A Retrospective Evaluation of the Diagnostic Performance of an Interdependent Pairwise MicroRNA Expression Analysis with a Mutation Panel in Indeterminate Thyroid Nodules.

The addition of genetic analysis to the evaluation of thyroid nodule fine-needle aspiration biopsy samples improves diagnostic accuracy of cytologically indeterminate thyroid nodules (ITNs) with Bethesda III or IV cytopathology. We previously reported the performance of a multiplatform molecular test, referred to in this study as MPTXv1, that includes a mutation panel (ThyGeNEXT) plus an algorithmic microRNA (miRNA) risk classifier (ThyraMIR). Complex interactions of growth-promoting and -suppressing miRNAs affect the phenotype.

Analytical and clinical validation of pairwise microRNA expression analysis to identify medullary thyroid cancer in thyroid fine-needle aspiration samples.

Background: Medullary thyroid carcinoma (MTC) is an aggressive malignancy originating from the parafollicular C cells. Preoperatively, thyroid nodule fine-needle aspiration cytology (FNAC) and pathogenic gene mutations are definitive in approximately one-half of cases. MicroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNAs that regulate gene expression, a characteristic that confers the potential for identifying malignancy.

Structural alterations in tumor-draining lymph nodes before papillary thyroid carcinoma metastasis.

Background: The purpose of this study was to define and characterize the thyroid tumor-draining lymph nodes in genetically engineered mice harboring thyroid-specific expression of oncogenic Braf with and without Pten insufficiency.

Methods: After intratumoral injection of methylene blue, the lymphatic drainage of the thyroid gland was visualized in real time. The thyroid gland/tumor was resected en bloc with the respiratory system for histological analysis.

Rapid on-site evaluation of EBUS-TBNA specimens of lymph nodes: Comparative analysis and recommendations for standardization.

Background: There is no widely accepted rapid on-site evaluation (ROSE) reporting system for endobronchial ultrasound-guided transbronchial needle aspiration. At the University of Arkansas for Medical Sciences, ROSE reporting was unstructured. The goal was to evaluate, compare, and improve upon 2 structured approaches proposed in the literature.

Herpes simplex infection of the larynx requiring laryngectomy.

Herpes simplex virus infection of the larynx is an exceedingly rare clinical entity, most frequently reported in the pediatric population or in immunocompromised adults. We present a 62-year-old woman presented with neck pain, hoarseness, crepitus over the larynx, and what appeared to be a necrotic mass of the right true vocal cord on laryngoscopy. Due to near-complete destruction of the cartilaginous framework of the larynx, a total laryngectomy was performed.

A novel strategy to inhibit FAK and IGF-1R decreases growth of pancreatic cancer xenografts.

Deregulation of insulin-like growth factor-1 receptor (IGF-1R) and focal adhesion kinase (FAK) signaling pathways plays an important role in cancer cell proliferation and metastasis. In pancreatic cancer cells, the crosstalk and compensatory mechanisms between these two pathways reduce the efficacy of the treatments that target only one of the pathways. Ablation of IGF-1R signaling by siRNA showed minimal effects on the survival and growth of pancreatic cancer cells.

A novel small molecule inhibitor of FAK decreases growth of human pancreatic cancer.

Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that is overexpressed in many types of tumors, including pancreatic cancer, and plays an important role in cell adhesion and survival signaling. Pancreatic cancer is a lethal disease and is very resistant to chemotherapy, and FAK has been shown recently to assist in tumor cell survival. Therefore, FAK is an excellent potential target for anti-cancer therapy.

Vascular endothelial growth factor receptor-3 promotes breast cancer cell proliferation, motility and survival in vitro and tumor formation in vivo.

Vascular endothelial growth factor receptor-3 is a receptor tyrosine kinase that is overexpressed in some human carcinomas, but its role in tumorigenesis has not been fully elucidated. We examined VEGFR-3 expression in normal, nonneoplastic and early stage malignant breast tissues and have shown that VEGFR-3 upregulation in breast cancer preceded tumor cell invasion, suggesting that VEGFR-3 may function as a survival signal. We characterized the biological effects of VEGFR-3 over-expression in human breast cancer cells based on two approaches: gain of function by overexpressing VEGFR-3 in MCF-7 breast cancer cells and loss of function by RNAi-mediated silencing of VEGFR-3 in MCF-7-VEGFR-3 and BT474 cells.

Focal adhesion kinase expression in human neuroblastoma: immunohistochemical and real-time PCR analyses.

Purpose: The focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase important in signaling between cells and their extracellular matrix. Studies have shown that FAK expression is up-regulated in several human tumors and is related to tumor progression. We recently found an increase in p125(FAK) expression in human neuroblastoma cells lines and wished to determine its expression in human neuroblastoma specimens and evaluate for a possible correlation between p125(FAK) expression and known prognostic factors for neuroblastoma.

The utility of p16(Ink4a) in discriminating between cervical intraepithelial neoplasia 1 and nonneoplastic equivocal lesions of the cervix.

Context: The protein p16(Ink4a) is overexpressed in cervical lesions associated with high-risk human papillomavirus (HPV) subtypes 16 and 18, but not in low-risk HPV subtypes 6 and 11 or non-HPV-associated cervical lesions.

Objective: To determine whether p16(Ink4a) expression in equivocal cervical lesions helps distinguish atypical non-HPV changes from HPV-related changes.

