Specialized Histopathology Core

HCC Specialized Histopathology Core

The HCC Specialized Histopathology (SHP) Core has two performance sites: Longwood, directed by Jon Aster and based at the Brigham and Women’s Hospital; and MGH, directed by Anat Stemmer-Rachamimov and based at Massachusetts General Hospital East in Charlestown. SHP provides high-quality, timely, state-of-the-art technical services to investigators working in a variety of experimental organisms, including rodents, fish, and monkeys, as well as with human tissues. The Core performs routine histology, special histochemical stains, advanced staining techniques that include immunohistochemistry, immunofluorescent staining, and in situ hybridization.

The Specialized Histopathology Longwood (SHL) site is a College of American Pathologists (CAP) and CLIA certified facility offering expertise in all aspects of tissue processing, embedding, and staining. SHL also provides skilled sectioning optimized for all spatial transcriptomic platforms, ensuring precise preservation of tissue morphology and molecular integrity for spatially resolved analyses. To request services or schedule a consultation, investigators may submit requests through the portal or contact the SHL Core manager, Teri Bowman, directly at tbowman@mgb.org.

The Specialized Histopathology MGH (SHM) site offers specialized eye pathology services (human and mouse) in addition to tissue processing, embedding, and staining techniques.

To request services, investigators may submit requests through the portal. If you have any questions, please contact the SHM Core manager, Diana Gluhova, directly at dgluhova@mgh.harvard.edu.

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 Harvard Cancer Consortium in Boston, MA, for the use of the Specialized Histopathology Core, which provided ______________________________ service. Harvard Cancer Consortium is supported in part by a NCI Cancer Center Support Grant # NIH 5 P30 CA06516.

• Tissue trimming, cassetting, processing, and embedding
• Cutting and staining of paraffin-embedded and frozen OCT sections
• Immunohistochemistry for both routine and novel markers
• Immunofluorescence for both routine and novel markers
• In situ hybridization using chromogenic detection method (Longwood only)
• All services CAP/CLIA certified (Longwood only)
• Patient Block/Slide Retrieval & Associated Services (Longwood only)
• Spatial genomic sectioning for Xenium, Visium, Codex and MerFish [Longwood Only]

Go to MGB-RCMS for more information on services, to place an order, or to set up a new user account:

Project Title

A neoantigen vaccine generates antitumour immunity in renal cell carcinoma.

Principal Investigators: Toni K. Choueiri (DFCI), Jon C. Aster (BWH), Nir Hacohen (MGH), Bradley A. McGregor (DFCI), Patrick A. Ott (DFCI), Sabina Signoretti (BWH), Catherine J. Wu (DFCI).

Project Abstract (Longwood Site):

Emerging imaging spatial transcriptomics (iST) platforms and coupled analytical methods can recover cell-to-cell interactions, groups of spatially covarying genes, and gene signatures associated with pathological features, and are thus particularly well-suited for applications in formalin fixed paraffin embedded (FFPE) tissues. Here, we benchmarked the performance of three commercial iST platforms on serial sections from tissue microarrays (TMAs) containing 23 tumor and normal tissue types for both relative technical and biological performance. On matched genes, we found that 10x Xenium shows higher transcript counts per gene without sacrificing specificity, but that all three platforms concord to orthogonal RNA-seq datasets and can perform spatially resolved cell typing, albeit with different false discovery rates, cell segmentation error frequencies, and with varying degrees of sub-clustering for downstream biological analyses. Taken together, our analyses provide a comprehensive benchmark to guide the choice of iST method as researchers design studies with precious samples in this rapidly evolving field.​

Contribution of the Core: Preparation of specialty slides for comparative iST studies.

Project Title

Systematic benchmarking of imaging spatial transcriptomics platforms in FFPE tissues.

