Renal cell carcinoma with fibromyomatous stroma (RCC FMS) and with hemangioblastoma-like areas is part of the RCC FMS spectrum in patients with tuberous sclerosis complex.

Aims: Sporadic renal cell carcinomas with fibromyomatous stroma (RCC FMS) with coexistent haemangioblastoma (HB)-like morphology have been previously reported. Such morphology has not, however, been documented in patients with tuberous sclerosis complex (TSC). We evaluated clinicopathologic, immunohistochemical and molecular findings of RCC FMS with HB-like features in three TSC patients.

Development of a Nomogram to Integrate Molecular Testing and Clinical Variables to Improve Malignancy Risk Assessment Among Cytologically Indeterminate Thyroid Nodules.

The introduction of molecular testing (MT) of cytologically indeterminate thyroid nodules (ITNs) alone has not impacted thyroidectomy rates. Due to this, we evaluated the incremental diagnostic value of various clinical variables in addition to MT results, in predicting the risk of malignancy (ROM) among ITNs. This prospective observational study included 1024 consecutive ITNs that underwent reflexive ThyroSPEC MT between Jul 30, 2020, and Oct 30, 2023.

Real-World Analysis of Post-Progression Treatment Patterns and Outcomes for Mutation-Positive Patients Treated with First-Line Osimertinib.

The use of osimertinib in the first-line (1L) setting is an effective treatment option for sensitizing -mutations (m+) and has significantly altered the standard of care practice for m+ disease in Canada. Unfortunately, acquired resistance to osimertinib is almost universal, and outcomes are disparate. Post-progression treatment patterns and the outcome of real-world Canadian m+ patients receiving 1L osimertinib were the focus of this retrospective review.

Primary cutaneous NUT carcinoma with BRD4::NUTM1 fusion.

Nuclear protein in testis (NUT) carcinoma, molecularly defined by the NUTM1 gene rearrangement, is most commonly reported in young adults in the sinonasal tract, nasopharynx, or thorax. At these sites, NUT carcinoma is an extremely aggressive malignancy with dismal prognosis. Recently, five cases of primary cutaneous NUT adnexal carcinoma have been reported with BRD3 and NSD3 fusion partners.

Prospective Validation of ThyroSPEC Molecular Testing of Indeterminate Thyroid Nodule Cytology Following Diagnostic Pathway Optimization.

Molecular testing for cytologically indeterminate thyroid nodules (ITNs) is often reported with incomplete data on clinical assessment and ultrasound malignancy risk (USMR) stratification. This study aimed to clinically validate the diagnostic accuracy of a novel molecular test, assess the incremental preoperative malignancy risk of other clinical factors, and measure the impacts of introducing molecular testing at the population level. Comprehensive clinical data were collected prospectively for the first 615 consecutive patients with ITNs in a centralized health care system following implementation of a reflexive molecular test.

Consensus Recommendations to Optimize the Detection and Reporting of Gene Fusions by RNA-Based Next-Generation Sequencing.

The detection of gene fusions by RNA-based next-generation sequencing (NGS) is an emerging method in clinical genetic laboratories for oncology biomarker testing to direct targeted therapy selections. A recent Canadian study (CANTRK study) comparing the detection of gene fusions on different NGS assays to determine subjects' eligibility for tyrosine kinase TRK inhibitor therapy identified the need for recommendations for best practices for laboratory testing to optimize RNA-based NGS gene fusion detection. To develop consensus recommendations, representatives from 17 Canadian genetic laboratories participated in working group discussions and the completion of survey questions about RNA-based NGS.

A Subset of Pancreatoblastomas May Arise From an Adenomatous Precursor: An Ampullary Pancreatoblastoma and Adjacent Adenoma With a Shared Molecular Phenotype in an Adult Patient.

Pancreatoblastomas are rare pediatric tumors. In adults, they are exceedingly rare and seem to have a worse prognosis. Most are sporadic, though rare, cases occur in patients with familial adenomatous polyposis.

