Tissue Microarray and Imaging

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, 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. 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. 

Key Services

• Automated custom tissue microarray construction
• Array block sectioning and scrolls
• Core punch from paraffin blocks for DNA and RNA work
• Preparation of array slides
• Aperio Digital Pathology Services 
  • Capturing high resolution digital images 
  • Access to web-based digital pathology information management system
  • Access to web-based image analysis algorithms
• Consultation

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

Highlighted Projects

Project Title: Aspirin Use and Colorectal Cancer Survival According to Tumor CD274 (Programmed Cell Death 1 Ligand 1) Expression Status 

PI: Shuji Ogino^DFCI

Blockade of the programmed cell death 1 (PDCD1, PD-1) immune checkpoint pathway can improve clinical outcomes in various malignancies. Evidence suggests that aspirin (a widely used nonsteroidal anti-inflammatory drug) not only prolongs colorectal cancer survival, but can also activate T cell-mediated antitumor immunity and synergize with immunotherapy through inhibition of prostaglandin E2 production. The investigators hypothesized that the survival benefit associated with aspirin might be stronger in colorectal carcinoma with a lower CD274 (PDCD1 ligand 1, PD-L1) expression level that resulted in lower signaling of the immune checkpoint pathway. Using data from 617 patients with rectal and colon cancer in the Nurses' Health Study and the Health Professionals Follow-Up Study, they examined the association of postdiagnosis aspirin use with patient survival in strata of tumor CD274 expression status measured by immunohistochemistry. Results showed that the association of postdiagnosis aspirin use with colorectal cancer-specific survival differed by CD274 expression status ( Pinteraction < .001); compared with aspirin nonusers; multivariable-adjusted hazard ratios for regular aspirin users were 0.16 (95% CI, 0.06 to 0.41) in patients with low CD274 and 1.01 (95% CI, 0.61 to 1.67) in patients with high CD274. In conclusion, the association of aspirin use with colorectal cancer survival is stronger in patients with CD274-low tumors than CD274-high tumors. These findings suggest a differential antitumor effect of aspirin according to immune checkpoint status.

Core Contribution: The Core constructed the high-density colon cancer TMAs (containing tissue cores from 617 tumors) that were immunostained for PD-L1. 

Publication: Hamada T, Cao Y, Qian ZR, Masugi Y, Nowak JA, Yang J, Song M, Mima K, Kosumi K, Liu L, Shi Y, da Silva A, Gu M, Li W, Keum N, Zhang X, Wu K, Meyerhardt JA, Giovannucci EL, Giannakis M, Rodig SJ, Freeman GJ, Nevo D, Wang M, Chan AT, Fuchs CS, Nishihara R, Ogino S.  J Clin Oncol. 2017 Jun 1;35(16):1836-1844. 

Project Title:  Phase 1 Safety, Pharmacokinetic and Pharmacodynamic Study of the Cyclin-Dependent Kinase Inhibitor Dinaciclib Administered Every Three Weeks in Patients with Advanced Malignancies. 

PI: Geoffrey Shapiro^DFCI

Dinaciclib is a potent inhibitor of cell cycle and transcriptional cyclin-dependent kinases. In this Phase 1 study, the investigators evaluated the safety, tolerability and pharmacokinetics of various dosing schedules of dinaciclib in advanced solid tumor patients and assessed pharmacodynamic and preliminary anti-tumour activity. Results showed that dose-limiting toxicities included pancytopenia, neutropenic fever, elevated transaminases, hyperuricemia and hypotension. Pharmacokinetics demonstrated rapid distribution and a short plasma half-life. Dinaciclib suppressed proliferation of stimulated lymphocytes. In skin and tumor biopsies, dinaciclib reduced Rbphosphorylation at CDK2 phospho-sites and modulated expression of cyclin D1 and p53, suggestive of CDK9 inhibition. Eight patients had prolonged stable disease and received between 6 and 30 cycles. Early metabolic responses occurred.

Core Contribution: The Core scanned tissue slides immunostained for various markers (e.g. phospho-Rb, cyclin D1, p53) using the Aperio ScanScope System. Images were then visualized and digitally annotated (as regions of interest, ROIs) using ImageScope software (version 10.0.35.1800, Aperio Technology). ROIs were analyzed using image analysis algorithms (Aperio Technology). 

Publication: Mita MM, Mita AC, Moseley JL, Poon J, Small KA, Jou YM, Kirschmeier P, Zhang D, Zhu Y, Statkevich P, Sankhala KK, Sarantopoulos J, Cleary JM, Chirieac LR, Rodig SJ, Bannerji R, Shapiro GI.Br J Cancer. 2017;117(9):1258-1268.

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."