Platform presentations will take place on Monday, July 9, 1015–1215. Two rooms will run simultaneous 15 minute presentations during this time and attendees are welcome to switch rooms between individual presentations.

 

Platform Presentations Session A

 

1015-1030

O101 Urinary miRNA analysis to identify biomarkers of aggressive behaviour in early-stage renal cell carcinoma

Ashley Di Meoa,b,c, Michael AS Jewettd, Antonio Finellid, Eleftherios P. Diamandisb,c, George M. Yousefa,b.

aThe Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON.
bDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON.
cThe Advanced Centre for Detection of Cancer at the Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, ON.
dDivision of Urologic Oncology, Princess Margaret Cancer Centre, Toronto, ON.

Objective: To determine whether a limited miRNA signature could accurately distinguish between progressive and non-progressive clear cell renal cell carcinoma small renal masses (ccRCC-SRMs).

Methods: We performed an initial global screen of 754 urinary miRNAs by qRT-PCR in patients with progressive and non-progressive clear cell RCC-SRMs. Twenty-four miRNAs were validated by qRT-PCR. Survival analysis was performed using an independent set of samples from The Cancer Genome Atlas.

Data and Results: Univariate analysis identified miR-328 as the top performing miRNA. miR-328 was significantly down-regulated in progressive (2.97-fold change, p= 0.037), and showed significant discriminatory ability (AUC: 0.68, 95% CI: 0.52, 0.84, p= 0.037). We validated our results in an independent dataset of 195 early stage ccRCC patients (T1a and T1b) from The Cancer Genome Atlas (TCGA). Patients with elevated miR-328 expressing ccRCC tumors had significantly higher overall survival (p = 0.016) compared to patients with lower miR-328 expression. Furthermore, patients with elevated miR-328 expression had significantly higher disease-free survival (p= 0.028) compared to patients with lower miR-328 expression. Common cancer pathways predicted to be targeted by identified miRNAs, include the MAPK (p= 3.0 x10-15) and PI3K-Akt (p= 9.0×10-6) signaling pathways. In addition, previously linked to RCC were identified, including the insulin signaling pathway (p= 3.5×10-7) and VEGF signaling pathway (p<0.0001).

Conclusions: Taken together, dysregulated miRNAs represent potential prognostic biomarkers able to distinguish between progressive and non-progressive early-stage renal lesions. Moreover, using bioinformatics analysis, we identified many pathways targeted by candidate miRNAs.

Keywords: qRT-PCR, miRNAs, small renal masses, renal cell carcinoma

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1030-1045

O102 nCounter technology copy number variation analysis for the classification, diagnosis and predictive prognosis of diffuse gliomas compared to fish

Joy Adekanmbi1,2, Karl Narvacan1, Frank van Landeghem1,2, Iyare Izevbaye1,2.

1University of Alberta.
2Alberta Health Services.

We hypothesize that the novel ncounter technology in the analysis of ATRX, IDH, EGFR, PTEN, MGMT and 1p/19q codeletions using copy number variation has the same sensitivity and specificity as compared with FISH which is the current gold standard.

With the development of this novel nCounter technique for clinical use, the study aims to determine whether nCounter technology can be a robust replacement for FISH in the genetic classification of brain tumours, leading to a cheaper and efficient yet accurate measurement of CNVs as diagnostic, prognostic and predictive oncological markers. Ultimately, the diagnostic efficiency in laboratory analysis gained from this research work aims to improve the overall quality of health care approach in brain tumour oncology.

This may not only be a cheaper option but would also decrease the turnaround time.

Method: This is a retrospective study using FFPE tissue.

  1. Fluorescence in-situ Hybridization was performed as follows
    • 1p and 19q co-deletion: 40 patients
    • EGFR amplification: 32 patients
  2. CNV Elements XT Assay
    • nCounter Assays was used to detect determine copy number variation (CNV) and performed counts of genetic loci in enriched DNA.

