title: Expression of O⁶-methylguanine DNA methyltransferase (MGMT) and immunohistochemical analysis of 12 pineal parenchymal tumors.
abstract: Pineal parenchymal tumors (PPTs) are rare neoplasms which occupy less than 1% of primary CNS tumors. Because of their rare incidence, previous reports on PPTs are limited in number and the useful molecular markers for deciding histological grading and even selecting chemotherapy are undetermined. In this study, we conducted immunohistochemical analysis of 12 PPT specimens, especially for expression of O⁶-methylguanine DNA methyltransferase (MGMT) to assess whether temozolomide (TMZ) could serve as a possible alternative therapy for PPTs. We analyzed 12 PPTs, consisting of three pineocytomas, six PPTs of intermediate differentiation (PPTIDs), and three pineoblastomas. Immunohistochemical analysis was performed using antibodies against MGMT, synaptophysin, neurofilament protein (NF), p53, and neuronal nuclear antigen (NeuN). Immunohistochemically, 11 out of 12 cases were positive for MGMT. The mean MIB-1 labeling index was less than 1% in pineocytoma, 3.5% in PPTID, and 10.5% in pineoblastoma. All 12 cases were positive for synaptophysin and 11 cases, except one PPTID case, showed positive for NF. Nuclear staining of NeuN was negative in all cases although cytoplasmic staining of NeuN was observed in five cases. No case was positive for p53. Eleven out of 12 cases of PPTs demonstrated MGMT expression, suggesting chemoresistancy to TMZ treatment. This is the first report showing MGMT expression in PPTs. In addition, MIB-1 labeling index correlated with WHO grade, although the immunoreactivity of synaptophysin, NF, NeuN and p53 did not correlate with the histological grade.
authors.affiliation: Laboratory of Cancer Research, Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kanno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishihara
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Oikawa
authors.forename: Yoshimaru
authors.initials: Y
authors.lastname: Ozaki
authors.forename: Junichi
authors.initials: J
authors.lastname: Murata
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sawamura
authors.forename: Masahito
authors.initials: M
authors.lastname: Kato
authors.forename: Kanako
authors.initials: K
authors.lastname: Kubota
authors.forename: Mishie
authors.initials: M
authors.lastname: Tanino
authors.forename: Taichi
authors.initials: T
authors.lastname: Kimura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagashima
authors.forename: Tamio
authors.initials: T
authors.lastname: Itoh
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000378:metabolism; D010870:Pineal Gland / Q000378:metabolism*; D010871:Pinealoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016708:Synaptophysin / Q000378:metabolism; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019394:Ki-67 Antigen; D016900:Neurofilament Proteins; D016708:Synaptophysin; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide