Rex C. Bentley's research while affiliated with Duke University and other places
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Publications (193)
Rhabdomyosarcoma (RMS), a cancer characterized by features of skeletal muscle, is the most common soft‐tissue sarcoma of childhood. With 5‐year survival rates among high‐risk groups at <30%, new therapeutics are desperately needed. Previously, using a myoblast‐based model of fusion‐negative RMS (FN‐RMS), we found that expression of the Hippo pathwa...
Background: High-risk human papillomavirus (hrHPV) testing is recommended for primary cervical cancer screening and is used alongside cytology to triage screening abnormalities to colposcopy. Most screening-based hrHPV tests involve pooled detection of any hrHPV type or of HPV 16/18 only. Extended HPV genotyping, particularly of non-16/18 hrHPV typ...
Background:
High-risk human papillomavirus (hrHPV) testing is utilized in primary cervical cancer screening, generally along with cytology, to triage abnormalities to colposcopy. Most screening-based hrHPV testing involves pooled detection of any hrHPV or of HPV16/18. Cervical neoplasia progression risks based on extended hrHPV genotyping-particul...
The BRCA1-associated protein 1 (BAP1) gene encodes a tumor suppressor that functions as a ubiquitin hydrolase involved in DNA damage repair. BAP1 germline mutations are associated with increased risk of multiple solid malignancies, including mesothelioma, uveal melanoma, renal cell carcinoma, and high-grade rhabdoid meningiomas. Here, we describe t...
Context.—:
Pathology reports are the main modality in which results are communicated to other physicians. For various reasons, the diagnosis may be qualified on a spectrum of uncertainty.
Objective.—:
To examine how communication of uncertainty is an unexamined source of possible medical error. No study to our knowledge has examined pathology re...
Background
Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited.
Methods
Women ( n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genot...
Background
Phyllodes tumors are rare fibroepithelial neoplasms that are classified by tiered histopathologic features. While there are protocols for the reporting of cancer specimens, no standardized reporting protocol exists for phyllodes.Methods
We performed an 11-institution contemporary review of phyllodes tumors. Granular histopathologic detai...
The study evaluated morphologic patterns, mutational profiles, and β-catenin immunohistochemistry (IHC) in copy-number low (CNL) endometrial adenocarcinomas (EAs). CNL EAs (n=19) with next-generation or whole genome sequencing results and available tissue for IHC were identified from our institutional database. Clinical data and histologic slides w...
Primary gastrointestinal stromal tumors (GIST) largely occur in the luminal gastro-intestinal tract and are extremely rare in the liver. On a molecular level, a small minority of GISTs are characterized by SDH deficiency. To date, SDH-deficient GISTs have been exclusively reported in the stomach, except a single duodenal primary. Here, we report a...
Objectives
Soft tissue sarcomas are a group of tumors derived from the mesenchymal origin. Historically, they have been classified according to morphologic and immunohistochemical characteristics. The advent of multiplexed next-generation sequencing (NGS), specifically RNA sequencing, has modified the classification of such tumors and others by det...
Malignant ectomesenchymoma (MEM) is a rare multiphenotypic tumor comprised of mesenchymal and neuroectodermal components. MEM is typically diagnosed in infants and younger children and outcomes are variable. The current approach for treating MEM includes targeting the more aggressive mesenchymal component of the tumor, which is often rhabdomyosarco...
A hallmark of alveolar rhabdomyosarcoma (ARMS) is the presence of a chromosomal translocation encoding the PAX3-FOXO1 fusion oncogene (FP-ARMS). Patients presenting with FP-ARMS represent the subset of rhabdomyosarcoma patients with the worst prognosis, and when metastatic, survival for these children and adolescents is less than 10%. Nevertheless,...
Purpose:
Gene-expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation of clinical utility has been hindered by non-standardized methods which are not applicable in a clinical setting. We sough...
Background
Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is approximately four years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for overall survival in HGSO...
A hallmark of fusion-positive alveolar rhabdomyosarcoma (aRMS) is the presence of a chromosomal translocation encoding the PAX3–FOXO1 fusion oncogene. Primary cell-based modeling experiments have shown that PAX3–FOXO1 is necessary, but not sufficient for aRMS tumorigenesis, indicating additional molecular alterations are required to initiate and su...
Objective:
Major changes in the classification of ovarian carcinoma histotypes occurred over the last two decades, resulting in the current 2014 World Health Organization (WHO) diagnostic criteria that recognize five principal histotypes: high-grade serous, low-grade serous, endometrioid, clear cell, and mucinous carcinoma. We assessed the impact...
Squamous cell carcinoma with pseudoangiosarcomatous features is a rare but well-recognized variant of squamous cell carcinoma. These tumors exhibit complex anastomosing channels lined by neoplastic cells, histologically mimicking a vasoformative mesenchymal tumor. Immunohistochemically, the published cases expressed epithelial markers and were cons...
Purpose:
Non-atypical papillomas (NAPs) diagnosed on core needle biopsy (CNB) frequently undergo surgical excision due to highly variable upstaging rates. The purpose of this study is to document our dual-institution upgrade rates of NAPs diagnosed on core needle biopsy and review the upgrade rates reported in the literature.
Materials and method...
Purpose:
Alveolar rhabdomyosarcoma (aRMS) is a childhood soft tissue sarcoma driven by the signature PAX3-FOXO1 (P3F) fusion gene. 5-year survival for aRMS is <50%, with no improvement in over four decades. Although the transcriptional co-activator TAZ is oncogenic in carcinomas, the role of TAZ in sarcomas is poorly understood. The aim of this st...
Background:
Stromal tumor-infiltrating lymphocytes (TILs) might predict pathologic complete response (pCR) in patients with HER2-positive (HER2+) breast cancer treated with trastuzumab (H). Docetaxel (T), carboplatin (C), H, and pertuzumab (P) have immune-modulating effects. Pre- and post-treatment immune biomarkers in cancers treated with neoadju...
The role of host epigenetic mechanisms in the natural history of low-grade cervical intraepithelial neoplasia (CIN1) is not well characterized. We explored differential methylation of imprinted gene regulatory regions as predictors of the risk of CIN1 regression. A total of 164 patients with CIN1 were recruited from 10 Duke University clinics for t...
The American Journal of Gastroenterology is published by Springer Nature on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological...
While improvement in survival for pediatric cancer patients over the last 40 years has been encouraging, certain cancer types evade cure. One such example is fusion-positive alveolar rhabdomyosarcoma (aRMS), a pediatric soft tissue sarcoma of mesenchymal origin with skeletal muscle features and a 5-year survival rate of <50%. A hallmark of this agg...
Ovarian cancer accounts for 5% of cancer deaths and is the fifth leading cause of cancer death in women in the United States. While incidence is higher in European American (EA) than African American (AA) women, five-year survival is worse for AA women (36%) than EA women (44%). Access to appropriate surgery and treatment is a major contributor but...
Some patients with cancer never develop metastasis, and their host response might provide cues for innovative treatment strategies. We previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. CFH prevents complement-mediated cytotoxicity (CDC) by inhibiting formation of cell-lytic memb...
Objective:
Vascular smooth muscle cell (SMC) migration is regulated by cytoskeletal remodeling as well as by certain transient receptor potential (TRP) channels, nonselective cation channels that modulate calcium influx. Proper function of multiple TRP channels requires the scaffolding protein Homer 1, which associates with the actin-binding prote...
Vulvar squamous cell carcinoma is a rare and heterogeneous disease. Young women who develop vulvar squamous cell carcinoma tend to develop non-keratinizing histological types (warty and basaloid squamous cell carcinomas) in the setting of warty and/or basaloid-type usual vulvar intraepithelial neoplasia (uVIN); these tumors are commonly human papil...
Rhabdomyosarcoma (RMS), a cancer characterized by features of skeletal muscle histogenesis, is the most common soft tissue sarcoma of childhood and adolescence. Survival for high-risk groups is less than 30% at 5 years. RMS also occurs during adulthood, with a lower incidence but higher mortality. Recently, mutational profiling has revealed a corre...
Background: Epigenetic mechanisms are hypothesized to be etiologically involved in progression of cervical intraepithelial neoplasia (CIN) to invasive cervical cancer (ICC), although empirical data are lacking.
Methods: A total of 304 women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV w...
We evaluate a new hybrid algorithm for determining nuclear morphology using angle-resolved low coherence interferometry (a/LCI) measurements in ex vivo cervical tissue. The algorithm combines Mie theory based and continuous wavelet transform inverse light scattering analysis. The hybrid algorithm was validated and compared to traditional Mie theory...
Rhabdomyosarcoma is a soft tissue sarcoma associated with the skeletal muscle lineage. Of the two predominant subtypes, known as embryonal (eRMS) and alveolar (aRMS), aRMS has the poorer prognosis, with a 5-year survival rate of <50%. The majority of aRMS tumors express the fusion protein PAX3-FOXO1. As PAX3-FOXO1 has proven chemically intractable,...
Study Objective: To evaluate if the use of Valleylab mode ("V mode") (Covidien, Mansfield, MA) electrothermal energy for colpotomy during total laparoscopic hysterectomy (LH) results in a smaller margin of thermal injury to the upper vagina compared with traditional cut/coagulate (cut/coag) electrothermal energy. Design: Prospective randomized clin...
Purpose
For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at...
Context:
Metastases from ampullary malignancies are common, but spread to the testicle and paratesticular tissue is exceedingly rare with only 2 reported cases in the literature.
Case report:
We report a case of a 70 year-old male with a history of ampullary adenocarcinoma status post pancreaticoduodenectomy who presented with a symptomatic righ...
Objective
To determine whether a minimally invasive approach to hysterectomy is associated with an increased rate of lymph vascular space invasion (LVSI) and/or malignant pelvic peritoneal cytology in endometrial cancer.
Methods
We performed a single institution analysis of 458 women with endometrial cancer who underwent either total abdominal hys...
Objective:
Bacterial colonization of the fetal membranes and its role in pathogenesis of membrane rupture is poorly understood. Prior retrospective work revealed chorion layer thinning in preterm premature rupture of membranes (PPROM) subjects. Our objective was to prospectively examine fetal membrane chorion thinning and to correlate to bacterial...
Alveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle characterized by expression of the paired box 3-forkhead box protein O1 (PAX3-FOXO1) fusion oncogene. Despite its discovery nearly two decades ago, the mechanisms by which PAX3-FOXO1 drives tumor development are not well characterized. Previously, we reported that PAX3-FOX...
We describe clinicopathologic and immunohistochemical features of an unusual case of cystic fibrosis manifesting in the cervix as a mass lesion, mimicking cervical adenocarcinoma. A 24-year-old nulligravida with cystic fibrosis developed heavy postcoital vaginal bleeding 4 months after starting oral contraceptives and was found to have a cervical m...
Background: Differential distributions of oncogenic HPV genotypes among racial/ethnic groups may explain observed disparities in ICC incidence and mortality rates. We describe HPV genotypes associated with CIN1-3 in a multiethnic cohort of women visiting colposcopy clinic following a cervical abnormality.
Methods: We enrolled 516 women attending co...
Background:
Six gene expression subtypes of invasive epithelial ovarian cancer were recently defined using microarrays by Tothill and colleagues. The Cancer Genome Atlas (TCGA) project subsequently replicated these subtypes and identified a signature predictive of survival in high-grade serous (HGS) cancers. We previously validated these signature...
Preterm premature rupture of the membranes (PPROM) is an important etiology of preterm birth and source of significant neonatal morbidity. We propose that PPROM occurs in the setting of long-standing altered tissue remodeling, which creates a vulnerable environment for the fetal membranes and pregnancy. We tested the hypothesis that PPROM is the re...
Rhabdomyosarcoma (RMS) is a malignancy with features of skeletal muscle, and the most common soft tissue sarcoma of childhood. Survival for high-risk groups is approximately 30% at 5 years and there are no durable therapies tailored to its genetic aberrations. During genetic modeling of the common RMS variants, embryonal RMS (eRMS) and alveolar RMS...
In early-stage breast cancer, adjuvant chemotherapy is associated with significant systemic toxicity with only a modest survival benefit. Therefore, there is considerable interest in identifying predictive markers of response to therapy. Doxorubicin, one of the most common drugs used to treat breast cancer, is an anthracycline chemotherapeutic agen...
Struma ovarii exhibiting malignant histology are uncommon, and an aggressive clinical course in the form of initial extraovarian spread or recurrence is even more exceptional for these tumors.
To determine whether specific histologic features have predictive value in distinguishing clinically benign from clinically malignant struma ovarii.
Blinded...
Inactivating somatic mutations in the ARID1A gene are described in a significant fraction of clear cell and endometrioid ovarian cancers leading to loss of the corresponding protein (BAF250a). Expression of BAF250a was examined in clear cell and endometrioid cancers accrued as part of the North Carolina Ovarian Cancer Study, a population-based case...
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and remains refractory to combined-modality therapy in patients with high risk disease. In skeletal myogenesis, Notch signaling prevents muscle differentiation and promotes proliferation of satellite cell progeny. Given its physiologic role in myogenesis and oncogenic role i...
Lung cancers can display immune cell infiltration although the role of an adaptive immune response in disease pathogenesis is unknown. To investigate the possibility of a functional humoral response to the tumor, we surveyed histologic sections from non-small cell lung cancer (NSCLC) tumors for germinal centers (GCs) and assessed whether there was...
We aim to report that skin biopsy, a non-invasive test by neurological standards, may lead to a diagnosis. A 4-year-old male presented with a 2-year history of epilepsy and progressive developmental regression. The patient had a mildly elevated ammonia level; however, evaluation for the accumulation of excess serum amino acids and evaluation of uri...
In a series of 177 breast carcinomas, we found that the Oncotype DX Recurrence Score (RS) was correlated with six pathobiologic features: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status, and the three components of the Nottingham tumor grade. The RS also correlated with a composite index (the Breast Can...
To describe retroperitoneal neural structures at risk during uterosacral ligament suspension and to estimate risk of neural injury based on uterosacral ligament suspension suture placement technique.
Uterosacral ligament suspension was performed in 10 unembalmed female cadavers. In each cadaver, bilateral uterosacral ligament suspension sutures wer...
Bevacizumab is increasingly being tested with neoadjuvant regimens in patients with localized cancer, but its effects on metastasis and survival remain unknown. This study examines the long-term outcome of clinical stage II/III rectal cancer patients treated in a prospective phase II study of bevacizumab with chemoradiation and surgery. As a benchm...
We explored plasma and urinary concentration of four members of the vascular endothelial growth factor (VEGF) family as potential response and toxicity biomarker of bevacizumab with neoadjuvant chemoradiation in patients with localized rectal cancer.
The levels of VEGF, placental growth factor (PlGF) and soluble VEGF receptors 1 and −2 (sVEGFR1 and...
10647 Background: The Oncotype Dx recurrence score (RS) has been widely adopted by oncologists to guide adjuvant chemotherapy in patients with ER-positive breast carcinomas. The majority of genes included in the Oncotype assay are components of the ER/PR and HER2 pathways or reflect proliferative potential, which is correlated with tumor grade. Met...
The natural history of 27 cases of biologically malignant struma ovarii from a series of 88 cases of histologically malignant or histologically proliferative struma ovarii is described. The extraovarian spread was evident at presentation in 17 patients. The malignant nature of the other 10 tumors became apparent only after they recurred. The tumors...
The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is increasingly being tested with pre-operative (neoadjuvant) regimens in patients with localized cancer, but its effects on metastasis and survival remain unknown.
This study examined the outcome of clinical stage II/III rectal cancer patients treated on a prospective phase II...
Description of the 53 genes related to DNA Repair and p53-mediated damage response pathways.
(0.02 MB XLS)
Expanded description of the statistical analytic approach.
(0.12 MB PDF)
Marginal screen results for 484 DNA Repair SNPs in the North Carolina Ovarian Cancer Study.
(0.12 MB XLS)
Functional annotation data for the six SNPs with a MISA Bayes Factor >10.
(0.05 MB XLS)
We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study (NCOCS), a population-based, case-control study.
The analysis was restricted to 364 invasive serous ovarian cancer cases and 761 controls of white, no...
Isolated colonic schwannomas are rare gastrointestinal mesenchymal tumors; only a small number of cases have been reported. The incidence is 2% to 6% of all submucosal tumors of the gastrointestinal tract. They are thought to be distinctive from conventional schwannomas that arise in soft tissue or the central nervous system. Although colonic schwa...
We performed case-control analyses using data from the North Carolina Ovarian Cancer Study to determine risk factors that distinguish primary peritoneal cancer (PPC) from epithelial ovarian cancer (EOC). Our risk factor analyses were restricted to invasive serous cancers including 495 EOC cases, 62 PPC cases and 1,086 control women. Logistic regres...
The aim of this study was to determine if core biopsy-proven benign papillomas of the breast need to be surgically excised.
Mammographic and pathologic database review from January 1994 to January 2004 revealed 178 papillary lesions diagnosed by core biopsy in 176 women (mean age, 59 years). All lesions had >or=24 months of imaging follow-up (n = 7...
To resolve controversial issues regarding vulvar Paget disease through analysis of a substantial number of cases.
The medical records and pathology slides of 56 patients with a diagnosis of vulvar Paget disease were reviewed. Possible correlation between clinical and pathological data was examined.
Most patients were Caucasian and their mean age at...
A long circulating liposomal, nanoscale blood pool agent encapsulating traditional iodinated contrast agent (65 mg I/mL) was used for micro-computed tomography (CT) imaging of rats implanted with R3230AC mammary carcinoma. Three-dimensional vascular architecture of tumors was imaged at 100-micron isotropic resolution. The image data showed good qua...
The Duke experience with 56 vulvar Paget disease patients was analyzed emphasizing pathologic features and controversial issues. Nearly all patients were Caucasian, and their mean age was 69 years. The average length of follow-up was 5.6 years. For each case, the following histologic features were evaluated and their association with disease course...
Clinical studies converge on the observation that circulating cytokines are elevated in most cancer patients by anti-vascular endothelial growth factor (VEGF) therapy. However, the source of these molecules and their relevance in tumor escape remain unknown. We examined the gene expression profiles of cancer cells and tumor-associated macrophages i...
Struma ovarii that display extraovarian spread or later recurrence is exceedingly rare. Among 88 patients with "malignant" struma ovarii followed for prolonged periods, several features helped to predict the adverse clinical course. Adhesions (graded 2 to 4+), peritoneal fluid (> or =1 L) or ovarian serosal rent were worrisome features, occurring i...
To assess the safety and efficacy of neoadjuvant bevacizumab with standard chemoradiotherapy in locally advanced rectal cancer and explore biomarkers for response.
In a phase I/II study, 32 patients received four cycles of therapy consisting of: bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; fluorouracil infusion (225 mg/m(2)/24 hours...
Cervical cancer is the second most common female cancer worldwide. The ability to quantify physiological and morphological changes in the cervix is not only useful in the diagnosis of cervical precancers but also important in aiding the design of cost-effective detection systems for use in developing countries that lack well-established screening a...
Feasibility and reproducibility of microarray biomarkers in clinical settings are doubted because of reliance on fresh frozen tissue. We sought to develop and validate a paradigm of frozen tissue collection from early breast tumors to enable use of microarray in oncology practice. Frozen core needle biopsies (CNBx) were collected from 150 clinical...