Medical Specialties Commons^™

Recurrent Carotid Paragangliomas In A Syndromic Patient With A Heterozygous Missense Variant In Dna Methyltransferase 3 Alpha, Ryan J German, Blake Vuocolo, Liesbeth Vossaert, Lisa Saba, Robin Fletcher, Matthew L Tedder, Bekim Sadikovic, Jennifer Kerkhof, Michael Wangler, Carlos A Bacino

Duncan NRI Faculty and Staff Publications

We report a 40-year-old African American female with a novel variant in exon 8 of DNA methyltransferase 3 alpha (DNMT3A), (NM_022552.4: c.905G>C, p.G302A) who presented with a history of recurrent carotid paragangliomas, mediastinal mass, intellectual disability, dysarthria, cholelithiasis, diabetes mellitus, hypertension, and dysmorphic features. We interpret this novel variant as likely pathogenic and causative for the patient's syndromic features of Heyn-Sproul-Jackson syndrome. Heyn-Sproul-Jackson syndrome is a condition caused by gain-of-function genetic changes in DNMT3A. Paragangliomas have also been observed in non-syndromic patients with genetic alterations in DNMT3A. We describe a patient with clinical features of Heyn-Sproul-Jackson syndrome such as …

Investigating The Role Of Rps3 In The Homologous Recombination Dna Repair Pathway, Jerome Robert Dorsey

Theses and Dissertations

Ribosomal proteins have been demonstrated to perform extra-ribosomal functions beyond protein synthesis, including roles in cell signaling, transcription regulation, apoptosis, and DNA repair. Ribosomal protein S3 (RPS3), in particular, has been implicated in DNA repair and apoptosis pathways, suggesting a critical role in maintaining genomic stability. However, the specific mechanisms involving RPS3 are still unknown, particularly in the context of double-stranded break (DSB) repair. DSBs are among the most severe types of DNA damage, often resulting in chromosomal instability or cell death if not properly repaired. Nonhomologous End Joining (NHEJ) and Homologous Recombination (HR) are the two primary DNA repair …

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D' Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: von Hippel-Lindau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C …

Generating Real-World Evidence In Early Alzheimer's Disease: Considerations For Applying The Target Trial Emulation Framework To Study The Safety Of Anti-Amyloid Therapies, Xiaojuan Li, Sonal Singh, Bahareh Rasouli, Jennifer Lyons, Noelle M. Cocoros, Richard Platt, Ivan Abi-Elias, Jerry H. Gurwitz

Department of Medicine Faculty Publications

Anti-amyloid beta monoclonal antibodies (anti-Aβ mAbs) have received approval from the US Food and Drug Administration for the treatment of patients with mild cognitive impairment or mild dementia due to Alzheimer's disease (collectively known as early AD) based on evidence from clinical trials. However, whether findings from these trials are generalizable to the real world is uncertain. We need reliable evidence on the real-world safety of these treatments to inform decision making for clinicians, patients, and caregivers. Using lecanemab as an exemplar, we outline the key considerations in designing and implementing an observational study on safety and utilization outcomes using …

Real-World Interventional Outcomes For Cardiogenic Shock Complicating Acute Myocardial Infarction, John E. Brush Jr., Ann M. Harper, Luke C. Kohan, Zachary Bouker, Kaivalya Dandamudi, Deepak R. Talreja

Department of Medicine Faculty Publications

Acute myocardial infarction with cardiogenic shock (AMICS) carries high mortality and remains a major concern. This concern drives use of interventions with marginal benefit and some evidence of harm. The configuration of hospital care and allocation of interventions for AMICS in our health system created a natural experiment to analyze interventional outcomes for patients with AMICS.

Objective

To compare clinical outcomes among AMICS patients treated with mechanical circulatory support (MCS) using a micro-axial left ventricular assist device and intra-aortic balloon counter-pulsation (IABP).

Design, setting, participants, outcome measures

In this observational study in a large health system, we used clinical registry …

Treatment Of Myocardial Infiltration Of Hodgkins Lymphoma: A Catch-22, Jennifer Priessnitz, Erin Biringen, Fadi Khoury, Christina Bergin

Department of Medicine Faculty Publications

Background: Cardiac sequelae in Hodgkin Lymphoma (HL) can manifest as involvement of the heart and pericardium. Direct cardiac involvement is rare, and myocardial infiltration is distinctly unusual.¹ When it does occur, it is often a late manifestation of lymphoma, with a median onset of 20 months after initial diagnosis, and it is usually associated with advanced-stage disease.²

Case: A 34-year-old male was diagnosed with classic HL by lymph node biopsy. During his hospitalization, the patient remained in sinus tachycardia with heart rate up to 150 with no dysrhythmias. Transthoracic echocardiogram (TTE) revealed a reduced ejection fraction (EF) of 36% concerning …

Emergent Transcatheter Tricuspid Edge-To-Edge Repair For Right Ventricular Shock From Tricuspid Regurgitation In Hypertrophic Cardiomyopathy, Nicholas J. Valle, Amin Yehya, Animesh Rathore, Erich L. Kiehl, Matthew R. Summers

Department of Medicine Faculty Publications

Background

Transcatheter tricuspid edge-to-edge repair (T-TEER) is an emerging technology used to treat severe tricuspid regurgitation (TR). The pivotal trials demonstrating the safety and efficacy of T-TEER exclude patients with severely reduced left ventricular function (≤20%).

Case Summary

We demonstrate the use of T-TEER in a patient with end-stage hypertrophic cardiomyopathy who suffered acute, torrential TR and subsequently developed cardiogenic shock as a complication of high-risk transvenous lead extraction. Why Beyond the Guidelines Currently, there are no guidelines addressing the nonsurgical emergent management of acute TR.

Discussion

The TriClip system (Abbott) may have certain advantages when used in managing acute …

The Timing For Primary Prevention For Icd In The Current Era Of Pharmacotherapy, Anastasia Shchendrygina, Amin Yehya, Hadi Skouri

Department of Medicine Faculty Publications

Recent advances in the pharmacological therapy of heart failure with reduced ejection fraction (HFrEF) have significantly impacted the overall survival, heart failure hospitalisations and rates of sudden cardiac death (SCD). In this context, the relevant timing of placing ICDs as primary prevention is a matter of on-going debate. This manuscript provides evidence for an updated view regarding the timing of implanting ICD in eligible patients with HFrEF receiving optimal guideline-directed medical therapy, accounting for the timing to reverse cardiac remodelling (RCR) occurrence and residual SCD risks over time. Clinically significant RCR occurs beyond 3 months of optimal guideline-directed medical therapy, …

Delayed Hypertension Diagnosis And Its Association With Cardiovascular Treatment And Outcomes, Yuan Lu, John E. Brush Jr, Chungsoo Kim, Yuntian Liu, Xin Xin, Chenxi Huang, Mitsuaki Sawano, Patrick Young, Jacob Mcpadden, Mark Anderson, John S. Burrows, Jordan R. Asher, Harlan M. Krumholz

Department of Medicine Faculty Publications

Importance Hypertension is a major risk factor for cardiovascular disease, yet delays in diagnosis may limit timely treatment initiation and increase cardiovascular risk.

Objectives To examine the timing of clinical hypertension diagnosis, its association with antihypertensive medication prescribing, and its association with long-term cardiovascular outcomes.

Design, Setting, and Participants This retrospective cohort study analyzed electronic health record (EHR) data from an integrated health care system. Adults aged 18 to 85 years with at least 2 outpatient blood pressure (BP) readings of 140/90 mm Hg or more recorded at least 30 days apart from January 1, 2010, to December 31, 2021, …

Balancing Regeneration And Resistance: Targeting Dclk1 To Mitigate Gastrointestinal Radiation Injury And Oncogenesis, Landon L. Moore, Jerry Jaboin, Milton L. Brown, Courtney W. Houchen

Department of Medicine Faculty Publications

Ionizing radiation (IR) poses a dual challenge in medicine; while essential for cancer therapy, it inflicts collateral damage to normal tissues, particularly the gastrointestinal (GI) tract. High-dose IR triggers acute radiation syndrome (ARS), characterized by crypt stem cell depletion, mucosal barrier disruption, inflammation, and potential progression to fibrosis and secondary malignancy. Emerging evidence identifies the epithelial kinase doublecortin-like kinase 1 (DCLK1)—highly expressed in GI tuft cells and cancer stem-like cells—as a master regulator of post-IR responses. DCLK1 integrates DNA repair (via p53/ATM), and survival signaling (via NF-κB, TGF-β, and MAPK) to promote epithelial regeneration, yet these same mechanisms contribute to …

Left Ventricular Assist Device Destination Therapy: A Journey To Home And Beyond, Mian Z. Munir, Marissa C. Galicia-Castillo, Mia Achitoov, Amin Yehya

Department of Medicine Faculty Publications

[Case] Mr H is a 74-year-old man with history of end-stage heart failure (ESHF) secondary to hereditary transthyretin cardiac amyloidosis. Our patient underwent placement of a HeartMate II (Abbott) left ventricular assist device (LVAD) as destination therapy (DT) at an outside hospital and later came to us (Sentara Heart Hospital) for continued management because he resided in the area. Over a 2-year period, the patient experienced multiple hospital admissions for acute heart failure (HF) exacerbations, delirium, and recurrent low-flow alarms. During his last hospitalization, the palliative medicine team was consulted to facilitate goals-of-care discussions with the patient and his family, …

Navigating The Complexities In Gender-Diverse Counseling: Understanding The Interplay Of Gender Identity, Racial Inequities, Economic Marginalization, And Aging, C. Gerwe

Department of Medicine Faculty Publications

Gender-diverse individuals continue to face unique challenges in daily life, with intersecting identities related to race, socioeconomic status (SES), and age further compounding these barriers. These overlapping factors profoundly impact mental health and wellbeing, especially within environments that may lack inclusive or responsive frameworks. Despite increasing awareness, limited guidance exists for counselors on implementing practices that validate intersecting identities while addressing the cumulative effects of marginalization (Canvin et al., 2022). This article synthesizes current research and case examples to illuminate these challenges and offers insights for fostering more inclusive and supportive counseling approaches.

Educational Case: Bullous Pemphigoid, Ryan C. Saal, Alice A. Roberts, Richard M. Conran

Department of Medicine Faculty Publications

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see https://www.academicpathologyjournal.org/pcme.1

Arthroscopic Inlay Biceps Tenodesis Using A Tendon-Docking Anchor, Mark G. Soliman, Katherine S. Worcester M.S., Thomas E. Herron, Kevin F. Bonner

Department of Medicine Faculty Publications

Pathology of the long head of the biceps tendon can be treated surgically with a multitude of tenodesis techniques; however, there is a lack of consensus on which technique provides the most optimal outcomes. Commonly used methods include inlay tenodesis with a bone tunnel and interference screw construct and onlay tenodesis with anchors or unicortical buttons. Although current methods typically provide satisfactory outcomes, many surgeons believe complications and failure rates remain suboptimal across techniques. In this article, we present an arthroscopic suprapectoral biceps tenodesis technique using an anchor device that was developed to address the shortcomings of current techniques, optimize …

Patient-Self Inflicted Lung Injury (P-Sili): An Insight Into The Pathophysiology Of Lung Injury And Management, Himanshu Deshwal, Ahmed Elkhapery, Rudra Ramanathan, Deepak Nair, Isha Singh, Ankur Sinha, Rishik Vashisht, Vikramjit Mukherjee

Department of Medicine Faculty Publications

Acute respiratory distress syndrome (ARDS) is a heterogeneous group of disease entities that are associated with acute hypoxic respiratory failure and significant morbidity and mortality. With a better understanding and phenotyping of lung injury, novel pathophysiologic mechanisms demonstrate the impact of a patient’s excessive spontaneous breathing effort on perpetuating lung injury. Patient self-inflicted lung injury (P-SILI) is a recently identified phenomenon that delves into the impact of spontaneous breathing on respiratory mechanics in patients with lung injury. While the studies are hypothesis-generating and have been demonstrated in animal and human studies, further clinical trials are needed to identify its impact …

The Effect Of Inelastic Compression Wraps On The Quality Of Life Of People With Chronic Venous Insufficiency: A Single-Center, Single-Arm Prospective Study, Abby Hargis Smits, Marita Yaghi, Narges Maskan Bermudez, Hadar Lev-Tov

