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

Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor (ICI) response in metastatic renal cell carcinoma (mRCC).

<jats:p> 63 </jats:p><jats:p> Background: ICIs are now standard of care for mRCC; however, there are few biomarkers to predict ICI response. Recent data from atezolizumab/bevacizumab trials in mRCC suggest tumors with high T<jats:sub>eff</jats:sub><jats:sup>high</jats:sup>/PD-L1+ are more likely to respond to ICI. Here, we use this T<jats:sub>eff</jats:sub> gene panel as well as other markers of inflammation in the tumor microenvironment to correlate with ICI responses. Methods: This multicenter study evaluated 69 pts with mRCC treated with ICIs. FFPE tumor samples were evaluated by RNA sequencing to measure transcript levels of genes related T<jats:sub>eff</jats:sub> status. T<jats:sub>eff</jats:sub> status was defined as the mRNA expression of 17 genes (CD8, CD27, IFNG, GZMA, GZMB, PRF1, EOMES, CXCL9, CXCL10, CXCL11, CD274, CTLA4, FOXP3, TIGIT, IDO1, PSMB9, TAP1), with T<jats:sub>eff</jats:sub><jats:sup>high/low</jats:sup> separated at the median. PD-L1 positivity was defined as ≥1% TPS based on Dako 22C3 IHC assay, and TMB high as &gt; 10 mutations per megabase. Inflamed tumors were defined as CD8 expression in the top 75th percentile compared to a large reference population of multiple tumor types. Best responses to ICI was determined by an expert radiologist using RECIST 1.1 criteria. Inflamed tumor status, T<jats:sub>eff</jats:sub> gene expression, PD-L1 positive, and TMB were associated with disease control (DC, defined as CR, PR, or stable disease). DC comparisons were tested using a chi-squared test with Yates’s continuity correction. Results: DC was 63% (5/8) amongst PD-L1 positive pts and 52% (31/60) in PD-L1 negative patients (p = 0.84). Only 2 pts were TMB high. The majority of mRCC tumors (97%, 67/69) were TMB low. 6-month DC in TMB high tumors was 50% (1/2) and 49.3% (33/67) in TMB low tumors (p = 1.0). 36 pts were classified as T<jats:sub>eff</jats:sub><jats:sup>high</jats:sup> and 33 patients were classified as T<jats:sub>eff</jats:sub><jats:sup>low</jats:sup>. 6-month DC was 61% (22/36) in the T<jats:sub>eff</jats:sub><jats:sup>high</jats:sup> cohort and 36% (12/33) in the T<jats:sub>eff</jats:sub><jats:sup>low</jats:sup> cohort (p = 0.069). 6-month DC was 64% of inflamed tumors (16/25) vs 41% of non-inflamed tumors (18/44) (p = 0.111). Conclusions: TMB high and PD-L1 expression do not reliably predict for DC in pts with mRCC. Utilizing a gene signature score may better predict ICI response. </jats:p>
Authors
Zhu, J; Pabla, S; Labriola, M; Gupta, RT; McCall, S; George, DJ; Dressman, D; Glenn, ST; Nesline, M; George, S; Morrison, C; Zhang, T
MLA Citation
Zhu, Jason, et al. “Evaluation of tumor microenvironment and biomarkers of immune checkpoint inhibitor (ICI) response in metastatic renal cell carcinoma (mRCC).Journal of Clinical Oncology, vol. 37, no. 8_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 63–63. Crossref, doi:10.1200/jco.2019.37.8_suppl.63.
URI
https://scholars.duke.edu/individual/pub1416790
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
63
End Page
63
DOI
10.1200/jco.2019.37.8_suppl.63

Characterization of tumor mutational burden (TMB), PD-L1, and DNA repair genes to assess correlation with immune checkpoint inhibitors (ICIs) response in metastatic renal cell carcinoma (mRCC).

<jats:p> 589 </jats:p><jats:p> Background: ICIs have revolutionized treatment for mRCC; however there are limited predictive biomarkers for response to ICIs. PD-L1 status is still controversial demonstrating little predictive utility in mRCC. TMB is predictive for response to ICIs in melanoma and non-small cell lung cancer (NSCLC), but has not been validated in mRCC. Here, we assess the correlations between TMB and PD-L1 status with outcomes to ICI treatment in mRCC. Methods: 34 patients (pts) with mRCC who had previously received ICI therapy at Duke Cancer Institute were identified. Tumor samples were retrospectively evaluated using a Personal Genome Diagnostics Assay for somatic variants across &gt; 500 genes, as well as TMB and microsatellite status. Tumor samples were also analyzed with the Dako 28-8 PD-L1 IHC assay. Deidentified clinical information was extracted from the medical record and tumor response was evaluated based on RECIST criteria. Results: Pts were grouped by overall response following ICI therapy into either progressive disease (“PD”, n = 18) or disease control group (“DC”, n = 16), defined as either stable disease, partial response, or complete response. Pts displayed a TMB range from 0.36 to 12.24 mutations/Mb with a mean score of 2.83 muts/Mb, with no significant difference between the PD and DC groups (mean 3.01 muts/Mb vs. 2.63 muts/Mb, p &gt; 0.05). 9 of 32 evaluable samples were PD-L1 positive, with 4 in the PD group and 5 in the DC group. Notably, the DC group displayed a significant enrichment of mutations in genes affiliated with DNA repair (including BRCA1, BRCA2, FANCA, FANCB, FANCG, FANCM, MSH3, MSH6, RAD50, RAD51C, RAD51D, RAD54B, RECQL4, and SLX4; p = 0.0444). Conclusions: Overall, in this mRCC cohort, neither TMB nor PD-L1 correlated with patient outcomes or with ICI response. Furthermore, high TMB was not significantly associated with PD-L1 expression within the samples. The higher frequency of mutations in DNA repair genes in the DC group suggests potential use as a predictive signature for ICI response, warranting future prospective studies. </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 tumor mutational burden (TMB), PD-L1, and DNA repair genes to assess correlation with immune checkpoint inhibitors (ICIs) response in metastatic renal cell carcinoma (mRCC).Journal of Clinical Oncology, vol. 37, no. 7_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 589–589. Crossref, doi:10.1200/jco.2019.37.7_suppl.589.
URI
https://scholars.duke.edu/individual/pub1416631
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
589
End Page
589
DOI
10.1200/jco.2019.37.7_suppl.589

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