Results So Far:

Table 1. Summary of diagnostic parameters for nCounter CNV analysis as compared to FISH

Method

1p deletion

19q deletion

EGFR amplification

Sensitivity (%)

100

100

75

Specificity (%)

42.1

50

100

Positive Predictive Value (%)

45

44.4

100

Negative Predictive Value (%)

100

100

93.8

Likelihood Ratio (+)

1.73

2.00

n/a

Likelihood Ratio (-)

0

0

n/a

ROC curve Pending

Conclusion: Co-deletion of 1p/19q chromosomal arms typically indicate tumors of oligodendroglial origin and generally better prognosis and chemosensitivity (Boots-Sprenger et al.). On the other hand, EGFR amplification is supportive of a diagnosis of glioblastoma multiforme (GBM) or high grade astrocytoma, and predicts a poorer prognosis (Smith et al.). Having a robust and reliable method in detecting the molecular genetics behind brain tumors aids in the diagnosis and prognosis for each neuro-oncological patient.

References: Boots-Sprenger, Sandra H E et al. “Significance of Complete 1p/19q Co-Deletion, IDH1 Mutation and MGMT Promoter Methylation in Gliomas: Use with Caution..” Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 26.7 (2013): 922–929. Web.
Smith, J S et al. “PTEN Mutation, EGFR Amplification, and Outcome in Patients with Anaplastic Astrocytoma and Glioblastoma Multiforme.” JNCI Journal of the National Cancer Institute 93.16 (2001): 1246–1256. Web.

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1045-1100

O103 Desmoplastic stroma in Pancreatic cancer and its delineation using second harmonic generation (SHG) microscopy

Prashant Bavi1#, Joan Miguel Romero1#, Gun Ho2; Amy Jang2, Stefano Serra1, Julie Wilson2, Steven Gallinger1,2.

1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
2PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
#Both authors contributed equally to this work.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized with dense stroma often comprising 90% of tumor volume. Second harmonic generation (SHG) microscopy detects natural collagen on unstained FFPE sections and objectively measures collagen alignment, length, and width. Recent literature supports the notion that tumor initiation and progression may be influenced by changes in collagen structure and organization.

Methods: SHG microscopy was performed on a tissue microarray cohort(TMA) of 165 PDAC patients with detailed clinical information and cancer genomics data. TMAs were custom designed to capture distinct spatial tumor regions rich in dense stroma, high immune infiltrates and cellular tumor. Using CT-FIRE(http://loci.wisc.edu/software/ctfire), a free open-source collagen analysis program, we quantified width, length, straightness and alignment. For validation, TMAs were stained using Masson trichrome, Picrosirius Red and aSMA IHC. Similarly, immune contexture characterization included image analysis of PD-L1, IDO1, CD3+, CD8+, CD68+ and CD206+. We correlated stromal topology with clinical, pathological, genomic and transcriptomic data.

Results: The median alignment, length, width, and straightness measurements were 0.2323 (1 being most aligned), 60.95, 6.0806, 0.9196 (1 being perfectly linear), respectively. Simple linear regression analysis showed direct association of SHG fibre width and Masson’s trichrome (p<0.0001; R-squared 0.20). SHG fibre straightness showed a weak correlation with CD3 and CD8 TILs. Both SHG fibre median alignment(p=0.0248) and median length(p=0.0096) was significantly higher in the Immunogenic and squamous subgroups as compared to Progenitor and ADEX subgroups (Baileys classification).

– click here for figure

Conclusion: This study validates SHG as an imaging modality for PDAC for assessment of collagen topology. Therefore, SHG may serve as a potential biomarker to help characterize PDAC stroma and eventually stratify patients for better clinical trial design in both conventional and immune targeted therapies.

Keywords: Pancreatic cancer, Second harmonic generation (SHG) microscopy, Imaging, Fibrosis, immune contexture, RNA seq, whole genome sequencing.

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1100-1115

O104 Integrated Molecular Analysis of Papillary Renal Cell Carcinoma and Precursor Lesions Unfolds an Evolutionary Biological Process From Kidney Progenitor Cells

Rola M Saleeba,b, Mina Faraga, Qiang Dinga, Michelle Downesb,c, Georg Bjarnasond, Fadi Brimoe, Pamela Planta, Fabio Rotondoa, Zsuzsanna Lichnera, George M Yousefa,b.

aDepartment of Pathology and Laboratory Medicine, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON.
bDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON.
cDepartment of Pathology, Sunnybrook Health Sciences Centre, Toronto, ON.
dDepartment of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, ON.
eDepartment of Pathology, McGill University Health Center, Montreal, QC.

