title: Immunohistochemical molecular gene expression profile of metastatic brain tumor as a potent personalized medicine.
abstract: Recent progress in molecule-targeting therapy may yield personalized therapeutic strategies for patients with metastatic brain tumors (MBT), the most frequently encountered intracranial tumors. For this purpose, we investigated the molecular expression profile of MBT to establish the pathological basis for personalized diagnosis. We studied 166 MBT specimens including 70 cases of lung cancer and 34 cases of breast cancer, and performed immunostaining for EGFR, COX-2, and O-6-methylguanine-DNA methyltransferase (MGMT), among others, which could be target molecules for therapeutic agents or enable prediction of drug efficacy. Loss of MGMT expression was observed in approximately 20-40% of MBT derived from lung, breast, and gastrointestinal cancers, indicating the possibility of treatment of MBT patients with temozolomide. In addition, MBT expressed a variety of receptor tyrosine kinases, for example EGFR and HER2, and signal transduction molecules, for example phospho-mTOR and COX-2, irrespective of tumor origin, enabling individualized medication with molecule-targeting drugs. We also identified alteration of molecular expression profile in 4 MBT cases during recurrence. Our results not only reveal the molecular characteristics of MBT but also suggest the possibility of potent personalized medicine for MBT patients.
authors.affiliation: Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishihara
authors.forename: Sayaka
authors.initials: S
authors.lastname: Yuzawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mohri
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kanno
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hatanaka
authors.forename: Taichi
authors.initials: T
authors.lastname: Kimura
authors.forename: Mishie
authors.initials: M
authors.lastname: Tanino
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D015254:DNA Modification Methylases / Q000032:analysis*; D045643:DNA Repair Enzymes / Q000032:analysis*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D057285:Precision Medicine; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000032:analysis*
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D003606:Dacarbazine; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins; C515491:MGMT protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human