NIH, National Cancer Institute, Division of Cancer Treatment and Diagnosis (DCTD) NIH - National Institutes of Health National Cancer Institute DCTD - Division of Cancer Treatment and Diagnosis

Tissue microarrays for rapid linking of molecular changes to clinical endpoints.

Author(s): Torhorst J, Bucher C, Kononen J, Haas P, Zuber M, Köchli OR, Mross F, Dieterich H, Moch H, Mihatsch M, Kallioniemi OP, Sauter G

Publication: Am J Pathol, 2001, Vol. 159, Page 2249-56

PubMed ID: 11733374 PubMed Review Paper? No

Purpose of Paper

The purpose of this paper was to compare immunohistochemical (IHC) staining results between tissue microarrays (TMAs) and whole sections.

Conclusion of Paper

Of the arrayed cores, 70.3-76.5% gave interpretable staining for estrogen receptor (ER), progesterone receptor (PR) and p53, but when multiple arrays were combined, the percentage of specimens for which there was an interpretable result increased. ER IHC staining was generally similar among the 4 cores taken from each tumor and agreed with IHC results from whole sections. PR staining was much more heterogeneous and required combining results from 4 cores to achieve a similar result to that in whole sections. p53 staining was also somewhat heterogeneous, but combining results from the 4 cores did not achieve similar positivity percentages as found in whole sections. The percentage of positive results for PR, ER and p53 staining did not depend on location of core within the biospecimen.

Studies

  1. Study Purpose

    The purpose of this study was to compare IHC staining results between TMAs and whole sections and to determine the effects of TMA core location on ER, PR, and p53 positivity in breast tumors. This study included 4 TMAs: 1 consisting of cores taken from the tumor center and 3 using cores taken from the tumor periphery. ER and PR staining were considered positive when nuclear staining was observed in at least 10% of tumor cells, and p53 positivity was defined as moderate nuclear staining in 20% or more of tumor cells. 3 sections from each tumor block or TMA were analyzed.

    Summary of Findings:

    Of the arrayed cores, 70.3-76.5% gave interpretable staining for ER, PR and p53, but the reasons were unspecified; however, by combining multiple arrays the percentage of specimens for which there was an interpretable result increased to 86.4-93.1% with 2 cores, 92.2-95.5% with 3 cores, and 94.9-96.9% with 4 cores. 78.9-80.8% of tumors were classified as ER positive using sections of the 4 TMAs, and 79.8% of cases were classified as such when whole tissue sections were evaluated. When the results from the 4 cores were compared, 8.8% of cases had heterogeneous findings for ER. PR staining was positive in 41.1-53.1% of cases on the 4 TMAs, but in 60.3% of large sections. The 4 arrays showed different PR staining results in 28.9% of cases, and combining results from the multiple arrays increased the percentage of PR positive tumors to 60%. p53 positivity was found in 15.2-20.9% of tumors on the 4 TMAs with 11.3% of specimens having discordant results between the arrays. The p53 positivity rate increased to 24.1% when data from all 4 arrays were combined, but 42.8% of tumors were classified as p53 positive based on staining of whole sections. Further review showed that the discrepant cases had faint to moderate staining in 15-30% of the whole section, and that poor prognosis was linked to p53 positivity on the TMAs, but not to p53 positivity in only the whole sections. The percentage of positivity for PR, ER and p53 did not depend on location of core within the specimen. Finally, loss of ER or PR staining on TMAs or large sections was associated with a poor prognosis.

    Biospecimens
    Preservative Types
    • Formalin
    Diagnoses:
    • Neoplastic - Carcinoma
    Platform:
    AnalyteTechnology Platform
    Protein Tissue microarray
    Protein Immunohistochemistry
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Biospecimen Aliquots and Components Type of slide Tissue microarray
    Whole section
    Immunohistochemistry Specific Targeted peptide/protein ER
    PR
    p53
    Biospecimen Aliquots and Components Biospecimen heterogeneity Biospecimen core
    Biospecimen periphery

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