Shannon McCall

Overview:

As Vice Chair for Translational Research in the Department of Pathology, I am involved in numerous translational cancer research projects that rely on the study of human biological samples.  I am the director of the Duke BioRepository & Precision Pathology Center (Duke BRPC), a shared resource of the School of Medicine and the Duke Cancer Institute.  I serve as the PI for the National Cancer Institute's Cooperative Human Tissue Network Southern Division (a five-year UM1 grant), which lives in the Duke BRPC.  My own area of research interest is gastrointestinal tract metaplasias and their relationship to carcinogenesis, particularly in the upper GI tract.

Positions:

Associate Professor of Pathology

Pathology
School of Medicine

Associate Professor in Surgery

Surgery, Surgical Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 1996

North Carolina State University

M.D. 2000

Duke University

Anatomic and Clinical Pathology, American Board of Pathology (ABPath)

American Board of Pathology

Clinical Informatics, American Board of Pathology (ABPath)

American Board of Pathology

Resident, Pathology

Duke University

Chief Resident, Pathology

Duke University

Grants:

Mutation analysis of pap smear samples and associated tissues for ovarian cancer diagnostics

Administered By
Pathology
Role
Principal Investigator
Start Date
End Date

Cooperative Human Tissue Network Support through Duke's BioRepository & Precision Pathology Center

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

The genetics of hepatosplenic T cell lymphoma

Administered By
Medicine, Hematologic Malignancies and Cellular Therapy
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Empowering Duke's Precision Pathology Center with Quantitative Image Analysis to Support Discovery, Diagnostic Assay Development, and Immune Cell Monitoring

Administered By
Pathology
Role
Principal Investigator
Start Date
End Date

Lung Squamous Cell Carcinoma: Validation of Molecular Signatures of Prognosis

Administered By
Surgery, Cardiovascular and Thoracic Surgery
Role
Pathologist
Start Date
End Date

Publications:

State of the Art: Toward Improving Outcomes of Lung and Liver Tumor Biopsies in Clinical Trials-A Multidisciplinary Approach.

PURPOSE: National Cancer Institute (NCI)-sponsored clinical trial network studies frequently require biopsy specimens for pharmacodynamic and molecular biomarker analyses, including paired pre- and post-treatment samples. The purpose of this meeting of NCI-sponsored investigators was to identify local institutional standard procedures found to ensure quantitative and qualitative specimen adequacy. METHODS: NCI convened a conference on best biopsy practices, focusing on the clinical research community. Topics discussed were (1) criteria for specimen adequacy in the personalized medicine era, (2) team-based approaches to ensure specimen adequacy and quality control, and (3) risk considerations relevant to academic and community practitioners and their patients. RESULTS AND RECOMMENDATIONS: Key recommendations from the convened consensus panel included (1) establishment of infrastructure for multidisciplinary biopsy teams with a formalized information capture process, (2) maintenance of standard operating procedures with regular team review, (3) optimization of tissue collection and yield methodology, (4) incorporation of needle aspiration and other newer techniques, and (5) commitment of stakeholders to use of guideline documents to increase awareness of best biopsy practices, with the goal of universally improving tumor biopsy practices.
Authors
Levy, EB; Fiel, MI; Hamilton, SR; Kleiner, DE; McCall, SJ; Schirmacher, P; Travis, W; Kuo, MD; Suh, RD; Tam, AL; Islam, SU; Ferry-Galow, K; Enos, RA; Doroshow, JH; Makhlouf, HR
MLA Citation
Levy, Elliot B., et al. “State of the Art: Toward Improving Outcomes of Lung and Liver Tumor Biopsies in Clinical Trials-A Multidisciplinary Approach.J Clin Oncol, vol. 38, no. 14, May 2020, pp. 1633–40. Pubmed, doi:10.1200/JCO.19.02322.
URI
https://scholars.duke.edu/individual/pub1434107
PMID
32134701
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
38
Published Date
Start Page
1633
End Page
1640
DOI
10.1200/JCO.19.02322