Objective: Papillary renal cell carcinoma (PRCC) is common in end stage kidney disease (ESKD). They are known to have multiple distinct subtypes. Papillary adenomas (PAs) are small benign papillary lesions that are thought to be PRCC precursors and are also very prevalent in ESKD. The evolution of PAs to PRCCs and their relationship to ESKD are poorly understood.

Methods: A total of 135 cases of PAs, normal kidneys, ESKD and PRCCs were collected. Molecular analysis of the different groups was performed using miRNA expression, Copy number variations (CNV), and whole exome sequencing (WES). Stem cell markers BCL2, CK7, LGR5 were assessed using immunohistochemical image analysis.

Data and Results: Molecular analysis showed similarities between ESKD and PA. Renal tubular progenitor cell markers were significantly increased in ESKD (p <0.0001) and PAs (p= 0.02) in comparison to the normal kidney. Embryonic developmental pathways were enriched in PA and all the PRCC subtypes. Lysine methyltransferase2C (KMT2C) was found to have a common frameshift insertion among all papillary lesions. Pathway analysis showed an evolutionary interconnected model from ESKD as a first stage to the different PRCC tumor subtypes as final stage.

Conclusion: Normal kidney progenitor cells are likely cells of origin of PRCCs that in ESKD, and hence the frequency of PRCCs in ESKD. There are connected molecular events that underlie the transformation of ESKD to PAs to the different PRCC subtypes. The results shed light on novel biological aspects of PRCC development and can aid in clinical management and early prevention of these tumors.

Keywords: Papillary adenoma, end stage kidney disease, Papillary renal cell carcinoma

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1115-1130

O105 Raman microscopy: a diagnostic and prognostic tool for pathologists

Andrée-Anne Grosseta,b, Catherine St-Pierrea,c, Karl St-Arnauda,c, Kelly Aubertina, Michael Jermync,d, Fred Saada,e, Frédéric Leblonda,c, Dominique Trudela,b,f.

aCentre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM), Montreal, QC.
bDepartment of Pathology and Cellular Biology, Université de Montréal, Montreal, QC.
cDepartment of Engineering Physics, Polytechnique Montreal, Montreal, QC.
dThayer School of Engineering, Dartmouth College, Hanover, NH, United States
eDepartment of Surgery, Université de Montréal, Montreal, QC
fDepartment of Pathology, Centre hospitalier de l’Université de Montréal (CHUM), Montreal, QC.

Objective: The integration of complementary analyzes to help pathologists determine the diagnosis and prognosis of cancer patients is important. Raman microscopy is a promising tool, based on the analysis of how light is scattered after reflection on a surface. This non-destructive and label-free technique indicates the molecular content of the tissue. However, current Raman microscopy studies implicate parameters that are incompatible with the clinical workflow, such as frozen tissue, expensive slides and/or 15μm sections of formalin-fixed paraffin-embedded (FFPE) tissues. The objective of this study was to evaluate the potential of Raman microscopy as a clinical tool.

Methods: The rapid standardized clinical protocol for the preparation of FFPE tissues of our hospital (CHUM) and low cost aluminum slides were used. Tissue microarrays containing FFPE prostate tissues from 80 patients were included in this study. A confocal Raman microscope was used for the acquisition of Raman spectra.

Data and Results: A total of 160 Raman spectra from benign prostatic tissues and 320 Raman spectra from prostate cancer were acquired. Prostate tissue classification with artificial intelligence, specifically with Support Vector Machine (SVM) technique, identified benign tissue, cancer, grade groups and biochemical recurrence within 18 months with accuracy, sensitivity and specificity greater than 83%.

Conclusions: This is the first study demonstrating the potential of Raman microscopy using a rapid standardized clinical protocol for the preparation of FFPE tissues. The evaluation of the diagnosis and prognosis of patients by this technique should be exploited by pathologists for precise patient management.

Keywords: diagnosis, prognosis, Raman microscopy, prostate cancer

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1130-1145

O106 Genetic determinants of palbociclib efficacy

Boris Virine1,2,3, Michael V. Roes1,2, James I. MacDonald1,2, Fred A. Dick1,2,3,4.

1London Regional Cancer Program, Western University, London, ON.
2Department of Biochemistry, Western University, London, ON.
3Schulich School of Medicine, Western University, London, ON.
4Child Health Research Institute, Western University, London, ON.

