Ultrasound for the detection of the pyramidal lobe of the thyroid gland.

Purpose: The pyramidal lobe (PL) is an ancillary lobe of the thyroid gland that can be affected by the same pathologies as the rest of the gland. We aimed to assess the diagnostic performance of high-resolution sonography in the detection of the PL with verification by dissection and histological examination.

Methods: In a prospective, cross-sectional mono-center study, 50 fresh, non-embalmed cadavers were included.

Omission of lateral lymph node dissection in medullary thyroid cancer without a desmoplastic stromal reaction.

Background: Medullary thyroid cancer can be subdivided during surgery into tumours with or without a desmoplastic stromal reaction (DSR). DSR positivity is regarded as a sign of disposition to metastasize. The aim of this study was to analyse whether lateral lymph node dissection can be omitted in patients with DSR-negative tumours.

The 40bp Indel Polymorphism rs150550023 in the Promoter is Associated with Intriguing Shifts in Gene Expression in the p53-MDM2 Regulatory Hub.

Most low-penetrance genetic risk factors for cancer are located in noncoding regions, presumably altering the regulation of neighboring genes. The poorly characterized Indel polymorphism rs150550023 (rs3730485; del1518) in the promoter of (human homolog of mouse double minute 2) is a biologically plausible candidate genetic risk factor, which might influence the expression of , a key negative regulator of the central tumor suppressor p53. Here, we genotyped rs150550023 in a Central European hospital-based case-control study of 407 breast cancer patients and 254 female controls.

Expression of somatostatin receptor 2A in medullary thyroid carcinoma is associated with lymph node metastasis.

Medullary carcinoma (MTC) is an aggressive tumour that derives from the thyroid parafollicular calcitonin-secreting cells (C cells). Lymph node metastasis may occur early in disease pathogenesis and is one of the most important negative prognostic parameters. Surgery is the only curative therapy while chemotherapeutic options are limited.

Expression of hypoxia-associated proteins in sporadic medullary thyroid cancer is associated with desmoplastic stroma reaction and lymph node metastasis and may indicate somatic mutations in the VHL gene.

Medullary thyroid carcinomas (MTCs) are mostly aggressive but slowly growing malignant tumours that metastasize early to loco-regional lymph nodes. Desmoplastic stroma reaction is a strong risk factor associated with lymph node metastases. We evaluated immunohistochemically the expression of two hypoxia-associated proteins, carbonic anhydrase IX (CAIX) and hypoxia-induced factor 1α (HIF1α), and ki-67, intercellular matrix adhesion molecule E-cadherin and the stroma remodelling marker tenascin C in a series of 100 sporadic MTCs and corresponding lymph node metastases, if present.

Lipoxygenase mediates invasion of intrametastatic lymphatic vessels and propagates lymph node metastasis of human mammary carcinoma xenografts in mouse.

In individuals with mammary carcinoma, the most relevant prognostic predictor of distant organ metastasis and clinical outcome is the status of axillary lymph node metastasis. Metastases form initially in axillary sentinel lymph nodes and progress via connecting lymphatic vessels into postsentinel lymph nodes. However, the mechanisms of consecutive lymph node colonization are unknown.

Desmoplastic stromal reaction in papillary thyroid microcarcinoma.

Aims: To evaluate the value of a desmoplastic stromal reaction (desmoplasia) as an indicator of metastasis in papillary thyroid microcarcinoma.

Methods And Results: One hundred and nine cases of papillary thyroid microcarcinoma from the pathological archive of the Medical University of Vienna, Austria were analysed for the presence of desmoplasia in relation to other morphological and clinicopathological parameters. Eighty-one of 109 papillary microcarcinomas showed a desmoplastic stromal reaction.

Identification of SERPINA1 as single marker for papillary thyroid carcinoma through microarray meta analysis and quantification of its discriminatory power in independent validation.

Background: Several DNA microarray based expression signatures for the different clinically relevant thyroid tumor entities have been described over the past few years. However, reproducibility of these signatures is generally low, mainly due to study biases, small sample sizes and the highly multivariate nature of microarrays. While there are new technologies available for a more accurate high throughput expression analysis, we show that there is still a lot of information to be gained from data deposited in public microarray databases.

Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters.

