh@mail.sysu.edu.cn.|Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. zhuyongh@mail.sysu.edu.cn.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Haizhu, Yixian Rd, Guangdong, Guangzhou, China. wzwxr_1995@yahoo.com.|Key Laboratory of Pituitary Adenoma in Guangdong Province, Guangzhou, 510080, China. wzwxr_1995@yahoo.com.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015175:Prolactinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53; D019853:O(6)-Methylguanine-DNA Methyltransferase