Characterization of tumor mutation burden, PD-L1 and DNA repair genes to assess relationship to immune checkpoint inhibitors response in metastatic renal cell carcinoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have expanded treatment options for metastatic renal cell carcinoma (mRCC); however, there are limited predictive biomarkers for response to ICIs in this indication, with programmed death-ligand 1 (PD-L1) status demonstrating little predictive utility in mRCC. While predictive of ICI response in other tumor types, the utility of tumor mutation burden (TMB) in mRCC is unclear. Here, we assess TMB, loss of antigen presentation genes and PD-L1 status correlated with outcomes to ICI treatment in mRCC. METHODS: Tumor samples from 34 patients with mRCC treated with ICI therapy at Duke Cancer Institute were retrospectively evaluated using Personal Genome Diagnostics elio tissue complete (RUO version), a tumor genomic profiling assay for somatic variants, TMB, microsatellite status and genomic status of antigen presentation genes. Tumor samples were also analyzed with the Dako 28-8 PD-L1 immunohistochemistry assay. Deidentified clinical information was extracted from the medical record, and tumor response was evaluated based on the Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1 criteria. RESULTS: Patients were stratified by overall response following ICI therapy and designated as progressive disease (PD; n=18) or disease control groups (DC; n=16). TMB scores ranged from 0.36 to 12.24 mutations/Mb (mean 2.83 mutations/Mb) with no significant difference between the PD and DC groups (3.01 vs 2.63 mutations/Mb, respectively; p=0.7682). Interestingly, 33% of PD patients displayed loss of heterozygosity of major histocompatibility complex class I genes (LOH-MHC) vs 6% of DC patients. Nine of 34 samples were PD-L1-positive (4 in the PD group; 5 in the DC group), suggesting no correlation between PD-L1 expression and response to ICI therapy. Notably, the DC group displayed an enrichment of mutations in DNA repair genes (p=0.04), with 68.8% exhibiting at least one mutated homologous recombination repair (HRR)-related gene compared with only 38.9% of the PD group (p=0.03). CONCLUSIONS: Overall, neither TMB nor PD-L1 correlated with ICI response and TMB was not significantly associated with PD-L1 expression. The higher incidence of LOH-MHC in PD group suggests that loss of antigen presentation may restrict response to ICIs. Separately, enrichment of HRR gene mutations in the DC group suggests potential utility in predicting ICI response and a potential therapeutic target, warranting future studies.
Authors
Labriola, MK; Zhu, J; Gupta, R; McCall, S; Jackson, J; Kong, EF; White, JR; Cerqueira, G; Gerding, K; Simmons, JK; George, D; Zhang, T
MLA Citation
Labriola, Matthew Kyle, et al. “Characterization of tumor mutation burden, PD-L1 and DNA repair genes to assess relationship to immune checkpoint inhibitors response in metastatic renal cell carcinoma.J Immunother Cancer, vol. 8, no. 1, Mar. 2020. Pubmed, doi:10.1136/jitc-2019-000319.
URI
https://scholars.duke.edu/individual/pub1435838
PMID
32221016
Source
pubmed
Published In
Journal for Immunotherapy of Cancer
Volume
8
Published Date
DOI
10.1136/jitc-2019-000319

Incidental urothelial rest within the vermiform appendix of a paediatric male patient: an extremely rare entity.

Authors
Schild, MH; Leckey, BD; Coulas, A; McCall, S
MLA Citation
Schild, Michael H., et al. “Incidental urothelial rest within the vermiform appendix of a paediatric male patient: an extremely rare entity.Bmj Case Rep, vol. 13, no. 1, Jan. 2020. Pubmed, doi:10.1136/bcr-2019-233530.
URI
https://scholars.duke.edu/individual/pub1427204
PMID
31919071
Source
pubmed
Published In
Bmj Case Reports
Volume
13
Published Date
DOI
10.1136/bcr-2019-233530

Characterization of genomic alterations as biomarkers of immune checkpoint inhibitor (ICI) response in metastatic urothelial carcinoma (mUC).

<jats:p> 400 </jats:p><jats:p> Background: ICIs have expanded therapeutic options for mUC patients (pts); however, biomarkers such as PD-L1 have not served as reliable predictors of treatment efficacy. High tumor mutation burden (TMB) has been previously described as a potential biomarker for predicting ICI response in several indications, but its utility is still being explored in mUC. Here, we compare the genomic landscapes and clinical outcomes of mUC pts following ICI therapy using an investigational solid tissue-based next-generation sequencing assay to assess TMB and identify genetic correlates of ICI response. Methods: 20 pts with mUC treated with ICIs at Duke Cancer Institute were identified. Tumor samples were retrospectively evaluated with a Personal Genome Diagnostics Assay for somatic variants across &gt; 500 genes, as well as TMB and microsatellite status. Tumor samples were also stained for PD-L1 status using the Dako 22C3 IHC assay. Deidentified clinical information was extracted from the medical record and tumor response was evaluated using RECIST 1.1 criteria. Results: Pts were grouped by overall response following ICI therapy as either responders (“R”, n = 6) or non-responders (“NR”, n = 13). Pts exhibited a wide range of TMB scores (0.7 to 30.4 mutations/Mb), with a mean TMB score of 9.60 vs. 3.87 mut/Mb in R vs NR groups, respectively; however, this difference was not statistically significant ( p = 0.284). 18 pts were evaluated for PD-L1 status, with only 2 positive samples (one in each group). Rs had significantly more mutations in histone methylation genes (KDM6A, KMT2C, and KMT2D), (67% vs 15% in NRs, p = 0.0039). FGFR3 mutations were also more frequent in R vs NR (67% vs 5%, p = 0.0339). Finally, there was a higher frequency of mutations in TP53 and BRCA1 in the NRs. Conclusions: In this mUC cohort, neither TMB nor PD-L1 correlated with response to ICI therapy. Histone modifying genes and FGFR3 mutations were more frequent in responders, whereas BRCA1 and TP53 mutations were enriched in non-responders, warranting future prospective studies to understand underlying mechanisms of ICI response and resistance in mUC. </jats:p>
Authors
Labriola, M; Zhu, J; Gupta, R; McCall, S; Jackson, J; White, JR; Weingartner, E; Kong, E; Simone, P; Papp, E; Gerding, K; Simmons, J; George, DJ; Zhang, T
MLA Citation
Labriola, Matthew, et al. “Characterization of genomic alterations as biomarkers of immune checkpoint inhibitor (ICI) response in metastatic urothelial carcinoma (mUC).Journal of Clinical Oncology, vol. 37, no. 7_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 400–400. Crossref, doi:10.1200/jco.2019.37.7_suppl.400.
URI
https://scholars.duke.edu/individual/pub1416632
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
400
End Page
400
DOI
10.1200/jco.2019.37.7_suppl.400

Concordance between PD-L1 assays for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC).

