Fibronectin Contributes to a BRAF Inhibitor-driven Invasive Phenotype in Thyroid Cancer through EGR1, Which Can Be Blocked by Inhibition of ERK1/2.

Unlabelled: Mutations in BRAF are common in advanced papillary and anaplastic thyroid cancer (PTC and ATC). However, patients with BRAF-mutant PTC currently lack therapies targeting this pathway. Despite the approved combination of BRAF and MEK1/2 inhibition for patients with BRAF-mutant ATC, these patients often progress.

Mutual exclusivity of ESR1 and TP53 mutations in endocrine resistant metastatic breast cancer.

Both TP53 and ESR1 mutations occur frequently in estrogen receptor positive (ER+) metastatic breast cancers (MBC) and their distinct roles in breast cancer tumorigenesis and progression are well appreciated. Recent clinical studies discovered mutual exclusivity between TP53 and ESR1 mutations in metastatic breast cancers; however, mechanisms underlying this intriguing clinical observation remain largely understudied and unknown. Here, we explored the interplay between TP53 and ESR1 mutations using publicly available clinical and experimental data sets.

Lenvatinib Plus Anti-PD-1 Combination Therapy for Advanced Cancers: Defining Mechanisms of Resistance in an Inducible Transgenic Model of Thyroid Cancer.

Combination therapy with lenvatinib plus programmed death-1 (PD-1) immune checkpoint blockades (ICBs) is under investigation in many solid tumors, including thyroid cancer. Lenvatinib is known to reduce angiogenesis and may overturn the immunosuppressive effects of vascular endothelial growth factor in the tumor microenvironment. Previous studies investigating the effects of VEGF receptor inhibition on the immune response were performed in rapidly growing tumor models where immune equilibrium is not established before treatment.

Paraneoplastic Encephalitis Associated with Locally Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.

Paraneoplastic neurologic diseases (PND) are rare but can occur in patients with common malignancies including breast cancer. In patients with hormone receptor (HR)-negative human epidermal growth factor receptor 2 (HER2)-positive breast cancer, PND have been reported in association with anti-Yo antibodies and with clinical presentation of paraneoplastic cerebellar degeneration. We describe the case of a woman with progressively altered mental status and seizures, ultimately requiring admission.

Inhibition of BRAF and ERK1/2 has synergistic effects on thyroid cancer growth in vitro and in vivo.

Mutations in the BRAF gene are highly prevalent in thyroid cancer. However, the response rate of thyroid tumors to BRAF-directed therapies has been mixed. Increasingly, combination therapies inhibiting the MAPK pathway at multiple nodes have shown promise.

Establishment and Characterization of Four Novel Thyroid Cancer Cell Lines and PDX Models Expressing the RET/PTC1 Rearrangement, BRAFV600E, or RASQ61R as Drivers.

Cancer cell lines are critical models to study tumor progression and response to therapy. In 2008, we showed that approximately 50% of thyroid cancer cell lines were redundant or not of thyroid cancer origin. We therefore generated new authenticated thyroid cancer cell lines and patient-derived xenograft (PDX) models using and feeder cell approaches, and characterized these models and .

Oncocytic variant of medullary thyroid carcinoma; a rare tumor with numerous diagnostic mimics by fine needle aspiration.

Oncocytic variant of medullary thyroid carcinoma is rare form of thyroid carcinoma that is easily misdiagnosed on fine needle aspiration specimens due to it is low incidence and cytomorphologic overlap with other more common Hurtle cell lesions. A correct initial diagnosis by fine needle aspiration is imperative as the clinical treatment for medullary carcinoma differs significantly from the mimickers. We present a case of this rare variant tumor that on initial fine needle aspiration was described as a Hurthle cell lesion and was subsequently correctly classified on the resection specimen.

Metastatic Urothelial Carcinoma to the Uterine Cervix: A Case Report of a Rare Entity and Review of the Diagnostic Differential.

Urothelial carcinoma (UC) rarely metastasizes to the gynecologic tract, occurring in descending order of frequency, within the vagina, uterus, ovaries, and cervix. Significant morphologic overlap exists between primary gynecologic squamous lesions (both benign and malignant) and metastatic UC, thus potentially hindering a timely and accurate diagnosis. We present a case of UC metastatic to the uterine cervix in a 69-year-old female initially found to have noninvasive high-grade papillary UC of the bladder.

Fibroblast Subtypes Regulate Responsiveness of Luminal Breast Cancer to Estrogen.

Antiendocrine therapy remains the most effective treatment for estrogen receptor-positive (ER) breast cancer, but development of resistance is a major clinical complication. Effective targeting of mechanisms that control the loss of ER dependency in breast cancer remains elusive. We analyzed breast cancer-associated fibroblasts (CAF), the largest component of the tumor microenvironment, as a factor contributing to ER expression levels and antiendocrine resistance.

Discordance Between Intraoperative Consultation by Frozen Section and Final Diagnosis.

Discrepancies between intraoperative consultations with frozen section diagnosis and the final pathology report have the potential to alter treatment decisions and affect patient care. Monitoring these correlations is a key component of laboratory quality assurance, however identifying specific areas for improvement can be difficult to attain. Our goal is to develop a standardized method utilizing root cause analysis and a modified Eindhoven classification schematic to identify the source of discrepancies and deferrals and subsequently to guide performance improvement initiatives.

FAK Expression, Not Kinase Activity, Is a Key Mediator of Thyroid Tumorigenesis and Protumorigenic Processes.

Unlabelled: There are limited therapy options for advanced thyroid cancer, including papillary and anaplastic thyroid cancer (PTC and ATC). Focal adhesion kinase (FAK) regulates cell signaling by functioning as a scaffold and kinase. Previously, we demonstrated that FAK is overexpressed and activated in thyroid cancer cells and human PTC clinical specimens.

Tumor-Infiltrating T Cells and the PD-1 Checkpoint Pathway in Advanced Differentiated and Anaplastic Thyroid Cancer.

Context: Five to 10% of patients with differentiated thyroid cancers (DTC) develop invasive and/or distant metastatic disease that is marginally improved with standard therapies. Prognosis is poor for patients with anaplastic thyroid cancer, with a median survival of 3-5 months. We suggest that a paradigm shift is necessary in the treatment of advanced cases.

The clinical impact of immediate on-site cytopathology evaluation during endoscopic ultrasound-guided fine needle aspiration of pancreatic masses: a prospective multicenter randomized controlled trial.

Objectives: Observational data on the impact of on-site cytopathology evaluation (OCE) during endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) of pancreatic masses have reported conflicting results. We aimed to compare the diagnostic yield of malignancy and proportion of inadequate specimens between patients undergoing EUS-FNA of pancreatic masses with and without OCE.

Methods: In this multicenter randomized controlled trial, consecutive patients with solid pancreatic mass underwent randomization for EUS-FNA with or without OCE.

Characterization of thyroid cancer cell lines in murine orthotopic and intracardiac metastasis models.

Thyroid cancer incidence has been increasing over time, and it is estimated that ∼1950 advanced thyroid cancer patients will die of their disease in 2015. To combat this disease, an enhanced understanding of thyroid cancer development and progression as well as the development of efficacious, targeted therapies are needed. In vitro and in vivo studies utilizing thyroid cancer cell lines and animal models are critically important to these research efforts.

PD-1+Tim-3+ CD8+ T Lymphocytes Display Varied Degrees of Functional Exhaustion in Patients with Regionally Metastatic Differentiated Thyroid Cancer.

Regional metastatic differentiated thyroid cancer (mDTC) provides a unique model in which to study the tumor-immune interface. These lymph node metastases persist for years, generally without progression to distant metastases. Although the immune system likely impedes disease progression, it is unsuccessful in eliminating disease.

Massive dissemination from spinal cord gangliogliomas negative for BRAF V600E: report of two rare adult cases.

Objectives: Metastatic leptomeningeal spread from spinal cord gangliogliomas (GGs) is exceedingly rare.

Methods: Two adult women, aged 27 and 51 years, died of massive disseminations of cervicothoracic GGs 4 and 6 years, respectively, after initial diagnoses; full autopsies were performed. BRAF status was assessed by VE1 immunohistochemistry (IHC), Sanger sequencing, and a single-nucleotide base extension assay (SNaPshot, Applied Biosystems, Princeton, NJ).

Thioredoxin interacting protein (TXNIP) is a novel tumor suppressor in thyroid cancer.

Background: Thyroid cancer is the most common endocrine malignancy, and many patients with metastatic differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC) fail to respond to conventional therapies, resulting in morbidity and mortality. Additional therapeutic targets and treatment options are needed for these patients. We recently reported that peroxisome proliferator-activated receptor gamma (PPARγ) is highly expressed in ATC and confers an aggressive phenotype when overexpressed in DTC cells.

The role of cytology specimens in molecular testing of solid tumors: techniques, limitations, and opportunities.

Numerous studies have demonstrated the suitability of cytology specimens for molecular analysis. When combined with the ability to acquire tissue in a minimally invasive manner, testing on cytology specimens is an especially attractive method for further refining diagnosis, determining prognosis, and predicting likely response to therapy as well as monitoring disease. As the demand for testing of small specimens increases, the burden of determining whether a specimen should be referred for testing will increasingly be placed on the pathologist.

Targeted inhibition of Src kinase with dasatinib blocks thyroid cancer growth and metastasis.

Purpose: There are no effective therapies for patients with poorly differentiated papillary thyroid cancer (PTC) or anaplastic thyroid cancer (ATC), and metastasis to the bone represents a significantly worse prognosis. Src family kinases (SFKs) are overexpressed and activated in numerous tumor types and have emerged as a promising therapeutic target, especially in relation to metastasis. We recently showed that Src is overexpressed and activated in thyroid cancer.

Liquid-based Papanicolaou tests in endometrial carcinoma diagnosis. Performance, error root cause analysis, and quality improvement.

Recent reports show that the sensitivity of endometrial carcinoma detection on liquid-based Papanicolaou (Pap) tests (88%) is considerably higher than that reported on conventional Pap smears (20%-30%), although few laboratories have corroborated these results. We performed a 5-year retrospective review of all liquid-based Pap tests (n = 69) in women who later were given a diagnosis of endometrial carcinoma, performed error root cause analysis, and developed quality improvement initiatives as a means of error reduction. The original and rescreened Pap test sensitivity rates for endometrial carcinoma were 31.