title: Tissue microarrays compared with whole sections and biochemical analyses. A subgroup analysis of DBCG 82 b&c.
abstract: BACKGROUND
  The tissue microarray (TMA) technique comprises the potential of significantly reducing time and tissue spent on slicing and performing immunohistochemical (IHC) stainings of paraffin-embedded tumor tissue. Tissue heterogeneity is an argument against using TMAs, which has been dealt with by increasing the size and number of cores punched from each tumor. No consensus exists on the most optimal size, number, and position of TMA cores in the donor paraffin block and no information exist regarding agreement between TMA cores from two different paraffin blocks from the same tumor or between TMA cores and biochemical analyses.
  
  
  METHODS
  A central and a peripheral 1mm core and a whole section from each of 54 paraffin blocks from 27 breast cancers included in a one-institution cohort, and a single 1mm central TMA core, from each breast tumor from 1000 patients included in the DBCG82 b&c trials, were IHC stained for ER, PgR and HER2. In addition, ER and PgR were measured in the DBCG82 b&c trials by a biochemical analysis. Statistical analyses included Kappa statistics, Kaplan-Meier survival curves, Log-rank tests, and Cox regression hazards analyses.
  
  
  CONCLUSIONS
  IHC stainings for ER, PgR, and HER2 showed a substantial agreement between a single 1mm TMA core and the corresponding whole section, between central and peripheral cores, and between cores from two different paraffin blocks from the same tumor. In addition, a fine agreement was found for ER and PgR between IHC stainings of TMA cores and biochemical analyses. Divergence between IHC and biochemical analyses was predominantly due to the chosen thresholds. IHC staining of one 1mm core from each tumor revealed a significant independent prognostic value of PgR and HER2 on overall survival. In conclusion, IHC stainings for ER, PgR, and HER2 of just a single 1mm TMA core seems to be sufficient, as no significant heterogeneity was noticed.
authors.affiliation: Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Kyndi
authors.forename: F B
authors.initials: FB
authors.lastname: Sørensen
authors.forename: H
authors.initials: H
authors.lastname: Knudsen
authors.forename: M
authors.initials: M
authors.lastname: Overgaard
authors.forename: H M
authors.initials: HM
authors.lastname: Nielsen
authors.forename: J
authors.initials: J
authors.lastname: Andersen
authors.forename: J
authors.initials: J
authors.lastname: Overgaard
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis / Q000379:methods; D016612:Paraffin Embedding; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000378:metabolism; D011960:Receptors, Estrogen / Q000032:analysis* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000032:analysis* / Q000378:metabolism
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone