Construction and validation of tissue microarrays of ductal carcinoma in situ and terminal duct lobular units associated with invasive breast carcinoma.

Author(s): Yang XR, Charette LA, Garcia-Closas M, Lissowska J, Paal E, Sidawy M, Hewitt SM, Rimm DL, Sherman ME

Publication: Diagn Mol Pathol, 2006, Vol. 15, Page 157-61

PubMed ID: 16932071 PubMed Review Paper? No

Purpose of Paper

Conclusion of Paper

Studies

1. Study Purpose

   The purpose of this study was to determine the effects of tumor heterogeneity and section number on IHC staining of ER and PR in TMAs containing breast cancer specimens. The effect of counting rather than subjective quantification of IHC staining was also investigated. The 2 arrays consisted of single 2.0 mM cores selected from representative areas. IHC staining was either classified into 3 categories (less than 10%, 10-50%, or more than 50%) or by intensity based on subjective quantification (negative, weak, intermediate, or strong).

   Summary of Findings:

   In the first sections, 91% of invasive carcinoma specimens had adequate representation in the TMA, defined as more than 10% terminal duct lobular units (TDLU), or more than 10% representation of tumor targets. For non-invasive targets, only 79% of specimens had adequate representation in the TMA. In normal adjacent tissue, core loss occurred only when the target was 2-3 mM in diameter, but in DCIS specimens, arraying failure was more common when the target was in the periphery of the tissue block and was not size related. Representation of tumor tissue was similar for at least the first 100 sections taken from the TMA for invasive tumors, but for non-invasive carcinoma, adequate representation declined after the 30th section, including only 52% of cases by the 100th section. The number of tubules as determined by subjective estimation was concordant with counting results in 70.8% of cases for ER and 79.2% of cases for PR. For the 6 tumor blocks from which multiple TDLU or DCIS cores were available, ER and PR positivity/intensity were generally classified in the same category for all cores, but in some cases, staining positivity or intensity differed by one category.

   Biospecimens

   • Tissue - Breast

   Preservative Types

   • Formalin

   Diagnoses:

   • Neoplastic - Carcinoma
   • Neoplastic - Normal Adjacent

   Platform:

   Analyte	Technology Platform
   Protein	Immunohistochemistry
   Morphology	H-and-E microscopy
   Protein	Tissue microarray

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Biospecimen Aliquots and Components	Aliquot sequential collection	1st section 20'th section 30'th section 40th section 50'th section 60'th section 70'th section 80'th section 90'th section 100'th section
   Immunohistochemistry Specific	Targeted peptide/protein	ER PR
   Preaquisition	Diagnosis/ patient condition	Ductal carcinoma in situ Invasive breast cancer
   Biospecimen Aliquots and Components	Biospecimen heterogeneity	Biospecimen core Biospecimen periphery
   Immunohistochemistry Specific	Data handling	Subjective staining estimation Calculated staining percentage

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