Introduction: Palbociclib is a member of a new class of targeted cancer therapies, recently approved for the treatment of breast cancer. It inhibits the CDK 4/6 proteins, whose deregulated expression drives tumor cell proliferation. While clinical trials have shown promising results, targeted therapeutic agents such as Palbociclib are known to have a high proportion of non-responders amongst patients. Using a CRISPR-Cas9 library screen, we sought to identify genes involved in cell-cycle regulation that can act as potential screening targets for Palbociclib-sensitive tumors.

Methods: We treated a population of MDA-MB-435 cells with lentivirus carrying the TKO-V3 CRISPR library and then selected for Palbociclib resistant cells for 28 days. Genomic DNA was isolated from treatment and control group cells, used for PCR amplification of sgRNA encoding sequences and products were sequenced using Illumina chemistry. Results were analyzed with MAGeCK and BAGEL screen analytics software.

Results: Guide RNA targeting RB1, a tumor suppressor gene deactivated by CDK4/6, was the most abundant sequence in the Palbociclib treated population relative to the control. Other genetic targets whose abundance increased following the Palbociclib-screen are active in growth or transcription regulation. This group included a variety of genes, some of which have a known link to the CDK4/6 pathway while for others the relationship remains uncharacterized.

Conclusion: We have identified a subset of cell cycle regulatory genes whose activity may sensitize cancer cells to Palbociclib activity. Further elucidation of these genes can identify molecular markers for the screening of patients likely to be responsive to Palbociclib therapy.

Keywords: Targeted therapy, Breast cancer, CRISPR, Cell cycle, RB1

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1145-1200

O107 Degree of PTEN loss in index prostate cancer nodules independently predicts risk of treatment failure

Tamara Jamaspishvilia,b, Palak Patela,b, Rachel Liverganta,b, Yi Niue,f, Yingwei P. Pengc,d,e, David M. Bermana,b.

aCancer Biology & Genetics Division, Queen’s Cancer Research Institute, Kingston, ON.
bDepartment of Pathology and Molecular Medicine, Queen’s University, Kingston, ON.
cDepartment of Public Health Sciences, Queen’s University, Kingston, ON.
dDepartment of Mathematics and Statistics, Queen’s University, Kingston, ON.
eDivision of Cancer Care and Epidemiology, Queen’s Cancer Research Institute, Kingston, ON.
fSchool of Mathematical Sciences, Dalian University of Technology, Dalian, Liaoning, China.

Objective: To study prognostic significance and spatial heterogeneity of ERG and PTEN status in early prostate cancer.

Methods: The study included 272 low and intermediate risk prostate cancer patients who underwent radical prostatectomy (RP) from 2000 to 2012 at Kingston General Hospital. All cases were represented on a tissue microarray. When present, analysis included both high and low grade cancer components from index and secondary tumour lesions.

Data and Results: Consistent with previous studies, any PTEN loss (partial or complete) was significantly associated with biochemical recurrence (BCR) (p<0.0001), pathological stage (p=0.011) and Gleason score (p=0.004). Patients with both PTEN loss and strong ERG positivity had the shorter recurrence-free survival (p=0.007). PTEN loss was more frequent in index nodules (n=47, 96% vs n=7, 14%) and had higher risk of recurrence (HR=2.74, p=0.00034) compared to cases with PTEN loss only in secondary tumor nodules (HR=1.47, p=0.59), whereas ERG expression was almost equally distributed between index and non-index tumor foci (60% vs 40%). The extent of PTEN loss was significantly associated with the risk of recurrent disease (HR=1.245, p=0.00036). ERG did not show prognostic significance with respect to tumor grade (p=0.052), pathological stage (p=0.126) or treatment failure (p=0.184).

Conclusions: PTEN is a powerful prognostic biomarker for low and intermediate risk prostate cancers. PTEN loss may identify driver/primary tumor nodules and this observation should be considered during biopsy. Extent of PTEN loss appears to have paramount importance on disease progression.

Keywords: prostate cancer, PTEN, ERG, heterogeneity, prognosis

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1200-1215

O108 Altered VJ junctions of immunoglobulin light chains in rheumatoid arthritis patients

Lina Chena, Gillian Wub.

aDepartment of Pathology and Molecular Medicine, Queen’s University, Kingston, ON.
bDepartment of Kinesiology and Health Science, York University, Toronto, ON.

