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
Conclusion of Paper
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.
- Neoplastic - Carcinoma
Analyte Technology Platform Protein Tissue microarray Protein Immunohistochemistry
Classification Pre-analytical Factor Value(s) Biospecimen Aliquots and Components Type of slide Tissue microarray
Immunohistochemistry Specific Targeted peptide/protein ER
Biospecimen Aliquots and Components Biospecimen heterogeneity Biospecimen core