title: Histology-directed matrix-assisted laser desorption/ionization analysis reveals tissue origin and p53 status of primary liver cancers.
abstract: To date, protein profiles for hepatocellular carcinomas and cholangiocarcinomas have not been systematically evaluated and compared with each other in an unbiased way. Thirty-six hepatocellular carcinomas and adjacent normal tissue samples were analyzed using histology-directed, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). Four cholangiocarcinomas and adjacent normal tissue samples were also evaluated. Tissue samples were sectioned at 10 µm, with 1-3 sections thaw-mounted on a conductive indium tin oxide-coated glass slide. Sinapinic acid was manually deposited on areas of each tissue section enriched by epithelial cells, either tumor or normal, and mass spectra were acquired using a MALDI-time of flight instrument. According to class prediction analysis, average prediction accuracy in test sets (composed of 18 hepatocellular carcinoma-normal pairs) ranged from 93.0 to 95.8%. Cholangiocarcinomas and hepatocellular carcinomas had different protein profiles, as evidenced by average prediction accuracy of >95% in the test set for all classifiers. Permutation P-values for 0.632 + bootstrap cross validated misclassification rates (at feature selection P < 0.001) were less than 0.05 for predicting p53 immunostaining status. We conclude that MALDI MS profiles may be useful in assisting with the diagnosis and the differential diagnosis of primary liver cancers.
authors.affiliation: Korea Research Institute of Standard and Science, Daejeon, Korea.
authors.forename: Young Eun
authors.initials: YE
authors.lastname: Jeon
authors.forename: Seok Cheol
authors.initials: SC
authors.lastname: Lee
authors.forename: Seung Sam
authors.initials: SS
authors.lastname: Paik
authors.forename: Kyeong Geun
authors.initials: KG
authors.lastname: Lee
authors.forename: So Young
authors.initials: SY
authors.lastname: Jin
authors.forename: Hyo Rim
authors.initials: HR
authors.lastname: Kim
authors.forename: Chong Woo
authors.initials: CW
authors.lastname: Yoo
authors.forename: Hye Min
authors.initials: HM
authors.lastname: Park
authors.forename: Sang Yun
authors.initials: SY
authors.lastname: Han
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Choi
authors.forename: Hark Kyun
authors.initials: HK
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000737:chemistry / Q000378:metabolism / Q000556:secondary*; D018281:Cholangiocarcinoma / Q000737:chemistry / Q000378:metabolism / Q000556:secondary*; D005260:Female; D006652:Histological Techniques / Q000379:methods*; D006801:Humans; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism; D009367:Neoplasm Staging; D040901:Proteomics / Q000379:methods; D012189:Retrospective Studies; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53