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Tissue Microarray and Imaging Core

October 3, 2013 | eNews

The Tissue Microarray and Imaging Core (TMIC) is dedicated to the construction and evaluation of high-quality tissue microarrays for cancer research. The mission of the TMIC is to generate tissue microarrays by allowing placement of up to 480 0.6 mm diameter tissue samples into a single standard tissue block, allowing hundreds of tumors and samples to be evaluated on a single slide.

The sequencing of the human genome and the development of high-throughput gene expression technologies such as DNA microarrays have led to the discovery of hundreds or thousands of genes with a potential role in neoplastic transformation. Determining whether these genes are clinically relevant has been challenging due, in part, to limited availability of tissue samples necessary to validate these genes. The development of tissue microarray (TMA) technology has enabled the placement of hundreds of minute tissue samples on a single tissue block, thus conserving precious material. In addition, TMAs have increased throughput of in situ analysis because large numbers of tissue samples can be evaluated in a single experiment. Access to this technology and these tissue-based resources is key to advancement of cancer research at DF/HCC.

TMIC services include:

  • Construction of standard and custom TMAs
  • Array block sectioning
  • Preparation of slides
  • Nucleic Acid Isolation from paraffin embedded tissue
  • Immunofluorescent staining
  • Image acquisition & analysis by AQUA
  • Aperio digital pathology services
  • High-throughput isolation of DNA and RNA from formalin-fixed paraffin-embedded tissue cores
  • Consultation

Below are abstracts of publications that resulted from select scientific projects in which the Tissue Microarray and Imaging Core has contributed.

Identification of CDCP1 as a hypoxia-inducible factor 2α (HIF-2α) target gene that is associated with survival in clear cell renal cell carcinoma patient

Principal Investigators: Lewis C. Cantley, PhD (BIDMC), Sabina Signoretti, MD (BWH)

Description of Project: CUB domain-containing protein 1 (CDCP1) is a transmembrane protein that is highly expressed in stem cells and frequently overexpressed and tyrosine-phosphorylated in cancer. CDCP1 promotes cancer cell metastasis. However, the mechanisms that regulate CDCP1 are not well defined. Investigators showed that hypoxia induces CDCP1 expression and tyrosine phosphorylation in hypoxia-inducible factor (HIF)-2α-, but not HIF-1α-, dependent fashion. shRNA knockdown of CDCP1 impaired cancer cell migration under hypoxic conditions, whereas overexpression of HIF-2α promoted the growth of tumor xenografts in association with enhanced CDCP1 expression and tyrosine phosphorylation. Immunohistochemistry analysis of tissue microarray samples from tumors of patients with clear cell renal cell carcinoma showed that increased CDCP1 expression correlates with decreased overall survival. Together, these data support a critical role for CDCP1 as a unique HIF-2α target gene involved in the regulation of cancer metastasis, and suggest that CDCP1 is a biomarker and potential therapeutic target for metastatic cancers.

Contribution of Core: The Core constructed the TMAs utilized in the study to demonstrate the association between the expression of CDCP1 in tumor cells and patient survival.

Publication: Emerling BM, Benes CH, Poulogiannis G, Bell EL, Courtney K, Lui H, Choo-Wing R, Bellinger R, Brown V, Signoretti S, Soltoff SP, and Cantley LC. Proc Natl Acad Sci (U S A). 2013; 110(9):3483-8. PMCID: PMC3587206.

Microbial colonization influences early B-lineage development in the gut lamina propria

Principal Investigators: Frederick W. Alt, PhD (BCH), Scott Rodig, MD, PhD (BWH)  

Description of Project: In Press

Contribution of Core: The Core used the Aperio ScanScope System to digitize tissue slides of mouse gut with immature cells highlighted by TDT stain. The Aperio ruler tool was used to measure distance between crypt base to position of immature cells in gut villi.

Publication: Duane R. Wesemann, Andrew J. Portuguese, Robin M. Meyers, Michael P. Gallagher, Kendra Cluff-Jones, Jennifer M. Magee, Rohit A. Panchakshari, Scott J. Rodig, Thomas B. Kepler & Frederick W. Alt.  Nature. In Press.