Principal Investigators: Scott J Rodig (BWH)​

Project Abstract (Longwood Site):

Personalized cancer vaccines (PCVs) can generate circulating immune responses against predicted neoantigens1–6. However, whether such responses can target cancer driver mutations, lead to immune recognition of a patient’s tumour and result in clinical activity are largely unknown. These questions are of particular interest for patients who have tumours with a low mutational burden. Here we conducted a phase I trial (ClinicalTrials.gov identifier NCT02950766) to test a neoantigen-targeting PCV in patients with high-risk, fully resected clear cell renal cell carcinoma (RCC; stage III or IV) with or without ipilimumab administered adjacent to the vaccine. At a median follow-up of 40.2 months after surgery, none of the 9 participants enrolled in the study had a recurrence of RCC. No dose-limiting toxicities were observed. All patients generated T cell immune responses against the PCV antigens, including to RCC driver mutations in VHL, PBRM1, BAP1, KDM5C and PIK3CA. Following vaccination, there was a durable expansion of peripheral T cell clones. Moreover, T cell reactivity against autologous tumours was detected in seven out of nine patients. Our results demonstrate that neoantigen-targeting PCVs in high-risk RCC are highly immunogenic, capable of targeting key driver mutations and can induce antitumour immunity. These observations, in conjunction with the absence of recurrence in all nine vaccinated patients, highlights the promise of PCVs as effective adjuvant therapy in RCC.​

Contribution of the Core: Preparation of specialty slides for comparative iST studies.

Project Title

Immunocompetent murine glioblastoma stem-like cell models exhibiting distinct phenotypes.

Principal Investigators: Samuel D Rabkin (MGH), Anat Stemmer-Rachamimov (MGH) 

Project Abstract (MGH Site):

Background. Glioblastoma (GBM) treatment is hindered by a dearth of representative mouse GBM preclinical models in immunocompetent mice. Here, we characterized 5 murine GBM stem-like cell (mGSC) models derived from lentivirus-induced tumors in transgenic mice that are driven by the activation of the Nf1-Ras signaling pathway and inactivation of Tp53.

Methods. MGSC lines (005, RIG, NF53, C1, and C3) were cultured as spheres in serum-free stem cell media. Whole exome sequencing (WES) was employed to quantify single nucleotide polymorphisms (SNPs). Stem cell properties were characterized by stemness in vitro and tumorigenicity after intracerebral implantation in C57BL/6 mice. Tumor phenotypes and the immune microenvironment were characterized by immunohistochemistry, flow cytometry, and RNA sequencing.

Results. WES revealed a large variation in coding sequence SNPs across mGSC lines (~20-fold), likely influenced by the mixed backgrounds of the parental mice. MGSCs exhibited variable clonogenic sphere formation and CD133 expression levels. In vivo, they consistently initiated lethal malignant gliomas, with median survival ranging from 29 to 82 days, and showed strong CD44 expression and variable invasiveness. The tumor microenvironment featured an abundance of CD68+ macrophages and uniform high PD-L1+ myeloid cells, while T-cell infiltration varied among the models, with low mutation burden C1 and C3 exhibiting fewer tumor-infiltrating T cells.

Conclusions. Upon orthotopic implantation in immunocompetent mice, mGSCs generate tumors characteristic of human GBM. Despite similar strategies to generate these mGSCs, they exhibited a range of phenotypes and immune profiles in mGSC-derived orthotopic tumors. These mGSCs provide new preclinical GBM models for developing GBM immunotherapies.

Contribution of the Core: The core provided processing, embedding, sectioning, and  immunohistochemical staining.

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Longwood Site (BWH)

Core Leadership
Jon Aster, MD, PhD, Director, Core Pathologist
Sabina Signoretti, MD, Associate Pathologist
 

Technical Questions/Project Status
Teri Bowman, Manager
(617) 525-9394
tbowman@mgb.org
Walk-in hours for Drop-Off and Pick-Up Monday-Thursday between 10am to 3:30pm; and Friday by appointment only

MGH Site

Core Leadership
Anat Stemmer-Rachamimov, MD, Core Co-Director
Chin-Lee Wu, MD, PhD, Associate Pathologist
David Louis, MD, Consultant

Technical Questions/Project Status
Diana Gluhova, Manager
(617) 726-5510
DGLUHOVA@mgh.harvard.edu
Walk-in hours for Drop-Off and Pick-Up Monday-Friday between 10:00am to 3:30pm.

Longwood and MGH Site

Administrative/Billing Concerns
Lauri Wyner, Research Cores Director of Administration
lauri_wyner@hms.harvard.edu