CANTRK: A Canadian Ring Study to Optimize Detection of NTRK Gene Fusions by Next-Generation RNA Sequencing.

The Canadian NTRK (CANTRK) study is an interlaboratory comparison ring study to optimize testing for neurotrophic receptor tyrosine kinase (NTRK) fusions in Canadian laboratories. Sixteen diagnostic laboratories used next-generation sequencing (NGS) for NTRK1, NTRK2, or NTRK3 fusions. Each laboratory received 12 formalin-fixed, paraffin-embedded tumor samples with unique NTRK fusions and two control non-NTRK fusion samples (one ALK and one ROS1).

The impact of population-based EGFR testing in non-squamous metastatic non-small cell lung cancer in Alberta, Canada.

Objectives: While Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors have been shown to be effective in phase III randomized trials, the value of targeted therapies has been challenging to evaluate at the population-level. We examined the impact of population-level EGFR testing and treatment on survival outcomes among non-squamous metastatic Non-Small Cell Lung Cancer (NSCLC) patients.

Materials And Methods: Real-world, population-level data were collected from all de novo non-squamous metastatic NSCLC patients in Alberta, Canada from 2004 to 2020.

Real-World Management and Outcomes of Crizotinib-Treated ROS1-Rearranged NSCLC: A Retrospective Canadian Cohort.

The use, safety and effectiveness of crizotinib as part of the management of ROS1-rearranged NSCLC patients in a real-world Canadian clinical cohort was the focus of this retrospective review. Twenty-one ROS1-rearranged patients with advanced/metastatic disease receiving crizotinib between 2014-2020 were identified; crizotinib demonstrated tolerability and effectiveness in this population where outcomes were similar to those described in other crizotinib-treated real-world cohorts, but lower than those of the PROFILE 1001 clinical trial population. Systemic anti-cancer therapy prior to crizotinib initiation occurred in half of the study cohort, with platin-pemetrexed and immune checkpoint inhibitors being most common.

Systematic population-based identification of NTRK and RET fusion-positive thyroid cancers.

Objective: The aim of the study was to identify patients with NTRK fusion-positive or RET fusion/mutation-positive thyroid cancers, who could benefit from neurotrophic tyrosine kinase receptor (NTRK) or receptor tyrosine kinase (RET) inhibitors.

Methods: Patients were identified in the Calgary prospective thyroid cancer database (N= 482). Patients were 'pre-screened' with clinically available MassARRAY® BRAF test, Colon Panel, Melanoma Panel, or ThyroSPEC™.

Retrospective Real-World Outcomes for Patients With -Rearranged Lung Cancer Receiving ALK Receptor Tyrosine Kinase Inhibitors.

Introduction: This study explored the use, safety, and efficacy of initial use of an ALK-inhibiting targeted therapy (ALK tyrosine kinase inhibitor [TKI]) in patients with -rearranged NSCLC in a population-based, real-world clinical population within the province of Alberta, Canada.

Methods: Demographic, clinical, treatment, and outcome data of the patients with advanced or metastatic -rearranged NSCLC receiving their first ALK TKI between 2014 and 2019 were included in the analysis.

Results: A total of 92 patients with -rearranged NSCLC treated with ALK TKI (78% crizotinib, 22% alectinib) were identified.

Identification of high-impact gene-drug pairs for pharmacogenetic testing in Alberta, Canada.

Objectives: To facilitate decision-making and priority-setting related to Alberta's Pharmacogenomics (PGx) testing implementation strategy by identifying gene-drug pairs with the highest potential impact on prescribing practices in Alberta.

Patients And Methods: Annual drug dispensing data for Alberta from 2012 to 2016 for 57 medications with PGx-based prescribing guidelines were obtained, along with population estimates and demographics (age and ethnicity). Frequencies of actionable PGx genotypes by ethnicity were obtained from the Pharmacogenomics Knowledgebase (PharmGKB).

Fulminant Bacterial Myocarditis Presenting as Myocardial Infarction.

A previously healthy man presented with inferior myocardial infarction and recent upper respiratory tract infection. Bacteremia was detected and treated; however, the patient developed refractory polymorphic ventricular tachycardia storm and shock. Clinical autopsy revealed the diagnosis of isolated bacterial myocarditis.

Combined loss of TFF3 and PTEN is associated with lethal outcome and overall survival in men with prostate cancer.

Background: Trefoil Factor 3 (TFF3) has been implicated in Prostate Cancer (PCa) progression. However, its prognostic value and association with other biomarkers have not been fully explored. We assessed the combined value of TFF3 and PTEN in two cohorts: one is managed surgically for localized PCa and the second is managed non-surgically by androgen deprivation therapy for advanced disease.

Human pegivirus-1 associated leukoencephalitis: Clinical and molecular features.

Etiologic diagnosis is uncertain in 35% to 50% of patients with encephalitis, despite its substantial global prevalence and disease burden. We report on 2 adult female patients with fatal leukoencephalitis associated with human pegivirus-1 (HPgV-1) brain infection. Neuroimaging showed inflammatory changes in cerebral white matter.

High alpha-methylacyl-CoA racemase (AMACR) is associated with ERG expression and with adverse clinical outcome in patients with localized prostate cancer.

Alpha-methylacyl-CoA racemase (AMACR) is a well-characterized marker extensively utilized in prostate cancer (PCA) diagnosis. However, the prognostic value of AMACR expression and its relation to TMPRSS2-ERG gene rearrangement as one of the most common molecular alterations in PCA is not fully explored. AMACR expression was investigated in a cohort of 218 men with localized PCA treated by radical prostatectomy and correlated with ERG and various clinical and pathological parameters.

AKT loss in human epithelial cells treated with severe hypoxia.

Cancer cells which can survive and or proliferate in hypoxia may be resistant to anti-cancer treatment. In our previous work, we showed that we could group cell lines treated with severe hypoxia into either hypoxia-induced cell cycle arrest-sensitive or resistant phenotypes, and hypoxia-induced cell death (HCD)-sensitive or resistant phenotypes. We showed that the resistant phenotypes were associated with high levels of active-AKT in late hypoxia and sensitive cells were associated with decreased or undetectable levels of AKT in late hypoxia.

Identification and characterization of demethylase JMJD1A as a gene upregulated in the human cellular response to hypoxia.

Hypoxia is commonly found in human solid cancers and serves as a selective environment for the survival of aggressive cancer cells and as protection from anti-cancer therapies. In addition to a shift to anaerobic metabolism, the cellular response to hypoxia includes cessation of cell division and/or cell death. These mechanisms have still not been defined.

Signaling and apoptosis differences between severe hypoxia and desferoxamine treatment of human epithelial cells.

The mechanisms by which cells undergo proliferation arrest or cell death in response to hypoxia are still not completely understood. Originally, we showed that HeLa and Hep3B carcinoma cells undergo different proliferation responses in hypoxia. We now show that these 2 cell lines also have different cell death responses to severe hypoxia, with HeLa showing both cell cycle arrest and apoptosis (as early as 12 h after hypoxia treatment), and Hep3B showing resistance to both.

Cell cycle kinase inhibitor expression and hypoxia-induced cell cycle arrest in human cancer cell lines.

Flow cytometric analysis of fibroblasts, normal breast epithelial cells and breast or other cancer cell lines identified variation in the abilities of cell lines to undergo cell cycle arrest as a response to hypoxia. Human mammary epithelial cells (HMEC), normal fibroblasts (Hs68 and WI38), HeLa cervical carcinoma and HTB-30 breast carcinoma cells arrest in G(1)/S in response to severe hypoxia. Hep3B hepatocellular carcinoma cells did not exhibit orderly G(1)/S arrest in response to severe hypoxia.