title: Phenylethanolamine N-methyltransferase downregulation is associated with malignant pheochromocytoma/paraganglioma.
abstract: Malignant pheochromocytoma/paraganglioma (PCC/PGL) is defined by the presence of metastases at non-chromaffin sites, which makes it difficult to prospectively diagnose malignancy. Here, we performed array CGH (aCGH) and paired gene expression profiling of fresh, frozen PCC/PGL samples (n = 12), including three malignant tumors, to identify genes that distinguish benign from malignant tumors. Most PCC/PGL cases showed few copy number aberrations, regardless of malignancy status, but mRNA analysis revealed that 390 genes were differentially expressed in benign and malignant tumors. Expression of the enzyme, phenylethanolamine N-methyltransferase (PNMT), which catalyzes the methylation of norepinephrine to epinephrine, was significantly lower in malignant PCC/PGL as compared to benign samples. In 62 additional samples, we confirmed that PNMT mRNA and protein levels were decreased in malignant PCC/PGL using quantitative real-time polymerase chain reaction and immunohistochemistry. The present study demonstrates that PNMT downregulation correlates with malignancy in PCC/PGL and identifies PNMT as one of the most differentially expressed genes between malignant and benign tumors.
authors.affiliation: Department of Pathology, Konkuk University School of Medicine, Konkuk University Medical Center, Seoul, Korea.
authors.forename: Seung Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Ensel
authors.initials: E
authors.lastname: Oh
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Lee
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Doo-Yi
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Jung
authors.affiliation: The Center for Anti-Cancer Companion Diagnostics, School of Biological Science, Institutes of Entrepreneurial BioConvergence, Seoul National University, Seoul, Korea.
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Junghan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sung Joo
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Gyeongsang National University School of Medicine, Jinju, Korea.
authors.forename: Jung Wook
authors.initials: JW
authors.lastname: Yang
authors.affiliation: Department of Pathology, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Jungsuk
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Young Lyun
authors.initials: YL
authors.lastname: Oh
authors.affiliation: Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea.
authors.forename: Yoon La
authors.initials: YL
authors.lastname: Choi
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000201:enzymology / Q000473:pathology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000473:pathology*; D010235:Paraganglioma / Q000201:enzymology / Q000473:pathology*; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism*; D010673:Pheochromocytoma / Q000201:enzymology / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D010625:Phenylethanolamine N-Methyltransferase
keywords: biomarker; endocrine tumors; metastasis; phenylethanolamine N-methyltransferase; pheochromocytoma/paraganglioma