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

Xiaohong Rose Yang, Lori A. Charette, Montserrat Garcia-Closas, Jolanta Lissowska, Edina Paal, Mary Sidawy, Stephen M. Hewitt, David L. Rimm, Mark E. Sherman

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Construction of tissue microarrays (TMAs) to efficiently characterize large sets of noninvasive epithelial lesions in the breast by immunohistochemistry is an appealing investigative approach, but presents technical challenges. We report methodologic studies performed to optimize methods for building TMAs from noninvasive breast tissues collected in a large case-control study of breast cancer. Using a manual arraying technique with 2.0-mm diameter needles, we constructed TMAs from specimens obtained from 32 women with breast cancer containing the following targets: (1) 28 terminal duct lobular units (TDLUs); (2) 28 ductal carcinomas in situ, and (3) 23 invasive carcinomas. Using careful target selection, we achieved representation of ∼80% of noninvasive targets with sustained preservation through section 30 of the TMAs. Immunohistochemical staining of TDLU targets demonstrated positive staining for estrogen receptor (ER) in 30.8% of tubules and for progesterone receptor (PR) in 50.0%. To establish an efficient method to evaluate staining results in TDLUs, we created a categorical scoring system to approximate the percentage of tubules containing positive stained cells (<10%, 10% to 50%, ≥50%), and compared the results with those obtained by tubule counting. Comparison between the two methods demonstrated exact agreement for 70.8% of ER and 79.2% of PR stains without two-category discrepancies. ER/PR expression levels in multiple (up to 4) noninvasive targets of the same tissue type (TDLU or DCIS) from a single block showed good correlation. These data suggest that it is feasible to produce TMAs of noninvasive breast structures, albeit with careful selection of targets, and that immunostains of such cores may permit efficient immunohistochemical characterization of peritumoral tissues. Additional exploration of this approach is needed.

Original languageEnglish (US)
Pages (from-to)157-161
Number of pages5
JournalDiagnostic Molecular Pathology
Volume15
Issue number3
DOIs
StatePublished - Sep 2006

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Carcinoma, Intraductal, Noninfiltrating
Breast Neoplasms
Progesterone Receptors
Estrogen Receptors
Breast
Staining and Labeling
Needles
Case-Control Studies
Coloring Agents
Immunohistochemistry
Carcinoma

Keywords

  • Breast cancer
  • DCIS
  • TDLUs
  • Tissue microarrays (TMAs)

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Construction and validation of tissue microarrays of ductal carcinoma in situ and terminal duct lobular units associated with invasive breast carcinoma. / Yang, Xiaohong Rose; Charette, Lori A.; Garcia-Closas, Montserrat; Lissowska, Jolanta; Paal, Edina; Sidawy, Mary; Hewitt, Stephen M.; Rimm, David L.; Sherman, Mark E.

In: Diagnostic Molecular Pathology, Vol. 15, No. 3, 09.2006, p. 157-161.

Research output: Contribution to journalArticle

Yang, Xiaohong Rose ; Charette, Lori A. ; Garcia-Closas, Montserrat ; Lissowska, Jolanta ; Paal, Edina ; Sidawy, Mary ; Hewitt, Stephen M. ; Rimm, David L. ; Sherman, Mark E. / Construction and validation of tissue microarrays of ductal carcinoma in situ and terminal duct lobular units associated with invasive breast carcinoma. In: Diagnostic Molecular Pathology. 2006 ; Vol. 15, No. 3. pp. 157-161.
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AB - Construction of tissue microarrays (TMAs) to efficiently characterize large sets of noninvasive epithelial lesions in the breast by immunohistochemistry is an appealing investigative approach, but presents technical challenges. We report methodologic studies performed to optimize methods for building TMAs from noninvasive breast tissues collected in a large case-control study of breast cancer. Using a manual arraying technique with 2.0-mm diameter needles, we constructed TMAs from specimens obtained from 32 women with breast cancer containing the following targets: (1) 28 terminal duct lobular units (TDLUs); (2) 28 ductal carcinomas in situ, and (3) 23 invasive carcinomas. Using careful target selection, we achieved representation of ∼80% of noninvasive targets with sustained preservation through section 30 of the TMAs. Immunohistochemical staining of TDLU targets demonstrated positive staining for estrogen receptor (ER) in 30.8% of tubules and for progesterone receptor (PR) in 50.0%. To establish an efficient method to evaluate staining results in TDLUs, we created a categorical scoring system to approximate the percentage of tubules containing positive stained cells (<10%, 10% to 50%, ≥50%), and compared the results with those obtained by tubule counting. Comparison between the two methods demonstrated exact agreement for 70.8% of ER and 79.2% of PR stains without two-category discrepancies. ER/PR expression levels in multiple (up to 4) noninvasive targets of the same tissue type (TDLU or DCIS) from a single block showed good correlation. These data suggest that it is feasible to produce TMAs of noninvasive breast structures, albeit with careful selection of targets, and that immunostains of such cores may permit efficient immunohistochemical characterization of peritumoral tissues. Additional exploration of this approach is needed.

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