Tissue Microarray and Imaging Core

The DF/HCC Tissue Microarray and Imaging Core is dedicated to the construction and evaluation of high-quality tissue microarrays for cancer research. Tissue microarrays enable large-scale, high-throughput in situ analysis of gene and protein expression. By providing access to this resource, as well as enabling computer-based image analysis and high-throughput nucleic acid extraction, the Core facilitates translational research and the discovery and validation of novel potential drug targets.

Core services include construction of standard and custom tissue microarrays, consultation, and high-throughput isolation of DNA from formalin-fixed paraffin-embedded tissue cores. The Core also provides web-based digital pathology services using the Aperio system. These services include slide scanning, image viewing and storage, and access to quantitative image analysis algorithms, which facilitate tissue-based research. Additionally, the Core provides access to the Automated Quantitative Analysis (AQUA) system.

Key Services

  • Construction of standard and custom tissue microarrays
  • Preparation of array slides
  • Nucleic acid isolation from paraffin-embedded tissue
  • Aperio digital pathology services
  • Consultation

For more information on services go to: https://pathcore.hms.harvard.edu/catalog/.

Highlighted Projects

Project Title: 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:
 Sabina Signoretti, MD (BWH); Lewis Cantley, PhD (BIDMC)
Description of the Project:

  • CUB domain-containing protein 1 (CDCP1) is a transmembrane protein that is frequently overexpressed and tyrosine-phosphorylated in cancer.
  • Investigators showed that hypoxia induces CDCP1 expression and tyrosine phosphorylation in HIF-2α-, but not HIF-1α-, dependent fashion.
  • Silencing of CDCP1 impaired cancer cell migration, while overexpression of HIF-2α promoted tumor xenografts growth in association with enhanced CDCP1 expression and tyrosine phosphorylation.
  • IHC analysis of TMAs from clear cell RCCs showed that increased CDCP1 expression correlates with decreased overall survival.

Proc Natl Acad Sci (U S A). 2013; 110(9):3483-8. PMCID: PMC3587206.
Contribution of the Core: 
The Core constructed the ccRCC TMAs utilized in the study to demonstrate the association between the expression of CDCP1 in tumor cells and patient survival.

Project Title: Microbial colonization influences early B-lineage development in the gut lamina propria
Principal Investigators: 
Frederick Alt, PhD (BCH); Scott Rodig, MD, PhD (BWH)
Description of the Project:

  • The bone marrow is the principal location of primary immunoglobulin repertoire diversification in mice.
  • Investigators show that early B-cell development also occurs within the mouse intestinal lamina propria (LP).
  • At weaning age in normally housed mice, the LP contains a population of Rag-expressing B-lineage cells that harbour intermediates indicative of ongoing V(D)J recombination.
  • Rag-expressing LP B-lineage cells have similar VH repertoires, but significantly different Vκ repertoires, compared to those of Rag2-expressing bone marrow counterparts.
  • Moreover, colonization of germ-free mice leads to an increased ratio of Igλ-expressing versus Igκ-expressing B cells specifically in the LP.

Nature. 2013 Sep 5;501(7465):112-5. PMID: 23965619.
Contribution of the 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 and position of immature cells in gut villi.

Publication Acknowledgement:

If research supported by this core facility results in publication, please acknowledge this support by including the following in your publication(s):
"We thank Dana-Farber/Harvard Cancer Center in Boston, MA, for the use of the Tissue Microarray Imaging Core, which provided __________ service. Dana-Farber/Harvard Cancer Center is supported in part by an NCI Cancer Center Support Grant # NIH 5 P30 CA06516."