Department of Medicine Faculty Publications

Background/Objectives: First line therapy for all manifestations of chronic venous insufficiency (CVI) is compression. However, patients frequently report dissatisfaction with compression stockings. Therefore, there is a need to find alternative therapeutic options that can promote compliance. Here, we investigate the impact of the novel, inelastic compression wrap device on quality of life (QoL) in patients with CVI who have failed therapy with compression stockings in the past. Methods: We conducted a six-week, open-label, single-center, non-blinded, prospective cohort study. The primary endpoint was the change in QoL over 6 weeks as measured by the Chronic Venous Disease Quality of Life Questionnaire …

Dance-Related Fractures Occur In The Upper And Lower Extremities At Similar Rates: An Analysis Of The 2004-2023 National Electronic Injury Surveillance System Database, Senah E. Stephens, Joshua F. Edwards, Lisa K. Cannada

Department of Medicine Faculty Publications

Introduction

In the United States, 21% of adolescents participate in dance. Dancers are susceptible to injuries, particularly of the lower extremity, due to extreme positioning, dynamic overload, and repetitive movements.

Objectives

(1) to report the prevalence and describe demographic characteristics of dance-related fractures and (2) to analyze variables associated with disposition status.

Methods

The National Electronic Injury Surveillance System (NEISS) database, published by the US Consumer Product Safety Commission, was used to investigate dance-related fractures diagnosed in a sample of 100 emergency departments over 20 years. Descriptive statistics and demographic variables were analyzed using chi square tests. Age was analyzed …

Effectiveness And Safety Of Intravenous Iron Therapy In Outpatient Obstetrical Clinic For Treatment Of Iron-Deficiency Anemia During Pregnancy, Ellen M. Murrin, Olivia S. Lebeau, Lillian Singer, Mark A. Kassab, Peyton Kalan, Julie Costanzo, Scott A. Sullivan, George L. Maxwell, George R. Saade, Antonio F. Saad

Department of Obstetrics & Gynecology Faculty Publications

Background

Iron-deficiency anemia (IDA) affects over one-third of pregnant patients globally, contributing to severe maternal morbidity and adverse neonatal outcomes. Oral iron supplementation, while cost-effective, is limited by poor absorption, significant gastrointestinal side effects, and poor adherence. The use of intravenous (IV) iron addresses many of these concerns, including eliminating GI side effects and the need for daily therapy. However, administration of IV iron in pregnant patients is typically restricted to specialized infusion centers or hospitals due to concerns about acute side effects, cost, resource utilization, the need for fetal heart rate monitoring, and extended infusion times.

Methods

This descriptive …

Protocol For Development And Validation Of An Early Intervention Device And Its Influence Using Structured Early Physiotherapy (Preemiestep) Intervention On Neuromotor Development In Preterm Infants, Indira D. B. Naidu Boddapati, Sivakumar Gopalakrishnan, Sonia Khurana, Jayashree Purkayastha, Bhaskar Bhatt, Bhamini Krishna Rao

Rehabilitation Sciences Faculty Publications

Early physiotherapy interventions for Moderate to Late Preterm (MLP) infants often lack continuity of care from hospital to home settings. This research aims to develop an Early Intervention (EI) device for home program and determine its influence using STructured Early Physiotherapy (Preemie STEP) intervention in MLP infants. For phase I, qualitative interviews will be conducted with healthcare professionals and parents, to understand user needs on developed prototype. Based on identified needs, an EI device will be developed using a human-centered design approach and iterative design process. In phase II, usability and validity of EI device will be …

Functional Outcome Of Radial Head Replacement And Lateral Ulnar Collateral Ligament (Lucl) Repair In Terrible Triad Injuries Of The Elbow: Can Associated Type I Coronoid Fractures Be Neglected?, Ansarul Haq Lone, Azad Ahmad Shah, Nadeem Ali, Imtiyaz Hussain Dar

Digital Journal of Clinical Medicine

Introduction: Type III coronoid fractures associated with terrible triad injuries of the elbow joint should always be stabilized. However, management of type I and type II fractures is debatable. In this study, we evaluate the functional outcome of neglecting type I coronoid fractures associated with terrible triad injury.