<jats:p> 577 </jats:p><jats:p> Background: Immune checkpoint inhibitors (ICIs) are now standard of care for mRCC and mUC patients (pts). PD-L1 status is gaining importance as a predictive biomarker, particularly for cisplatin-ineligible mUC. Four different PD-L1 assays vary in thresholds of PD-L1 positivity dependent on tumor type, with limited concordance studies. Given real-world limitations in PD-L1 testing, concordance between assays are needed to distinguish positive (pos)/negative (neg) results and treatment selection. We undertook comparisons of Dako 28–8 and Ventana SP142 assays in mRCC and Dako 22C3 and Ventana SP263 assays in mUC. Methods: 32 patients with mRCC and 18 patients with mUC who had received ICI therapy at Duke Cancer Institute were identified. FFPE archival tumor samples for pts with mRCC were evaluated with Dako 28–8 and Ventana SP142 PD-L1 immunohistochemistry (IHC) assays. For pts with mUC, FFPE archival tumor samples were evaluated with Dako 22C3 and Ventana SP263 PD-L1 IHC assays. Scoring was validated by two pathologists using the scoring system for each assay. PD-L1 status was subsequently correlated to best RECIST response (objective response rate (ORR) defined as stable disease or better)). Results: The majority of mRCC cases (29/32, 91%) were concordant between Dako 28-8 and Ventana SP142 assays (8 cases pos and 21 cases neg), with 3 discordant cases (1 case pos for Dako 28-8 but neg for Ventana SP142 and 2 cases neg for Dako 28-8 but pos for Ventana SP142). The majority of mUC cases (17/18, 94%) were also concordant between Dako 22C3 and Ventana SP263 assays (2 pos cases and 15 neg cases), with 1 indeterminate Dako 22C3 test due to background lymph node. In mRCC, the ORR for PD-L1 pos cases was 45% (5/11) versus 33% (8/24) for PD-L1 neg cases. In mUC, the ORR for PD-L1 positive cases was 50% (1/2) versus 31% (5/16) for PD-L1 neg cases. Conclusions: There was strong concordance between PD-L1 tumor/immune cell assays chosen for comparison in both mRCC and mUC with similar performance characteristics. Although PD-L1 positivity enriches for response to ICIs, many patients respond who are PD-L1 negative. PD-L1 status could be used interchangeably for the majority of cases when selecting treatment in mRCC and mUC. </jats:p>
Authors
Zhu, J; Labriola, M; Cheris, S; Liu, X; Perkinson, K; Su, Z; McCall, S; Huang, J; Gupta, R; Armstrong, AJ; George, DJ; Zhang, T
MLA Citation
Zhu, Jason, et al. “Concordance between PD-L1 assays for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC).Journal of Clinical Oncology, vol. 37, no. 7_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 577–577. Crossref, doi:10.1200/jco.2019.37.7_suppl.577.
URI
https://scholars.duke.edu/individual/pub1416785
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
577
End Page
577
DOI
10.1200/jco.2019.37.7_suppl.577

Research Areas:

Ampulla of Vater
Apoptosis
Bevacizumab
Bile Ducts
Biological Markers
Biopsy
Biopsy, Needle
Cell Differentiation
Cell Line
Cell Nucleus
Cell Proliferation
Cell Survival
Cells, Cultured
Colorectal Neoplasms
Colorectal Neoplasms, Hereditary Nonpolyposis
Cytochrome P-450 CYP2E1
Endocytosis
Epithelial Cells
Epithelial-Mesenchymal Transition
Gene Deletion
Gene Expression Profiling
Gene Expression Regulation
Gene Expression Regulation, Developmental
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
Hedgehog Proteins
Homeodomain Proteins
Humans
Hydroxyproline
Immunohistochemistry
Kruppel-Like Transcription Factors
Lasers
Mesenchymal Stromal Cells
Mesoderm
Microdissection
Mutation
Nuclear Proteins
Oligonucleotides, Antisense
Oligoribonucleotides, Antisense
Oncogenes
Organoplatinum Compounds
Pancreaticoduodenectomy
Pancreatitis
Pilot Projects
Prognosis
Protein Isoforms
Proteome
Proto-Oncogene Proteins
Proto-Oncogene Proteins B-raf
Pyrimidines
RNA, Messenger
Receptors, Cell Surface
Recombinant Proteins
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Stromal Cells
Thiazoles
Tissue Donors
Tumor Markers, Biological
Tumor Necrosis Factor-alpha
Wnt Proteins
Xenograft Model Antitumor Assays
ras Proteins