Design: One hundred ninety-one cervical lesions, including 81 cervical intraepithelial neoplasia 1, 52 squamous metaplasia, 33 cellular features suggestive of HPV-related change, 9 reserve cell hyperplasia, 4 microglandular hyperplasia, and 12 inflammatory cervicitis, were randomly selected from archival cervical biopsy specimens.

Stage IA vulvar squamous cell carcinoma: an analysis of tumor invasive characteristics and risk.

Early invasive vulvar squamous cell carcinoma (SCC) with less than 1.0 mm of invasion (FIGO stage IA) has been shown to have a minimal risk of lymph node metastasis and is associated with an excellent prognosis. The prognostic significance of other histologic parameters other than depth of invasion, however, remains controversial.

The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer.

Tissue transglutaminase (TG2) is a ubiquitously expressed enzyme capable of catalyzing protein cross-links. TG2-dependent cross-links are important in extracellular matrix integrity and it has been proposed that this TG2 activity establishes a barrier to tumor spread. Furthermore, TG2 controls sensitivity to the chemotherapeutic drug doxorubicin.

p53 regulates FAK expression in human tumor cells.

Attenuation of the p53 protein is one of the most common abnormalities in human tumors. Another important marker of tumorigenesis is focal adhesion kinase (FAK), a 125-kDa tyrosine kinase that is overexpressed at the mRNA and protein levels in a variety of human tumors. FAK is a critical regulator of adhesion, motility, metastasis, and survival signaling.

Molecular and morphologic distinctions between infiltrating ductal and lobular carcinoma of the breast.

Histopathologic distinction between ductal and lobular carcinomas of the breast has been made since 1941. Together, these two subtypes account for >95% of all mammary carcinomas. With the recent advances in molecular techniques, our understanding of the biology behind these carcinomas has greatly expanded.

Lipogranuloma of the cervix.

OBJECTIVE.: A case report of lipogranuloma of the cervix with review of the literature is reported. MATERIALS AND METHODS.

Perceptions of diagnostic terminology and cytopathologic reporting of fine-needle aspiration biopsies of thyroid nodules: a survey of clinicians and pathologists.

Introduction: Guidelines on thyroid fine-needle aspiration biopsy (FNABs) reporting calls for unambiguous diagnostic terminology in order to maximize treatment. This study evaluates how pathologists follow the guidelines and clinicians understand the diagnostic categories in terms of patient care.

Design: Survey 1 asked pathologists who perform/interpret FNABs which of "atypical," "indeterminate," "suspicious," and "nondiagnostic" they routinely use.

Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression.

Cystatin M is a secreted inhibitor of lysosomal cysteine proteases. Several lines of evidence indicate that cystatin M is a tumor suppressor important in breast malignancy; however, the mechanism(s) that leads to inactivation of cystatin M during cancer progression is unknown. Inspection of the human cystatin M locus uncovered a large and dense CpG island within the 5' region of this gene (termed CST6).

Validation of a five-tier cytodiagnostic system for thyroid fine needle aspiration biopsies using cytohistologic correlation.

Objective: Approximately 70-80% of thyroid fine needle aspiration biopsies (FNAB) can distinguish benign from malignant thyroid nodules. However, much interpretive diagnostic difficulty arises with the remaining 20-30% of cases. These problematic thyroid aspirations have been placed in various diagnostic categories, which collectively have led to confusion and a negative impact on the clinical management of patients with thyroid nodules.

The impact of assessing specimen adequacy and number of needle passes for fine-needle aspiration biopsy of thyroid nodules.

Fine-needle aspiration biopsy (FNAB) of thyroid nodules is a safe, cost-effective procedure but the rates of inadequate cytology specimens range from approximately 1% to 15%. This study tests the hypothesis that ultrasonographically (US) guided FNAB and onsite assessment of cytology improves the adequacy rate of FNAB. A retrospective analysis was performed on 693 thyroid FNAB specimens obtained with and without ultrasound guidance and with or without onsite cytology assessment.

Uterine-like mass with features of an extrauterine adenomyoma presenting 22 years after total abdominal hysterectomy-bilateral salpingo-oophorectomy: a case report and review of the literature.

Adenomyoma is a benign tumor composed of smooth muscle and benign endometrium. These tumors typically originate within the uterus. An extrauterine adenomyoma is a rare entity.

Characterization of papillary squamotransitional cell carcinoma of the cervix.

Objective: Does papillary squamotransitional cell carcinoma (PSTCC) behave differently from conventional squamous cell carcinoma of the cervix and does PSTCC have true transitional cell differentiation?

Materials And Methods: Twenty cases of PSTCC were identified from archival files. Clinical data were compiled. Immunoperoxidase stains for uroplakin III, p63 and p16 were performed on available tissue blocks.

Human papillomavirus infection and p16(INK4a) protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma.

Objective: Vulvar intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. The purpose of this study was to investigate the functional properties of VIN related to expression of p16(INK4a) protein as well as to detection of human papillomavirus (HPV) type 16 by real-time polymerase chain reaction (RT-PCR) analysis.

Methods: A total of 49 vulvar biopsy samples were examined by hematoxylin-eosin staining from benign/reactive lesions, condyloma acuminatum, VIN, and invasive squamous cell carcinoma (SCC).

Association between invasive squamous cell carcinoma of the vulva and ABO blood group.

Objective: To determine whether the distribution of ABO blood group among women with invasive squamous cell carcinoma (SCC) of the vulva is different from that among a population of women treated for nonneoplastic gynecologic disease.

Methods: A retrospective analysis of pathology reports and blood bank records from January 1996 through September 2003 was performed. The distribution of ABO blood group for 33 women diagnosed with invasive SCC of the vulva was determined.