Objective: Rheumatoid arthritis (RA) is an autoimmune disease that attacks synovial joints with autoantibodies. Studies suggested that the processes of immunoglobulin (Ig) gene recombination, somatic hypermutation and subsequent selection are altered in RA patients resulting in the detrimental autoantibodies.

Methods: IgK and IgL expressed sequence tags from synovial tissue of RA and healthy controls (HC) in Megablast database were identified using Nucleotide Blast and submitted to IMGT/V-QUEST human Ig for junction analysis.

Data and Results: 49 IgK and 26 IgL sequences from RA, and 197 IgK and 188 IgL sequences from HC were identified. For IgK, J subtype (p<0.0001) but not V subtype usage was different between RA and HC. RA had more deletions (p<0.0001), additions (p=0.001), reading frameshift (RFS, p=0.001), total (p=0.04) and missense (p=0.01) mutations, and acidic or basic residues (p=0.0004) than HC in IgK. For IgL, both V (p<0.0001) and J (p=0.0002) subtype usage were different between RA and HC. There was no difference in deletion, addition, and total or missense mutations between RA and HC in IgL. 52% HC and 27% RA IgL sequences had RFS (p=0.003), and RA also had lower pI (p=0.002) and more acidic residues (p=0.0001) than HC.

Conclusion: The results provided evidence that addition and deletion causing reading frame shift, somatic hypermutations, and V or J subtypes usage difference led to amino acid composition change in the VJ junction of Ig light chains in RA. This may have an impact on the antibody-antigen binding affinity and could be the cause of autoimmunity.

Keywords: rheumatoid arthritis, immunoglobulin light chain, VJ recombination, somatic hypermutation

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Platform Presentations Session B

 

1015-1030

O201 MyPathologyReport.ca: an online pathology education resource for patients

Anthea J. Lafrenierea, Bibianna M. Purginaa, Diponkar Banerjeea, Jason K. Wassermanb.

aDepartment of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON.
bDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON.

Introduction: Patients are receiving increasing access to their electronic medical record (EMR) and laboratory results, including pathology reports, are amongst the most frequently accessed pieces of information. MyPathologyReport.ca is a novel website exclusively providing pathology education to patients, designed to help patients understand the language of pathology and to effectively navigate their pathology report. Feedback on this free online tool was solicited from healthcare providers to determine whether MyPathologyReport.ca would serve the needs of their patient population.

Methods: An online questionnaire was distributed to targeted healthcare providers at the Ottawa Hospital, the Children’s Hospital of Eastern Ontario, and select community practices. Respondents were required to navigate MyPathologyReport.ca and complete a 15-question survey regarding their use of pathology reports and whether MyPathologyReport.ca provided useful information for their patients.

Results: There were 22 respondents across six specialties, including multiple surgical subspecialties, pediatrics, medical genetics, and family medicine. Over 80% reported that all features of MyPathologyReport.ca were either very useful or extremely useful, including: i) how to read a pathology report; ii) an illustrated pathology dictionary; and iii) articles outlining the most common pathological diagnoses. 72% of respondents stated they were somewhat likely or very likely to recommend MyPathologyReport.ca to a patient.

Conclusion: An informed patient is an active member of the healthcare team. Our feedback questionnaire demonstrates that clinicians find MyPathologyReport.ca to be a useful patient resource. Next steps involve longitudinal assessment of MyPathologyReport.ca from non-medical community members and evaluation of patient satisfaction and knowledge with access to this resource.

Keywords: website, online, patient education

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1030-1045

O202 Knowledge translation: the bumpy ride from bench to bedside

Sarah Morgan1, George M. Yousef1,2.

1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON.
2Department of Laboratory Medicine and Molecular Diagnostics, St Michael’s Hospital, Toronto, ON.

Objective: Knowledge translation (KT) aims to close the gaps between knowledge and practice. KT is a dynamic process of mobilizing best-practice evidence to guide decisions in healthcare. Despite the significant advancement in genetics/genomics techniques, there is still a noticeable gap in integrating genetics into patient care. We aimed at systematically reviewing the literature to identify the challenges in implementation of KT and define the roadmap for personalized medicine to improve quality of care.

