The impact of the number of cores on tissue microarray studies investigating prostate cancer biomarkers.

Author(s): Tennstedt P, Köster P, Brüchmann A, Mirlacher M, Haese A, Steuber T, Sauter G, Huland H, Graefen M, Schlomm T, Minner S, Simon R

Publication: Int J Oncol, 2012, Vol. 40, Page 261-8

PubMed ID: 21956230 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 scoring methods and the number of TMA cores analyzed on Ki67 and p53 immunostaining results in prostate cancer specimens. The percentage of Ki67 immunostaining was evaluated based on multiple categories while p53 immunostaining was categorized as positive (>1% staining) or negative.

   Summary of Findings:

   Core loss amounted to 1.9, 1.4, and 2.1% of cores for each of 3 TMAs initially containing 3,261 cores. Further, lack of adequate cancer cells was observed in 20.5, 35.0, and 30.5% of the cores for each of the 3 TMAs making them non-informative. The percentage of Ki67 immunopositive cells was linked to the number of analyzable cores. Cases with 3 analyzable cores showed an average of 5.3% Ki67 immunopositive cells while tumors with only 1 analyzable core had an average of 4.1% Ki67 immunopositive staining (p<0.0001). Further, a higher percentage of p53 positivity was observed among cases where 3 analyzable cores were available (3.8%) as opposed to just 1 or 2 cores (1.9%, p=0.003). When only tumors for which 3 informative cores existed were further analyzed, no differences in clinical significance of Ki67 immunostaining were observed when all 3 cores were averaged, when only the highest Ki67 score was considered, or when tumors were classified as positive when at least one core was scored as positive. Ki67 immunostaining was significantly related to biochemical tumor recurrence whether core scores were considered individually, 3 scores were averaged, or just the highest score was considered. Further, there were no differences in the relation of Ki67 immunostaining to biochemical tumor recurrence when levels were defined by quartiles (0-25%, 25-50%, 50-75%, 75-100%) or by arbitrary cutoffs (negative, <10%, 10-20%, 20-100%). p53 immunostaining was related to early prostate specific antigen (PSA) recurrence whether each TMA was considered individually or the tumor was classified as positive based on scoring of at least 1 of 3 cores as positive.

   Biospecimens

   • Tissue - Prostate

   Preservative Types

   • Formalin

   Diagnoses:

   • Normal
   • Neoplastic - Carcinoma

   Platform:

   Analyte	Technology Platform
   Protein	Immunohistochemistry
   Protein	Tissue microarray

   Pre-analytical Factors:

   Classification	Pre-analytical Factor	Value(s)
   Biospecimen Aliquots and Components	Aliquot size/volume	1 core evaluated 2 cores evaluated 3 cores evaluated
   Immunohistochemistry Specific	Targeted peptide/protein	Ki67 p53 Cytokeratins
   Tissue microarray Specific	Data handling	Individual cores considered 3 cores averaged Highest core score considered At least one positive core determined positivity Arbitrary cutoffs used for categorizing Quartiles used for categorizing

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