Methods: This prospective study was conducted on 20 patients with a type I coronoid fracture in terrible triad fracture dislocations of the elbow. All the patients were managed by radial head replacement and repair of the lateral collateral ligament without any fixation of the coronoid fracture. All the patients were evaluated clinically …

Havana Syndrome: A Scientific Review Of An Unresolved Medical Mystery, Aishik Dutta

Digital Journal of Clinical Medicine

Background

Since 2016, U.S. and Canadian officials have reported Anomalous Health Incidents (AHIs), or "Havana Syndrome," characterised by a strange sensory experience followed by chronic neurological, cognitive, and vestibular issues. The cause is intensely debated, with primary hypotheses pointing to either psychosocial factors or a directed-energy weapon, creating a significant medical and geopolitical puzzle.

Methods

This review critically assesses the current evidence by analysing peer-reviewed clinical studies and major institutional reports.

Results

The findings are deeply contradictory. A 2020 NASEM report identified directed, pulsed radiofrequency energy as the most plausible mechanism for a core set of symptoms. Conversely, comprehensive 2024 …

Whipple’S Procedure Under Combined Segmental Spinal And Epidural Anesthesia With Enhanced Recovery: A Case Report, Abhirami Ravindran, Imran Ahmed Khan, Naresh Wamanrao Paliwal

Digital Journal of Clinical Medicine

The Whipple’s procedure (pancreaticoduodenectomy), is a complex surgery performed for various indications, usually under general anesthesia (GA). However, GA carries a significant perioperative risk, especially in patients with comorbidities. Combined segmental spinal and epidural anesthesia (CSSE) with low doses of local anesthetics and adjuvants may be a feasible alternative owing to hemodynamic stability, potentially reducing complications and promoting enhanced recovery.

We present a 43-year-old male with periampullary adenoma with high-grade dysplasia who underwent a Whipple’s procedure under CSSE due to high-risk features (e.g., severe jaundice, low blood pressure, and anemia) and chronic smoking and alcoholism. Thoracic epidural (T7–T8) and spinal …

Self-Inflicted, Non-Sexual, Non-Masturbatory Penile Fracture Case Report - An Atypical Presentation, Sajan Sehgal, Vijayakumar R, Sachin Dharwadkar, Amruthraj G. Gowda

Digital Journal of Clinical Medicine

Background: Traumatic injuries to the genitalia are uncommon due to the mobility of the penis and scrotum. Penile fracture is a relatively rare condition arising from disruption of tunica albuginea with rupture of the corpus cavernosum. In order to ensure that such an injury is not missed, it is necessary to have a high index of suspicion to diagnose this condition.

Result: Patient underwent an emergency repair of penile fracture.

Conclusion: We hereby, report a rare case of accidental, non-masturbatory, self-inflicted penile fracture which was diagnosed promptly based on clinical assessment, confirmed radiologically and managed surgically, resulting …

Case Series On Consultation-Liaison Psychiatry In Pain Abdomen With School Refusal Among Children, Jatin Kumar, Aditya Takiar, Kishor M, Sudhamshu K.C, Anil Kumar M.G., Prashanth S.N

Digital Journal of Clinical Medicine

Chronic abdominal pain is one of the most common causes of school refusal in children often leading to multiple hospital visits and expenses. This study was done to assess the psychiatric morbidity underlying functional gastrointestinal complaints in children presenting to paediatric surgery unit. We conducted a prospective case series (N=11; ages 8–13) of children referred from Paediatric Surgery between June and December 2025. All these children presented with idiopathic abdominal pain and a significant period of absence from school. These children were evaluated for any organic causes through the use of various investigations including imaging studies and were referred to …

Evaluating The Efficacy Of Vertical Integration In Training Undergraduate Medical Students Under Competency Based Medical Education Curriculum, Pratham Mehta, Yashika Sharma, Kishor M, Arun M

Digital Journal of Clinical Medicine

Background: The National Medical Council in the Indian Medical Graduate guidelines to enhance learning, recommends Vertical and Horizontal Integration. Vertical integration may be defined as a curricular strategy that aligns para-clinical and clinical teaching across time with a view to enhancing relevance and application of knowledge. The present study is an attempt to test whether vertical integration of Forensic Medicine and Psychiatry is associated with greater short-term learning gains and improved student perceptions compared with conventional didactic lectures.