Method and Results: We searched PubMed using key word combinations for articles published from 2003 to 2017 that met inclusion/exclusion criteria. Using the online search and expert opinion, challenges were identified and a roadmap defined. Major obstacles to implementation of KT included genetic testing, integration of results into patients’ care, and health care system challenges. The first challenge includes limitations of genetic testing, genetic variants of unknown significance, turnaround time, standardization and reproducibility. The second includes lack of proper training of primary care physicians to provide genetic consultation, scientific evidence, and ethics. The last challenge pertains to health care system and comprises lack of access to genetic testing services, EMR integration of genetic results, clinical decision support and clarity of roles.

Conclusions: KT is essential for improving quality of care. Major molecular discoveries are on the rise. Implementation of KT requires developing strategies to enhance awareness and promote behavior change congruent with research evidence, designing a systematic approach by pathologists and stakeholders for interpretation of genetic testing and patient’s centered care.

Keywords: Knowledge translation, precision-personalized medicine

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1045-1100

O203 The use of reflex and reflective testing strategies for early detection of pituitary dysfunction in patients from primary care

Manal Elnenaeia, Derek Minneya, David B. Clarkeb,c, Andrew Kumar-Misira, Syed Ali Imranc.

aDepartment of Pathology and Laboratory Medicine, Nova Scotia Health Authority & Dalhousie University, Halifax, NS.
bDivision of Neurosurgery, Department of Surgery, Dalhousie University, Halifax, NS.
cDivision of Endocrinology, Department of Medicine, Dalhousie University, Halifax, NS.

Objective: Although early detection of pituitary dysfunction reduces morbidity and mortality, mass population screening of these disorders is not feasible. We hypothesized that reflex and reflective testing strategies within the current laboratory system may capture suspicious hormonal test patterns. This may allow early detection of pituitary dysfunction in previously undiagnosed patients.

Methods: An algorithm based upon specific reflex rules was set within the laboratory information system to capture blood tests that may indicate early or subtle pituitary dysfunction. Over a 12-month period, results for all tests reflecting pituitary function were filtered daily using this algorithm. These were analyzed by a laboratory clinician, and further reflective tests ordered where appropriate. If there was biochemical evidence of pituitary dysfunction a comment instigating referral to endocrine or neuropituitary clinics was added to the results. Patients who had a laboratory intervention were followed up to determine the clinical outcome.

Results: 1099 patients were identified by the reflex algorithm. Further tests were added reflectively by a laboratory clinician on 214 patients. Subsequent referrals of 48 patients were made to the endocrine or neuropituitary clinics. Of these, 29 patients were diagnosed with pituitary related conditions (insufficiency and/or adenoma). These results demonstrate that the use of reflex and reflective testing in the clinical chemistry laboratory can aid in the early detection of pituitary dysfunction.

Conclusion: This data supports the use of reflective testing in aiding early detection of pituitary dysfunction.

Keywords: Endocrine; Pituitary; Reflex Testing; Clinical Chemistry

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1100-1115

O204 Geospatial variation and sociodemographic associations with abnormal estimated glomerular filtration rate (eGFR) result rates in Calgary, Alberta

Irene Maa, Maggie Guof, Daniel Muruveb,c, Hallgrimur Benediktssona,f, Christopher Nauglera,d,e,f.

aDepartment of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB.
bDepartment of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB.
cSnyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB.
dDepartment of Family Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB.
eDepartment of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB.
fCalgary Laboratory Services (CLS), Calgary, AB.

Objective: Using secondary laboratory and Census data, geospatial distribution and sociodemographic associations with chronic kidney disease (CKD) was assessed by evaluating estimated glomerular filtration rate (eGFR) testing rates in Calgary, Alberta.

Methods: CLS’ Laboratory Information System was accessed for all adult community patients who received an eGFR test result in 2011. An abnormal eGFR result was defined as eGFR < 60 ml/min/1.73m2. Sociodemographic variables were inferred by combining laboratory data with the 2011 Canadian Census data. Results were mapped to calculate the geospatial distribution of abnormal eGFR testing rates within the city.

Data and Results: In 2011, 8.1% of the 346,663 adult community patients who received an eGFR test had an abnormal result (8.4% female, 7.7% male). Geospatial analysis revealed statistically significant high abnormal eGFR result rate in specific neighbourhoods in the NW, SW and SE quadrants of the city. Some communities in the inner city and in the city limits showed significantly low abnormal eGFR result rates. Women (RR = 1.11), and those ≥ 70 years of age were significantly associated with an increased risk for CKD (P<0.0001), while visible minority Chinese (RR = 0.73, P=0.0011), South Asians (RR = 0.67) and those with a high median household income (RR = 0.88) had a significantly reduced risk for CKD (P<0.0001).