As incidence data on gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have so far only been retrospectively obtained and based on inhomogeneous material, we conducted a prospective study in Austria collecting all newly diagnosed GEP-NETs during 1 year. Using the current WHO classification, the tumor, nodes, metastases (TNM) staging and Ki67 grading and the standard diagnostic procedure proposed by the European Neuroendocrine Tumor Society (ENETS), GEP-NETs from 285 patients (male: 148; female: 137) were recorded. The annual incidence rates were 2.

Indeterminate thyroid nodules: a challenge for the surgical strategy.

Background: Because no clinical parameter can establish the final status of a cytologically indeterminate thyroid nodule (ITN) or nodal-metastases in case of malignancy, the initial surgical strategy should define an oncologically adequate procedure with low morbidity.

Methods: The prognostic relevance of sex, age, tumor sizes, multifocality, thyroid function, and recurrence was analyzed in 156 consecutive patients according to the presence of malignancy and nodal metastases. The accuracy of frozen sections to reveal malignancy was determined.

Tenascin C in medullary thyroid microcarcinoma and C-cell hyperplasia.

Tenascin C (Tn-C) is an extracellular matrix glycoprotein that is expressed early in carcinogenesis including intraepithelial neoplastic lesions of different organs. In this study, we analyze whether stroma reaction seen by Tn-C expression is detected early in tumorigenesis of medullary thyroid carcinoma (MTC) including medullary microcarcinoma and C-cell hyperplasia (CCH), which is accepted to be a precursor lesion of MTC in the setting of RET oncogene germ-line mutation. Tn-C was expressed in the stroma of all medullary microcarcinoma and in the stroma next to CCH.

Follicular thyroid carcinoma in an iodine-replete endemic goiter region: a prospectively collected, retrospectively analyzed clinical trial.

Objective: To determine risk factors for presence of lymph node or distant metastases in patients with follicular thyroid cancer (FTC) at the time of diagnosis and whether there is a relationship between the type of tumor invasion and metastases.

Summary Background Data: FTC often presents distant metastases at the initial diagnosis. As distant metastases are independent prognostic factors in a patient's survival, determination of clinicopathologic characteristics for patients who are at higher risk for developing metastases is of greater clinical importance.

Hedgehog signaling is involved in differentiation of normal colonic tissue rather than in tumor proliferation.

The Hedgehog (Hh) pathway is a main regulation cascade in embryonic differentiation. It is also present in adult tissues and unusual expression has been associated with formation of benign and malignant lesions. We examined the presence of the Hedgehog pathway in normal and pathological human colon tissue.

Diagnostic value of sonography, ultrasound-guided fine-needle aspiration cytology, and diffusion-weighted MRI in the characterization of cold thyroid nodules.

Introduction: The purpose of this prospective study was to assess the diagnostic value of different modalities for the characterization of cold thyroid nodules.

Methods: In 35 patients with cold nodules, thyroid carcinoma was suspected on scintigraphy. These patients were prospectively investigated with sonography, ultrasound-guided fine-needle aspiration (USgFNA), and quantitative diffusion-weighted imaging magnetic resonance imaging (DWI) (navigated echo-planar imaging; maximum b-value 800s/mm(2)) prior to surgery.

Insulinomatosis: a multicentric insulinoma disease that frequently causes early recurrent hyperinsulinemic hypoglycemia.

Background: Multicentric insulinoma disease was characterized with regard to its histopathology, multiple endocrine neoplasia type 1 (MEN1) status, precursor lesions, and the risk of hyperinsulinemic hypoglycemia recurrence.

Methods: Fourteen patients with multicentric insulinoma disease were compared with 267 patients with sporadic and familial insulinomas. The tumors were classified according to the World Health Organization (WHO) criteria.

Sporadic hypercalcitoninemia: clinical and therapeutic consequences.

'Calcitonin screening' is not accepted as the standard of care in daily practice. The clinical and surgical consequences of 'calcitonin screening' in a series of patients with mildly elevated basal calcitonin and pentagastrin stimulated calcitonin levels are presented. 260 patients with elevated basal (>10 pg/ml) and stimulated calcitonin levels (>100 pg/ml) were enrolled in this prospective study.

The influence of gender, age, and RET polymorphisms on C-cell hyperplasia and medullary thyroid carcinoma.

