Can sparsely and heterogeneously expressed proteins be detected using tissue microarrays? A simulation study of the hypoxia marker carbonic anhydrase IX (CA IX) in human soft tissue sarcoma

Pathology, Research and Practice
Kårstein MåseideRichard P Hill

Abstract

Tissue microarrays (TMAs) are often used to evaluate the expression of biological markers across large patient populations. We investigated the number of core biopsies required to accurately classify soft tissue sarcomas with respect to their expression of carbonic anhydrase IX (CA IX), a potential prognostic marker with a sparse and heterogeneous expression pattern. Paraffin-embedded tissue sections from 47 high-grade soft tissue sarcomas had previously been immunostained for CA IX and quantified using image analysis. Sampling of core biopsies was computer simulated by analyzing 2 mm-diameter disc-shaped areas from these images. Core areas were scored as CA IX-positive if the number of CA IX-positive pixels exceeded a threshold value. Overall, 94% of the tumors were correctly classified as CA IX-positive (true-positive rate) if four biopsies at the quadrant centers of each of two sections per tumor were assessed for their CA IX expression with a sensitivity threshold of 0.2%. Similarly, 91% of the tumors were correctly classified as CA IX-positive when only three of the four biopsies per section were assessed. The corresponding false-positive rates were 13% and 11%, respectively. In contrast, sampling of four biopsies at rando...Continue Reading

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Citations

Jul 9, 2010·Diagnostic Pathology·Jeanette E Eckel-PassowEugene D Kwon
Sep 19, 2015·Seminars in Radiation Oncology·Richard P HillBradly G Wouters
Oct 2, 2007·Laboratory Investigation; a Journal of Technical Methods and Pathology·Vladimir V IakovlevDavid W Hedley

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