Methods: With Institutional and Ethics Committee clearance, a two-phase quasi-experimental study was performed across two consecutive academic cohorts (Phase 1, …

Oral Microbiome And Inflammatory Bowel Disease: New Understanding And Call To Action, Michael Saadeh, Sydney Donohue, Shaina Ailawadi, Gordon Hong, David A. Johnson

Department of Medicine Faculty Publications

The oral microbiome is the second largest microbial community in the human body after the gut microbiome. It includes an array of fungi, bacteria, amoebae, flagellates, archaea, and viruses, all of which are potential pathogens. This microbiome can act as a facilitator not only for protection but also for aggravation when dysbiosis occurs. Although conventional thought is this is primarily in terms of oral health issues, such as dental caries and gingival disease. The systemic effects of the oral microbiome however, are relevant to both gastrointestinal (GI) disease and non-GI disease. These systemic risks occur for several reasons, including upregulation …

Association Between Neighborhood-Level Social Vulnerability And Hypertension Outcomes, John E. Brush Jr., Chungsoo Kim, Yuntian Liu, Xin Xin, Chenxi Huang, Iris J. Lundy, Jordan R. Asher, Mitsuaki Sawano, Patrick Young, Jacob Mcpadden, Mark Anderson, John S. Burrows, Harlan M. Krumholz, Yuan Lu

Department of Medicine Faculty Publications

Background

Neighborhood-level social vulnerability is associated with hypertension prevalence and severity and with cardiovascular complications in conditions other than hypertension, but its association with cardiovascular complications in patients with hypertension is understudied.

Objectives

The aim of the study was to examine how the neighborhood-level social vulnerability index (SVI) influences cardiovascular outcomes in a large, diverse cohort of patients with hypertension.

Methods

We used electronic health data to examine the association between census tract-level rankings for the SVI with a composite endpoint of incident myocardial infarction, congestive heart failure, or stroke.

Results

In a longitudinal cohort of 330,972 patients with hypertension …

Percutaneous Levoatrial Cardinal Vein Closure For Stroke Prevention, Chee Spencer, Amir Hasani, Alexander Ellis, David Adler

Department of Medicine Faculty Publications

We report 2 cases of cerebral embolism related to congenital levoatrial cardinal vein anomalies. Both patients had positive echocardiographic agitated saline studies but intact interatrial septum on transesophageal echocardiography. Levoatrial cardinal vein was diagnosed using computed tomography angiography. A novel technique for percutaneous levoatrial cardinal vein closure using vascular plug devices was successful in both patients.

A Linear Presentation Of Cutaneous Rosai Dorfman Disease, Emily Sheetz, Ryan C. Saal, Molly K. Smith, Rachel Chikowski Byrd

Department of Medicine Faculty Publications

[Case description] A 53-year-old female with type II diabetes and hypertension presented to the dermatology clinic with a 3-month history of an asymptomatic linear eruption along the right knee that extended distally along the shin. Initial biopsy showed an atypical lymphohistiocytic infiltrate (Fig 1), which was found to be polyclonal. At her 3-month follow up visit, the eruption demonstrated significant clinical progression with numerous indurated papules and papulonodules, some of which were tender, along the right knee and pretibial surface (Fig 2). No improvement was noted with topical triamcinolone prescribed at her initial visit.

Her2 Alterations Across Solid Tumors: Implications For Comprehensive Testing, Ahmed Ismail, Chimay Jani, Nusrat Jahan, Malla Midhun, Arnab Basu, Garima Gupta, Bassel El-Rayes, Sejong Bae, Tyler Mattox, Cyntanna Hawkins, Rebecca C. Arend, Mehmet Akce, Yanis Boumber, Aakash Desai

Department of Medicine Faculty Publications

Purpose

ERBB2 (HER2) alterations (e.g., overexpression, amplification, and mutations) are known to drive tumor progression. These changes, particularly in non-breast and gastric/gastroesophageal cancers, remain poorly characterized. With pan-tumor approval of HER2-targeted therapies like Trastuzumab deruxetecan (T-DXd), understanding ERBB2 alterations across diverse cancers is crucial.

Methods

HER2 analysis was conducted on 653 solid tumor specimens at the University of Alabama, using immunohistochemistry (IHC), copy number (CN) variation (CNV) assessment, and mutational profiling. The correlation between CN amplification and IHC expression was evaluated using Somers' D ordinal association.

Results

Of the 653 cases, HER2 IHC scores were distributed as 3 + (3.1%), …