title: Expression Analysis of p16, c-Myc, and mSin3A in Non-small Cell Lung Cancer by Computer Aided Scoring and Analysis (CASA).
abstract: BACKGROUND
  Immunohistochemical analysis (IHC) of tissue microarray (TMA) slides enables large sets of tissue samples to be analyzed simultaneously on a single slide. However, manual evaluation of small cores on a TMA slide is time consuming and error prone.
  
  
  METHODS
  We describe a computer aided scoring and analysis (CASA) method to allow facile and reliable scoring of IHC staining using TMA containing 300 non-small cell lung cancer (NSCLC) cases. In the two previous published papers utilizing our TMA slides of lung cancer we examined 18 proteins involved in the chromatin machinery. We developed our study using more proteins of the chromatin complex and several transcription factors that facilitate the chromatin machinery. Then, a total of 78 antibodies were evaluated by CASA to derive a normalized intensity value that correlated with the overall staining status of the targeting protein. The intensity values for TMA cores were then examined for association to clinical variables and predictive significance individually and with other factors. RESULTs: Using our TMA, the intensity of several protein pairs were significantly correlated with an increased risk of death in NSCLC. These included c-Myc with p16, mSin3A with p16 and c-Myc with mSinA. Predictive values of these pairs remained significant when evaluated based on standard IHC scores.
  
  
  CONCLUSIONS
  Our results demonstrate the usefulness of CASA as a valuable tool for systematic assessment of TMA slides to identify potential predictive biomarkers using a large set of primary human tissues.
authors.forename: Arash
authors.initials: A
authors.lastname: Salmaninejad
authors.forename: Mehrdad Asghari
authors.initials: MA
authors.lastname: Estiar
authors.forename: Rajbir K
authors.initials: RK
authors.lastname: Gill
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Shih
authors.forename: Stephen
authors.initials: S
authors.lastname: Hewitt
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Junya
authors.initials: J
authors.lastname: Fukuoka
authors.forename: Konstantin
authors.initials: K
authors.lastname: Shilo
authors.forename: Abbas
authors.initials: A
authors.lastname: Shakoori
authors.forename: Jin
authors.initials: J
authors.lastname: Jen
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D001330:Electronic Data Processing; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D056264:Sin3 Histone Deacetylase and Corepressor Complex