Conclusions: Distinct geospatial variation and at risk sociodemographic groups for abnormal eGFR testing rates were observed in Calgary. Certain sociodemographic groups were at a higher risk for CKD, while others were protective in this analysis.

Keywords: Chronic Kidney Disease (CKD), Estimated Glomerular Filtration Rate (eGFR), Laboratory Medicine, Census Data, Geospatial Mapping

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1115-1130

O205 Standardizing immunohistochemistry critical assay performance controls across a distributed hospital network

Mélina Janellea, Alfred Cuellara, Jason Karamchandania.

aDepartment of Pathology, McGill University, Montreal, QC.

Objective: Consolidation of laboratory activities from multiple hospitals allows for an opportunity to implement evidence-based immunohistochemistry critical assay performance controls (iCAPC) for immunohistochemical (IHC) testing across a distributed hospital network. The goal of this study was to identify the multi-tissue blocks (MTBs) which allow for the greatest number of IHC test to have an on-slide iCAPC.

Methods: We reviewed Nordic immunohistochemical Quality Control (NordiQC) and Canadian Immunohistochemistry Quality Control (cIQc) best practices and identified those IHC assays where there is an evidence-based tissue expression suitable for an on-slide iCAPC to deploy across a multi-site hospital network.

Data and Results: At one large site (~50K tests/year), 46% of the IHC tests offered have an evidence-based iCAPC. Of these tests, 75% are covered by 2 MTBs (A: Liver, Pancreas, Tonsil, Appendix; B: Non-neoplastic breast, Ectocervix, Her2+ Breast cancer). These stains account for 64% of the total volume of IHC ordering, and 87% of IHC testing where there are evidence-based iCAPCs.

Conclusions: Implementing 2 well-designed MTBs allowed us to include an on-slide iCAPC for 87% of tests where there is an evidence-based control to ensure that the technical assay worked as expected. This addition improves the clinical utility of negative result in assays in which properly handled tissue has no internal on-slide control.

Keywords: Immunohistochemistry; Quality Improvement; Laboratory Management

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1130-1145

O206 Developing a pan-Canadian framework for high-quality molecular cancer biomarker testing

Natasha Camusoa, Anubha Prashada, Mary Argent-Katwalaa, John Srigleya.

aCanadian Partnership Against Cancer, Toronto, ON.

Objective: While some standards exist for ensuring high quality molecular biomarker testing, there remains a lack of comprehensive pan-Canadian standards for a wider variety of diagnostic, prognostic and predictive slide-based or liquid molecular tests. To address this gap, the Canadian Partnership Against Cancer has identified recommendations to be included in a framework for high-quality molecular biomarker testing. This is Canada’s first attempt at creating pan-Canadian recommendations to enable robust and consistent use of high-quality cancer biomarker testing across jurisdictions.

Methods: The Canadian Partnership Against Cancer commissioned an environmental scan to identify key areas of focus to improve molecular cancer biomarker testing. A comprehensive literature review was conducted, followed by key informant interviews from across the country to generate a list of recommendations to be included.

Data and Results: Nineteen recommendations under five categories were developed, including 1) General Recommendations, including accreditation, certification and licensing, internal quality control and quality assurance; 2) Pre-analytical Phase, including sample receipt, sample handling and test selections; 3) Analytical Phase, including data analysis and equipment; 4) Post-Analytical Phase, including reporting and timing of results; 5) Additional Areas for Exploration.

Conclusions: The recommendations are intended to minimize variation in quality assurance across biomarker testing, ensure a minimum standard of performance in laboratory testing and ultimately improve the cancer diagnostic process. The recommendations can strengthen quality improvement at national, regional and local health systems’ levels and inform policy and planning, measurement and performance.

Keywords: biomarker testing, pan-Canadian, framework, cancer

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1145-1200

O207 Diagnostic discrepancy rates in anatomic pathology: a 7-year single institution review

Lik Hang Leea, Martin J. Trottera.

aDepartment of Pathology and Laboratory Medicine, Providence Health Care, University of British Columbia, Vancouver, BC.