Background: RET germline mutations predispose to the development of hereditary medullary thyroid carcinoma (hMTC). Several single nucleotide polymorphisms (SNPs) are described associated with sporadic MTC (sMTC). However, the findings regarding their influence on the clinical course and biological behavior of this disorder are discordant.

Can quantitative diffusion-weighted MR imaging differentiate benign and malignant cold thyroid nodules? Initial results in 25 patients.

Background And Purpose: The characterization of cold nodules of the thyroid gland is mandatory because approximately 20% of these nodules are of malignant origin. The purpose of this study was to evaluate the distinction of cold thyroid nodules by using quantitative diffusion-weighted MR imaging (DWI).

Materials And Methods: In 25 patients with cold nodules on scintigraphy and suggestive findings at fine-needle aspiration, thyroid carcinoma was suggested.

Desmoplasia in medullary thyroid carcinoma: a reliable indicator of metastatic potential.

Aims: To evaluate the reliability of desmoplasia as a reproducible morphological parameter indicating the metastatic potential of medullary thyroid carcinoma (MTC).

Methods And Results: One hundred and twenty cases of MTC of the Medical University of Vienna, Austria and 76 cases from the School of Medicine of Marseille, France were analysed for the presence of desmoplastic stroma reaction by four endocrine pathologists. Intra- and interobserver concordance was assessed.

Medullary thyroid microcarcinoma recommendations for treatment - a single-center experience.

Background: Conflicting recommendations exist regarding lymph node (LN) surgery in microMTC (
Methods: Patients with elevated basal (bCT:>or=10pg/ml) and pentagastrin-stimulated calcitonin levels (sCT:>100pg/ml) were selected for initial surgery.

Comparison of RNA amplification techniques meeting the demands for the expression profiling of clinical cancer samples.

Available ribonucleic acid (RNA) amplification methods are extensively tested for reproducibility, but only a few studies additionally deal with potential amplification bias. On targeted arrays, we evaluated three amplification protocols, which are less time consuming than the commonly used T7-RNA polymerase based in vitro transcription protocols and therefore may be more suitable for clinical use: Template-switching polymerase chain reaction (PCR), Ribo-single primer isothermal amplification and a random primer-based PCR. Additionally, a more sensitive labelling method, Dendrimer labelling, was evaluated.

Molecular characterization of the desmoplastic tumor stroma in medullary thyroid carcinoma.

Medullary thyroid carcinomas are aggressive neoplasias that metastasize very early to loco-regional lymph nodes, and tumors with a desmoplastic stromal reaction have a higher incidence of lymph node metastasis. In order to characterize the desmoplastic response in thyroid cancers, we evaluated the expression pattern of three molecular markers of activated fibroblasts/myofibroblasts, namely, fibroblast activation protein alpha (FAPalpha), tenascin-C (Tn-C), and alpha-smooth muscle actin (alpha-SMA), as well as the endothelial markers endoglyx-1, CD34 and CD31 in a series of 28 metastatic and non-metastatic medullary thyroid cancers. Immunohistochemical studies demonstrated that the three fibroblast activation markers (FAPalpha, Tn-C, alpha-SMA) are consistently expressed in the peritumoral and intratumoral stromal compartment of medullary thyroid carcinomas and expression of FAPalpha and Tn-C correlated with the degree of desmoplasia determined histologically (p=0.

Proteomic expression profiling of thyroid neoplasms.

Thyroid cancer is the most common endocrine neoplasm with multiple histologic subtypes, each associated with different treatments and outcomes. Differentiating benign neoplasms such as follicular adenomas from malignant entities such as follicular carcinomas and papillary carcinoma can be challenging. To define the proteomic profile of different thyroid tumors, we screened an antibody array of 330 features against five thyroid neoplasms: follicular adenoma, follicular carcinoma, papillary carcinoma, anaplastic carcinoma, and medullary carcinoma as well as normal thyroid epithelium.

The value of intraoperative pentagastrin testing in medullary thyroid cancer.

Background: The decrease of calcitonin levels after curative operation in patients with medullary thyroid cancer is characterized by individual variation; therefore, intraoperative calcitonin measurements to evaluate the completeness of the resection seem to not be feasible. The aim of this study was to evaluate whether an intraoperative pentagastrin test after thyroidectomy and central neck dissection is useful to predict lymph node involvement of the lateral neck.

Methods: A group of 30 consecutive patients underwent primary surgery.