title: Tissue microarray and digital image analysis: a methodological study with special reference to the microenvironment in Hodgkin lymphoma.
abstract: OBJECTIVE
  Cancer research has moved from solely investigating the tumour cells to also including analysis of the tumour microenvironment; however, the methods utilized have not been evaluated for this change. The aim of this study was to compare tissue microarrays (TMA) to whole tissue sections (WS) with regard to cells in the tumour microenvironment. Manual evaluation and digital image analyses (DIA) were utilized and also compared.
  
  
  RESULTS
  TMA slides from 117 Hodgkin lymphoma patients were immunostained for forkhead box protein 3 (FoxP3) [identifying regulatory T cells (T(reg) )], and 39 corresponding WS were also analysed. Manual evaluation and DIA were utilized for all patients on both the TMA and the WS. A correlation coefficient of 0.83 was obtained for the proportion of T(reg) in TMA versus WS using manual evaluation and a correlation coefficient of 0.77 with DIA. T(reg) counts using manual evaluation correlated in turn with DIA, with a coefficient of 0.79 for the 117 TMA sections and 0.65 for the 39 WS.
  
  
  CONCLUSIONS
  Because a high correlation was observed between TMA and WS, TMA can be utilized when evaluating cells in the tumour microenvironment. DIA appears to provide a reliable measurement method, provided that manual control of the tumour slides is conducted.
authors.affiliation: Department of Radiology, Oncology and Radiation Science, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden. ingrid.glimelius@onkologi.uu.se
authors.forename: Ingrid
authors.initials: I
authors.lastname: Glimelius
authors.forename: Fredrik
authors.initials: F
authors.lastname: Qvarnström
authors.forename: Martin
authors.initials: M
authors.lastname: Simonsson
authors.forename: Anders
authors.initials: A
authors.lastname: Ekwall
authors.forename: Karin E
authors.initials: KE
authors.lastname: Smedby
authors.forename: Daniel
authors.initials: D
authors.lastname: Molin
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Amini
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D008297:Male; D008875:Middle Aged; D046888:Tissue Array Analysis / Q000379:methods*; D059016:Tumor Microenvironment; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors