Anthony Magliocco

• BSc MD FRCPC FCAP
• CEO at Protean BioDiagnostics Inc

Women diagnosed with early-stage breast cancer can develop metastatic disease following successful initial treatment, with bone being the most common site of metastases. The Breast to Bone (B2B) cohort study of early-stage breast cancer patients was established as a research platform to study the basic biology of breast cancer to bone metastasis an...

Introduction: Synthetically lethal mutations offer unique molecular targets for oncologic therapy. At scale, synthetic lethality (SL) is observed when alterations to one gene alone do not correspond with worse overall survival (OS), but simultaneous expression with another gene does correspond with worse OS. Mutually exclusive gene expression is no...

Introduction Breast cancer (BC) is one of the most common cancers affecting the female population in the United States, particularly among the Hispanic community. According to the CDC, the incidence rate of new breast cancer cases in Hispanic women is 95.6 per 100,000 annually, and the mortality rate is 13.7 per 100,000 women annually. Texas is hom...

Next-generation sequencing (NGS) assays play a pivotal role in illuminating the genomic landscape of cancer by providing insights into gene regulation and biomarker detection for the purpose of guiding therapeutic decisions to advance personalized medicine. We validated the Aventa FusionPlus Test, a Laboratory-Developed Test (LDT) that integrates H...

Urothelial bladder cancer (UBC) affects the epithelial cells of the urinary tract and is the most common type of bladder cancer worldwide. Statistically, males are four times more likely to develop UBC than females. It is known that decreased expression of the KDM6A gene, coded on the X chromosome, corresponds with a higher incidence of UBC. KDM6A...

In this retrospective study, we examined the incidence and prevalence of HER2, P53, and P16INK4A protein accumulation patterns in patients diagnosed with rare ovarian cancer. The population-based study included a total of thirteen patients diagnosed at the Saskatoon Cancer Centre during the years 1983-1995. Immunohistochemistry for evaluation of HE...

Variant annotation is an important step in deciphering the functional impact of genomic variants and their association with diseases. In this study, we analyzed 80 pan-cancer cases that underwent comprehensive genomic testing and compared the auto-classified variant tiers among four globally-available software solutions for variant interpretation f...

e18713 Background: It has been well recognized that the rapid advances in precision oncology have not fully been translated into improved access for community cancer programs in the USA, where as much as 95% of oncological assessment and treatment occurs. To address this growing gap, Protean BioDiagnostics and Roche Information Solutions have creat...

The human Lymphocyte antigen-6 (LY6) gene family has recently gained interest for its possible role in tumor progression. We have carried out in silico analyses of all known LY6 gene expression and amplification in different cancers using TNMplot and cBioportal. We also have analyzed patient survival by Kaplan-Meier plotter after mining the TCGA da...

Background/aim: Grading pancreatic neuroendocrine neoplasms (PNENs) via mitotic rate and Ki-67 index score is complicated by interobserver variability. Differentially expressed miRNAs (DEMs) are useful for predicting tumour progression and may be useful for grading. Patients and methods: Twelve PNENs were selected. Four patients had grade (G) 1...

Introduction: Triple-negative breast cancer (TNBC) is an aggressive disease that lacks well-defined molecular targets. It accounts for 15-20% of all breast cancers and disproportionately affects women of color due to both limited access to treatment and genetic variation. Recent studies identified BRCA1(or 2) and the PIK3CA/AKT1/PTEN axis as target...

Importance Bladder-preserving trimodality therapy can be an effective alternative to radical cystectomy for treatment of muscle-invasive bladder cancer (MIBC), but biomarkers are needed to guide optimal patient selection. The DNA repair protein MRE11 is a candidate response biomarker that has not been validated in prospective cohorts using standard...

Background: Ewing sarcoma (ES) can be confirmed by identifying the EWSR1-FLI1 fusion transcript. This study is to investigate whether immunostaining (IHC) of PRKCB—a protein directly regulated by EWSR1-FLI1 is a surrogate maker for diagnosing ES in routine practice. Methods: Microarray gene expression analyses were conducted. RKCB IHC was applied t...

Introduction: Although the risk of colorectal cancer is roughly equal between sexes (slightly higher in males), the molecular profile between the two varies significantly. Many genes identified have a distinctive effect on outcome between these two subgroups, including actionable genes, the most frequently altered genes, and the most significantly...

In this retrospective study, Erb-B2 expression was assessed in 106 patients using Paraffin-Embedded Tissue (PET) to determine the prognostic value in Epithelial Ovarian Carcinoma (EOC) patients diagnosed at Saskatoon Cancer Center between the years 1983-1995. Relationship between Erb-B2 positivity and patient tumor characteristics was assessed for...

This study aimed to determine whether EfficientNet-B0 was able to classify EGFR mutation subtypes with H&E stained whole slide images of lung and lymph node tissue. Background: Non-small cell lung cancer (NSCLC) accounts for the majority of all lung adenocarcinomas, with estimates that up to a third of such cases have a mutation in their epidermal...

5597 Background: Among women with endometrial cancer (EC), African American or Black (AAoB) population share a disproportionate burden of cancer deaths. Previous research exploring genetic and molecular explanations revealed White (W) women with EC are more likely to have mutations in PTEN, while AAoB women have higher rates of mutations in p53. Ho...

The human Ly-6 (hLy-6) gene family has recently gained interest for its possible role in tumor progression. High expression of hLy-6 genes is associated with poor overall survival in pancreatic ductal adenocarcinoma patients. To expand upon this work, we have carried out in silico analyses of all known hLy-6 gene expression in other cancers using T...

Esophageal adenocarcinoma (EAC) surfaces from a dysplastic progression of Barrett's esophagus (BE), with 8% of patients with BE developing EAC; however, there is no current model that directly predicts the risk of progression from image tiles from biopsy slides. Herein, we designed an end-to-end model stratification model to predict BE progression...

Introduction: Despite having a lower incidence of breast cancer, African American (AA) women suffer disproportionately worse outcomes; with more aggressive cancer and higher mortality rates, as well as higher incidence of triple negative breast cancer (TNBC). The cause of these disparities is unclear, but may be driven by different biologic and mol...

Introduction: Triple negative breast cancer (TNBC), defined by the absence of expression of estrogen receptor (ER), progesterone receptor, and HER2, is a heterogenous subgroup of breast cancer which currently accounts for a significant proportion of the mortality from the disease. Consequently, there is an urgent need to identify more effective the...

Background Progression of Barrett esophagus (BE) to esophageal adenocarcinoma occurs among a minority of BE patients. To date, BE behavior cannot be predicted on the basis of histologic features.AimsWe compared BE samples that did not develop dysplasia or carcinoma upon follow-up of ≥ 7 years (BE nonprogressed [BEN]) with BE samples that developed...

The clinical importance of metastatic spread of cancer has been recognized for centuries, and melanoma has loomed large in historical descriptions of metastases, as well as the numerous mechanistic theories espoused. The “fatal black tumor” described by Hippocrates in 5000 BC that was later termed “melanose” by Rene Laennec in 1804 was recognized t...

Introduction: African American (AA) women have a lower incidence of breast cancer (BC), however experience higher rates of more aggressive subtypes, mortality, and worse outcomes compared to Caucasian (C) women. Data also points to disparities among treatment access and response in AA women. Most existing genetic research and clinical trials have b...

HPV infection results in changes in host gene methylation which, in turn, are thought to contribute to the neoplastic progression of HPV-associated cancers. The objective of this study was to identify joint and disease-specific genome-wide methylation changes in anal and cervical cancer as well as changes in high-grade pre-neoplastic lesions. Forma...

Background Previous studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate the relationship of RCB with long-term prognosis across different phenotypic subtypes of breast cancer, to a...

Loss of stromal caveolin-1 (Cav-1) is a biomarker of a cancer-associated fibroblast (CAF) phenotype and is related to progression, metastasis, and poor outcomes in several cancers. The objective of this study was to evaluate the clinical significance of Cav-1 expression in invasive epithelial ovarian cancer (OvCa). Epithelial and stromal Cav-1 expr...

The high lethality of ovarian cancer in the United States and associated complexities of the patient journey across the cancer care continuum warrant an assessment of current practices and barriers to quality care in the United States. The objectives of this study were to identify and assess key components in the provision of high‐quality care deli...

Endometriosis, polycystic ovary syndrome (PCOS) and uterine fibroids have been proposed as endometrial cancer risk factors; however, disentangling their relationships with endometrial cancer is complicated due to shared risk factors and comorbidities. Using genome-wide association study (GWAS) data, we explored the relationships between these non-c...

Loss of stromal caveolin-1 (Cav-1) is a biomarker of a cancer-associated fibroblast (CAF) phenotype and is related to progression, metastasis, and poor outcomes in several cancers. The objective of this study was to evaluate the clinical significance of Cav-1 expression in invasive epithelial ovarian cancer (OvCa). Epithelial and stromal Cav-1 expr...

Background/aim: Muscle invasive bladder cancer (MIBC) is an aggressive disease with high rates of local recurrence following radical cystectomy (RC). Currently, there are no clinically validated biomarkers to predict local only recurrence (LOR) and guide adjuvant treatment decisions. This pilot study evaluated the role of Ki-67, MRE11 and PD-L1 as...

Objectives The Association of Community Cancer Centers (ACCC) launched an initiative to improve care for patients with ovarian cancer (OVCA) in the United States. The project was designed to identify areas of greatest need for quality improvement (QI) initiatives aimed at improving OVCA care. Methods A needs assessment survey and workshop applicat...

Introduction: OncoSignal test was developed to determine and quantify functional signal transduction pathway activity levels of 4 key oncogenic signaling pathways (ER, AR, PI3K and MAPK), based on the quantitative measurement of mRNA expression levels of the direct target genes. Here we present data of a 4 pathway qPCR test, that can be used in ext...

Background: Primary breast cancer is routinely subtyped using immunohistochemistry (IHC) staining and treatment choice is guided by the subtype. Targeted treatment requires the targeted signaling pathway to be active and tumor driving. IHC staining does not provide reliable information on active signaling pathways, and we reported before that clini...

We describe the clinical validation of a targeted DNA and RNA-based next-generation sequencing (NGS) assay at two clinical molecular diagnostic laboratories. This assay employs simultaneous DNA and RNA analysis of all coding exons to detect small variants (single-nucleotide variants, insertions, and deletions) in 148 genes, amplifications in 59 gen...

Background Muscle invasive bladder (MIBC) cancer is an aggressive disease with high rates of local recurrence following radical cystectomy (RC). Currently, there are no clinically validated biomarkers to predict local only recurrence (LOR) and guide adjuvant treatment decisions. This pilot study evaluated the role of Ki-67, MRE11 and PD-L1 as predi...

PURPOSE BRAF V600E mutations are rarely associated with objective responses to the BRAF inhibitor vemurafenib in patients with metastatic colorectal cancer (CRC). Blockade of BRAF V600E by vemurafenib causes feedback upregulation of EGFR, whose signaling activities can be impeded by cetuximab. METHODS One hundred six patients with BRAF V600E -muta...

BACKGROUND Approx. 5% of melanoma pts develop LMD. There are essentially no models of LMD available for therapeutic development. A significant barrier to the development of effective therapies against LMD has been the inability to culture and expand LMD cells. Here we report our strategies to in vitro & in vivo culturing of CSF-CTCs. As a proof of...

The most frequent genetic alterations across multiple human cancers are mutations in TP53 and the activation of the PI3K/AKT pathway, two events crucial for cancer progression. Mutations in TP53 lead to the inhibition of the tumour and metastasis suppressor TAp63, a p53 family member. By performing a mouse-human cross species analysis between the T...

PURPOSE ERBB2 amplification (human epidermal growth factor receptor 2 positivity [HER2 ⁺ ]) in metastatic colorectal cancer (mCRC) has important therapeutic implications that necessitate the need for accurate diagnostics. The study purpose was to establish and validate harmonized diagnostic criteria for HER2 ⁺ mCRC among 3 groups (GI-SCREEN-Japan,...

The incidence of penile squamous cell carcinoma (PSCC) has increased in developed countries over the past decades owing to increased human papilloma virus (HPV) exposure. Despite successful surgical treatment of locoregional PSCC, effective treatment options for advanced disease are limited. The prognosis of patients with bulky nodal and metastatic...

p>A retrospective study of a subset of ovarian cancer cases was evaluated to assess the role of microsatellite instability (MSI) and ploidy status. P53 function is important in the regulation of genomic stability and its expression was examined by immuno-histochemical staining. Genomic instability is also considered a possible indicator of immuno-t...

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two‐sample Mendelian rando...

Importance Pathologic complete response (pCR) is a known prognostic biomarker for long-term outcomes. The I-SPY2 trial evaluated if the strength of this clinical association persists in the context of a phase 2 neoadjuvant platform trial. Objective To evaluate the association of pCR with event-free survival (EFS) and pCR with distant recurrence–fr...

Background: Five-year survival for pancreatic cancer remains low at 8%. While pancreatic cancer health disparities exist among different racial groups, these disparities have not been well investigated in the State of Florida. We aimed to investigate these disparities and hypothesized that cancer cachexia may play a role. Methods: A retrospective r...

Background: Neo-adjuvant chemotherapy (NaCT) facilitates complete surgical resection in locally advanced breast cancer. Due to its association with improved outcome, complete pathologic response (pCR) to neo-adjuvant treatment has been accepted as a surrogate for long-term outcome in clinical trials of human epidermal growth factor receptor 2 (HER...

PURPOSE RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non–small-cell lung cancer (NSCLC). METHODS The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of o...

Triple-negative breast cancer (TNBC) has few therapeutic targets, making nonspecific chemotherapy the main treatment. Therapies enhancing cancer cell sensitivity to cytotoxic agents could significantly improve patient outcomes. A BCL2-associated agonist of cell death (BAD) pathway gene expression signature (BPGES) was derived using principal compon...

BACKGROUND Approx. 5% of melanoma pts develop LMDz. There are essentially no models of LMDz available for therapeutic development. Here we report, the in-vitro & in-vivo culturing of CSF-CTCs. METHODS CSF-CTCs were detected by the Veridex CellSearch® System. Cell-free DNA and cell-associated DNA were extracted, sequenced and profiled. Expanded ex-...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BACKGROUND: Approximately 5% of melanoma pts develop LMDz. There are essentially no models of LMDz available for therapeutic development. Here we report, the in-vitro & in-vivo culturing of CSF-CTCs. METHODS: CSF-CTCs were detected by the Veridex CellSearch® System. Cell-free DNA and cell-associated DNA were extracted, sequenced and profiled. Expan...

PURPOSE Previous studies have shown EndoPredict (EPclin), a test that integrates 12-gene expression data with nodal status and tumor size, to be predictive for risk of distant recurrence in women with estrogen receptor–positive, human epidermal growth factor receptor 2–negative early-stage breast cancer. Here, we modeled expected absolute chemother...

Background/aim: To report a case of mixed medullary/mucinous adenocarcinoma with unusual mutational gene profile. Patients and methods: A 79-year-old female was diagnosed with a colorectal carcinoma of the transverse colon. The diagnostic work-up of this case included thorough clinicopathological evaluation, immunohistochemistry and next generat...

Background: It is well established that alterations of epidermal growth factor receptor (EGFR) are associated with the development and progression of epithelial tumors across several cancer types. Alternative splicing and alterations of EGFR splice sites can cause translational changes and EGFR alterations have historically demonstrated association...

Background: It is well established that alterations of epidermal growth factor receptor (EGFR) are associated with the development and progression of epithelial tumors across several cancer types. Alternative splicing and alterations of EGFR splice sites can cause translational changes and EGFR alterations have historically demonstrated association...

e14746 Background: Next Generation Sequencing based assays are designed to detect genomic aberrations in a limited number of target regions. However, there is a need for accurate measurement of tumor mutational burden (TMB) as low as 4 to as high as 50. As TMB assessment is added to various targeted panels, consistent results between panels are req...

Understanding the intrinsic mediators that render CD8⁺ T cells dysfunctional in the tumor microenvironment is a requirement to develop more effective cancer immunotherapies. Here, we report that C/EBP homologous protein (Chop), a downstream sensor of severe endoplasmic reticulum (ER) stress, is a major negative regulator of the effector function of...

471 Background: Novel targeted therapies are an unmet need in mBC. Androgen receptor (AR) is a rational target in BC and we conducted a phase 1/1b trial assessing safety and tolerability of AR antonist, enzalutamide (ENZ) in combination with gemcitabine and cisplatin (GC) in mBC. Methods: The dose escalation phase allowed patients with mBC regardle...

Background: Patients achieving a pathologic complete response (pCR) following neoadjuvant therapy have significantly improved event-free survival relative to those who do not; and pCR is an FDA-accepted endpoint to support accelerated approval of novel agents/combinations in the neoadjuvant treatment of high risk early stage breast cancer. Previous...

BACKGROUND Approximately 5% of melanoma-associated brain metastasis also develops universally fatal LMDz. The aim of this study was to improve diagnosis and personalized treatment for melanoma-LMDz by enumerating CTCs from CSF. METHODS CSF-CTCs were enriched and detected by Veridex CellSearch® System and the circulating melanoma cell kit. Cell-fre...

Resistance to Androgen receptor (AR) antagonists is a significant problem in the treatment of Castration resistant prostate cancers (CRPCs). Identification of the mechanisms by which CRPCs evade Androgen Deprivation Therapies (ADT) is critical to develop novel therapeutics. We uncovered that CRPCs rely on BRD4-HOXB13 epigenetic reprogramming for an...

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new geno...

Endometrial cancer is the most commonly diagnosed cancer of the female reproductive tract in developed countries. Through genome-wide association studies (GWAS), we have previously identified eight risk loci for endometrial cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer cases and 108,979 controls (including new geno...

Background: Esophageal adenocarcinoma (EAC) is an aggressive malignancy with an increasing incidence in the US. Progression of Barrett's Esophagus (BE) to EAC occurs via a stepwise process, and consequently periodic esophageal biopsies are utilized in order to monitor patients with BE. While a small percent of BE patients will progress to dysplasia...

p>Approximately 5% of melanoma patients develop leptomeningeal disease (LMDz), a highly symptomatic complication with a dismal survival of 8-10 weeks. The aim of this study was to determine whether diagnosis and personalized treatment for melanoma-LMDz could be improved by assessing patient-derived cerebrospinal fluid (CSF) specimens. Circulating t...

In the recent years, wide targeted gene panels have gained popularity, due to their ability to interrogate many genes at the same time. In cancer, particularly, there is a set of ~600 genes known as Cancer Gene Census for which mutations have been causally implicated. Many of the wide cancer panels, therefore, target a subset of these genes. As tar...

Background Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection. Methods Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospective trials (MGH pilot and RTOG 9514) of neoadjuvant/adjuvant MAID chemotherapy and preo...

Table B: clinical and pathologic data for the 51 large, deep, “high-risk” soft tissue sarcoma patients in the TMA study (from RTOG 9514 and the MGH pilot trial).

Table E: the posttreatment (POST) group biomarker expression data.

Figure A: representative AQUA staining for CAIX (a) and GLUT1 (b) in the soft tissue sarcoma tissue microarray specimens.

Table C: follow-up and outcome data for the 51 large, deep, “high-risk” soft tissue sarcoma patients in the TMA study (from RTOG 9514 and the MGH pilot trial).

Table D: the pretreatment (PRE) group biomarker expression data.