title: Tissue microarray validation: a methodologic study with special reference to lung cancer.
abstract: BACKGROUND
  Although tissue microarray (TMA) studies of histopathologic material have been frequently reported in studies of malignant diseases, the question of sample size (i.e., the diameter and the number of tissue cylinders investigated) has been rarely discussed. This study addresses the methodologic question of sample size in a variety of tumor types.
  
  
  METHODS
  Material from 29 cases of lung carcinoma (small cell, squamous cell, and adenocarcinomas) was examined immunohistochemically for Ki-67 and p53 expression in virtually constructed cylinders of different diameters. The influence of tissue sample size (i.e., different numbers of virtual cylinders) was also investigated. Results from Ki-67 evaluation were analyzed as a continuous variable, whereas p53 expression was scored. p53 evaluations based on scoring in cylinders versus scoring of whole sections were also compared. Furthermore, 10 cases of endometrial and breast carcinomas were evaluated for estrogen receptor, Ki-67, and HER2 by scoring up to five cylinders.
  
  
  CONCLUSIONS
  Tissue cylinders of 0.6 and 1.0 mm diameters were compared and found equally informative about Ki-67 expression (intraclass correlation, 0.96). A statistical approach considering intraindividual and interindividual variation data is presented, indicating that in this specific setting three cylinders per case is an adequate sample size for TMA studies. Further sampling yields only a small gain in accuracy as determined by Ki-67 quantification and p53 scoring (kappa-coefficient, 0.9). For endometrial and breast tissues, TMA scoring of three cylinders yielded excellent agreement (kappa, >0.75) compared with whole-section scoring.
authors.affiliation: School of Health and Medical Sciences, Orebro University, Orebro, Sweden. christina.karlsson@oru.se
authors.forename: Christina
authors.initials: C
authors.lastname: Karlsson
authors.forename: Lennart
authors.initials: L
authors.lastname: Bodin
authors.forename: Karin
authors.initials: K
authors.lastname: Piehl-Aulin
authors.forename: Mats G
authors.initials: MG
authors.lastname: Karlsson
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015203:Reproducibility of Results; D018401:Sample Size; D046888:Tissue Array Analysis / Q000379:methods*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D016159:Tumor Suppressor Protein p53