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Usefulness of Automatic Quantification of Immunochemical Staining on Whole Tumor Sections for Correlation with Oncological Small Animal PET Studies: An Example with Cell Proliferation, Glucose Transporter 1 and FDG

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Abstract

Aim

To highlight the use of automatic quantification of immunochemical staining on digitized images of whole tumor sections in preclinical positron emission tomography (PET) studies.

Materials and methods

Xenografted human testicular tumors (36) were imaged with 2-deoxy-2[F-18]fluoro-d-glucose (FDG) small animal PET (SA-PET). Tumor cell proliferation and glucose transportation were assessed with cyclin A and Glut-1 immunostaining. Tumor slides were digitized and processed with PixCyt® software enabling whole slide quantification, then compared with junior and senior pathologist manual scoring. Manual and automatic quantification results were correlated to FDG uptake.

Results

For cyclin A, inter- and intra-observer agreement for manual scoring was 0.52 and 0.72 and concordance between senior pathologist and automatic quantification was 0.84. Correlations between Tumor/Background ratio and tumor cell proliferation assessed by automatic quantification, junior and senior pathologists were 0.75, 0.55, and 0.61, respectively. Correlation between Tumor/Background ratio and Glut-1 assessed by automatic quantification was 0.74.

Conclusion

Automatic quantification of immunostaining is a valuable tool to overcome inter- and intra-observer variability for correlation of cell proliferation or other markers with tumor tracer uptake.

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Acknowledgments

The authors wish to thank Edwige Deslandes for cell line management, Mélanie Briand for her help during small animal PET acquisitions, Natacha Heutte for the statistical studies and Mylene Brécin for her help during whole slide scanning. Heather Costil is thanked for manuscript editing.

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Authors and Affiliations

  1. GRECAN, EA 1772, François Baclesse Comprehensive Cancer Center and Caen University, Caen, France

    Nicolas Aide, Alexandre Labiche, Paulette Herlin, Laurent Poulain, Soizic Dutoit & Pascal Gauduchon

  2. Pathology Department, François Baclesse Comprehensive Cancer Center, Caen, France

    Maria Paciencia & Jacques Chasle

  3. LIMP, Tenon Hospital, AP-HP and Pierre et Marie Curie University (Paris6), Paris, France

    Nicolas Aide & Françoise Montravers

  4. Nuclear Medicine Department, François Baclesse Comprehensive Cancer Center, Avenue Général Harris, 14076, Caen cedex 5, France

    Nicolas Aide

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  1. Nicolas Aide
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  2. Alexandre Labiche
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  3. Paulette Herlin
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  4. Maria Paciencia
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  9. Jacques Chasle
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Corresponding author

Correspondence to Nicolas Aide.

Additional information

This work was supported by a grant from the French Ligue Contre le Cancer, Comité du Calvados. Alexandre Labiche received a fellowship from the Ligue Contre le Cancer, Comité de la Manche.

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Aide, N., Labiche, A., Herlin, P. et al. Usefulness of Automatic Quantification of Immunochemical Staining on Whole Tumor Sections for Correlation with Oncological Small Animal PET Studies: An Example with Cell Proliferation, Glucose Transporter 1 and FDG. Mol Imaging Biol 10, 237–244 (2008). https://doi.org/10.1007/s11307-008-0144-5

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  • DOI: https://doi.org/10.1007/s11307-008-0144-5

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