Tissue microarrays compared with whole sections and biochemical analyses. A subgroup analysis of DBCG 82 b&c.

Author(s): Kyndi M, Sørensen FB, Knudsen H, Overgaard M, Nielsen HM, Andersen J, Overgaard J

Publication: Acta Oncol, 2008, Vol. 47, Page 591-9

PubMed ID: 18465327 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   Proportional agreement (represented by the Kappa value, k) between receptor case status was determined by immunohistochemical analysis of (1) a 1.0 mm TMA core and a corresponding whole section, (2) 1.0 mm TMA cores taken from the center or periphery of the same paraffin block, (3) 1.0 mm cores taken from the same location of two different paraffin blocks, and (4) whole sections from two different paraffin blocks. A total of 108 paraffin blocks from 27 patients were examined.

   Summary of Findings:

   Proportional agreements in receptor case status among TMA cores and corresponding whole sections were antigen-dependent. When a corresponding TMA core and whole section were compared almost perfect agreements were reported for ER (k=0.81), and substantial agreements for PR (k=0.70) and HER-2 (k=0.67). Similarly, comparisons between TMA cores punched at the core or periphery of a paraffin block revealed almost perfect agreement for ER (k=0.83) and PR (k=0.80) case status, and substantial agreement for HER-2 (k=0.73). When TMA cores taken from two different paraffin blocks were compared, the proportional agreement was higher among cores taken from the center as opposed to the periphery for all three antigens, ER (k=0.89 versus 0.77), PR (k=0.65 versus 0.54), and HER-2 (k=0.78 versus 0.69). Agreements among TMA cores did not increase when all four TMA cores were compared for ER (k=0.83), PR (k=0.67), or HER-2 (k=0.73). Importantly, agreements among TMA cores were lower than agreements between whole sections from two different paraffin blocks, which approached perfect for all three antigens investigated (ER, k=0.92; PR, k=1.00; HER-2, k=0.95). An additional source of variability included discrepancies among observers. Although the Kappa values reported above represent an average, observer values were reported separately in the manuscript and interobserver agreement was determined to be substantial for both TMA cores (k=0.75) and whole sections (k=0.65). The percent agreement between a TMA core and a corresponding whole section was reported as 62% and 67% for ER and PR respectively, although the case status criteria differed between proportional agreement analysis (for which a positive case was defined as nuclear staining in greater than 10% of invasive tumor cells) and percent agreement (for which a positive case was defined as nuclear staining in more than 10 or 50 invasive tumor cells in a TMA core or whole section, respectively).

   Biospecimens

   • Tissue - Breast

   Preservative Types

   • Formalin

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   Protein	Immunohistochemistry
   Protein	Tissue microarray

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Biospecimen Aliquots and Components	Biospecimen heterogeneity	Biospecimen core Biospecimen periphery
   Biospecimen Aliquots and Components	Aliquot size/volume	Single paraffin block Two paraffin blocks
   Biospecimen Aliquots and Components	Type of slide	Tissue microarray core Whole tissue section
   Immunohistochemistry Specific	Targeted peptide/protein	ER PR HER-2

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2. Study Purpose

   The purpose of this study was to determine if ER and PR case status can accurately be determined by immunohistochemistry of a single 1.0 mm TMA core. The percentage of ER and PR positive and negative cases determined by immunohistochemistry and the Dextran Coated Charchoal (DCC) assay were compared in 580 and 534 patients, respectively. Criteria for positive receptor status by immunohistochemistry and the DCC assay was set at nuclear staining in greater than 10% of invasive tumor cells or 10 fmol/mg cytosol protein, respectively.

   Summary of Findings:

   Comparison of ER and PR status by immunohistochemical analysis of a single TMA core and biochemical quantification of free cytolosolic ER and PR in tumor homogenates reveals a 85% agreement for ER status (k=0.64) and a 82% agreement for PR (k=0.62). The majority of discrepant cases were characterized by low DCC values and a negative immunohistochemistry status.

   Biospecimens

   • Tissue - Breast

   Preservative Types

   • Formalin

   Diagnoses:

   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   Protein	Immunohistochemistry
   Protein	Tissue microarray
   Protein	Receptor binding

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Immunohistochemistry Specific	Technology platform	Immunohistochemistry Dextran Coated Charcoal Assay

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