Objective: Diagnostic discrepancy rates, determined by second review of pathology cases, are usually reported from the perspective of the reviewing institution (e.g. regional cancer centre) or consultation service. External review major discrepancy rates are documented in the literature as 4.6-14.7% (25th-75th percentile).1 We employed a different approach by evaluating, through the lens of the originating pathology department, a single institution diagnostic discrepancy rate for all surgical pathology and cytopathology cases undergoing external second review as part of multidisciplinary cancer care.

Methods: All external second review pathology reports on surgical pathology and cytopathology cases originating from our pathology department and reviewed at the regional cancer centre as part of multidisciplinary team care were evaluated over a 7-year period (2011-2017). The primary case pathologist compared the original report with the review report, categorized the paired reports as – agreement, minor discrepancy (no change in prognosis or clinical care), or major discrepancy (potential change in prognosis or clinical care), and documented explanations for the discrepancy. All major discrepancy explanations were re-evaluated and categorized by the authors (e.g. false positive vs. false negative).

Data and Results: External second review was performed on 7542 cases (3.4% of total workload). Minor discrepancy was identified in 532 cases (7.1%) and major discrepancy was identified in 72 cases (0.95%). Classification of major discrepancies is shown below.

Reason

# of cases

 

Reason

# of cases

False negative

34

 

Primary vs. metastasis

5

Cancer classification

11

 

Grading

3

False positive

10

 

Other

2

Margins

7

 

 

 

The most common false negative discrepancies were missed malignancy (13 cases), under-calling invasive disease (7 cases), and under-diagnosis of lymphoma (sometimes incidental) by the primary sign-out pathologist (5 cases).

Conclusions: Evaluation of targeted (patients with cancer) external second review diagnostic discrepancies by the originating pathology department provides an alternative perspective on the issue of diagnostic error in pathology. Our tertiary-level, university-affiliated pathology department had a major diagnostic discrepancy rate of 0.95% for diagnoses made in patients with cancer undergoing multidisciplinary review.

Keywords: diagnostic discrepancy, diagnostic error, quality assurance, error reduction

1Nakhleh RE, Nosé V, Colasacco C, et al. Arch Pathol Lab Med. 2016;140:29–40

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1200-1215

O208 Influence of specimen characteristics on PD-L1 testing in non-small cell lung cancer: a retrospective study

Andréanne Gagnéa, Emily Wanga, Nathalie Bastienb, Michèle Oraina, Patrice Desmeulesa,b,c, Sylvain Pagéb, Sylvain Trahanb,c, Christian Couturea,b,c, David Joubertd, Philippe Jouberta,b,c.

aResearch Center, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC.
bDepartment of Pathology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, QC.
cLaval University, Molecular biology, medical biochemistry and pathology department, Quebec City, QC.
dUniversity of Ottawa, Department of Criminology, Ottawa, ON.

Introduction: Molecules targeting Programmed death receptor 1 (PD-1) or its ligand (PD-L1) are part of the standard care of patients with advanced non-small cell lung carcinoma (NSCLC). The biomarker for predicting response to treatment is PD-L1 expression by tumor cells using immunohistochemistry. According to guidelines, PD-L1 should not be performed on specimens containing less than 100 tumors cells, older than three years and on cytologic specimens. However, these recommendations are based on limited evidence.

Objective: To evaluate PD-L1 testing results on specimens with non-recommended characteristics.

Methods: This retrospective cohort included 1249 consecutive patients with NSCLC tested for PD-L1 between September 2016 and April 2017 in our department. Clinicopathological data were retrieved from pathology reports. PD-L1 immunostaining was performed using 22C3 antibody and scored as the percentage of tumor cells (TPS) with membranous staining. The associations between specimen characteristics and PD-L1 were evaluated with chi-square test, ANOVA and multinomial logistic regressions.

Results: 35.5% of patients had a specimen with a non-recommended characteristic. In multivariate analyses, specimens with less than 100 tumor cells and older than three years were significantly associated with lower PD-L1 staining (TPS >50% vs <1% OR=0.43, p=0.001 and OR=0.39, p=0.02). There was no association between PD-L1 and cytology when compared to tissue specimens.

Conclusion: Our results suggest that cytologic and tissue specimens are equivalent for PD-L1 testing. However, testing on a specimen with less than 100 tumor cells or older than three years lowers the odds of a positive result. A rebiopsy should be considered to optimize the chances to receive the therapy.

Keywords: PD-L1 staining, quality assurance, non-small cell lung cancer

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