Nature Medicine11, 95 - 101 (2004)
Published online: 26 December 2004; | doi:10.1038/nm1169
Tissue-print and print-phoresis as platform technologies for the molecular analysis of human surgical specimens: mapping tumor invasion of the prostate capsule
Sandra M Gaston1, Marc A Soares1, M Minhaj Siddiqui2, Dang Vu1, Jung M Lee1, Dana L Goldner1, Mark J Brice1, Jennifer C Shih1, Melissa P Upton3, George Perides4, Jovanna Baptista5, Philip T Lavin5, B Nicolas Bloch6, Elizabeth M Genega3, Mark A Rubin7
& Robert E Lenkinski6
1
Department of Surgery, Division of Urology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
2
Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.
3
Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
4
Department of Surgery, New England Medical Center, 750 Washington Street, Boston, Massachusetts 02111, USA.
5
Averion (Biostatistics), 4 California Avenue, Framingham, Massachusetts 01701, USA.
6
Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
7
Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
Molecular profiling of human biopsies and surgical specimens is frequently complicated by their inherent biological heterogeneity and by the need to conserve tissue for clinical diagnosis. We have developed a set of novel 'tissue print' and 'print-phoresis' technologies to facilitate tissue and tumor-marker profiling under these circumstances. Tissue printing transfers cells and extracellular matrix components from a tissue surface onto nitrocellulose membranes, generating a two-dimensional anatomical image on which molecular markers can be visualized by specific protein and RNA- and DNA-detection techniques. Print-phoresis is a complementary new electrophoresis method in which thin strips from the print are subjected to polyacrylamide gel electrophoresis, providing a straightforward interface between the tissue-print image and gel-based proteomic techniques. Here we have utilized these technologies to identify and characterize markers of tumor invasion of the prostate capsule, an event generally not apparent to the naked eye that may result in tumor at the surgical margins ('positive margins'). We have also shown that tissue-print technologies can provide a general platform for the generation of marker maps that can be superimposed directly onto histopathological and radiological images, permitting molecular identification and classification of individual malignant lesions.
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