The cadherin–catenin complex in nasopharyngeal carcinoma

Abnormal Wnt signaling and impaired cell–cell adhesion due to abnormal E-cadherin and b-catenin func tion have been implicated in many cancers, but have not been fully explored in nasopharyngeal carcinoma. The aim of this study was to analyze b-Catenin cellular location and E-cadherin expression levels in nasopharyngeal carcinoma. E-cadherin expression levels were also correlated with clinical data and underlying pathology. b-Catenin and E-cadherin expression were examined in 18 nasopharyn geal carcinoma and 7 non-tumoral inflammatory pharynx tissues using immunohistochemical methods. Patient clin ical data were collected, and histological evaluation was performed by hematoxylin/eosin staining. b-catenin was detected in membrane and cytoplasm in all cases of naso pharyngeal carcinoma, regardless of histological type; in non-tumoral tissues, however, b-catenin was observed only in the membrane. As for E-cadherin expression levels, strong staining was observed in most non-tumoral tissues, but staining was only moderate in nasopharyngeal carci noma tissues. E-cadherin expression was associated with b-catenin localization, study group, metastatic disease, and patient outcomes. Reduced levels of E-cadherin protein observed in nasopharyngeal carinoma may play an important role in invasion and metastasis. Cytoplasmic b-catenin in nasopharyngeal carcinoma may impair cell– cell adhesion, promoting invasive behavior and a metastatic tumor phenotype

Clonal patterns in phaeochromocytomas and MEN-2A adrenal medullary hyperplasias: histological and kinetic correlates

The relationship among histological features, cell kinetics, and clonality has not been studied in adrenal medullary hyperplasias (AMHs) and phaeochromocytomas (PCCs). Thirty-four PCCs (23 sporadic and 11 MEN-2A (multiple endocrine neoplasia type 2A)-related tumours, the latter associated with AMH) from females were included in this study. Representative samples were histologically evaluated and microdissected to extract DNA and evaluate the methylation pattern of the androgen receptor alleles. At least two tissue samples (from the peripheral and internal zones in each tumour) were analysed with appropriate tissue controls run in every case. The same areas were selected for MIB-1 staining and in situ end labelling (ISEL). Malignant PCCs were defined by histologically confirmed distant metastases. All monoclonal AMH nodules from the same patient showed the same X-chromosome inactivated. Six sporadic PCCs revealed liver metastases (malignant PCC) and eight additional sporadic PCCs showed periadrenal infiltration (locally invasive PCC). All informative PCCs were monoclonal, except for five locally invasive PCCs and one benign PCC that revealed polyclonal patterns. Those cases also showed a fibroblastic stromal reaction with prominent blood vessels, focal smooth muscle differentiation, and significantly higher MIB-1 (126.8±29.9) and ISEL (50.9±12.8) indices. Concordant X-chromosome inactivation in nodules from a given patient suggests that MEN-2A AMH is a multifocal monoclonal condition. A subgroup of PCCs characterized by balanced methylation of androgen receptor alleles, high cellular turnover, and stromal proliferation also shows locally invasive features. Copyright © 2000 John Wiley & Sons, Ltd

cDNA Sequence and Genomic Structure of the Rat Ret Proto-Oncogene

The RET proto-oncogene, a member of the Receptor Tyrosine Kinase family, plays a crucial role during the development of the excretory system and the enteric nervous system, as demonstrated by in vivo animal studies and by its involvement in the pathogenesis of several human neurocristopathies like Hirschsprung disease and Multiple Endocrine Neoplasia type 2. Using a multistep RT-PCR approach we have isolated and sequenced the cDNA of the whole rat RET proto-oncogene, reporting the deduced amino acid sequence in comparison with the human and mouse counterparts. Moreover, two different isoforms (RET9 and RET51) have been confirmed in the rat, while a third RET isoform demonstrated in human (RET43) has not resulted to be conserved in this species. Finally, we have determined the genomic structure of the rat RET proto-oncogene comparing the exon-intron boundaries and intron sizes with the known structure of the human homologous gene. Our findings will facilitate the molecular study of appropriate rat models of RET related human diseases

Inmunohistochemical Profile of Solid Cell Nest of Thyroid Gland

It is widely held that solid cell nests (SCN) of the thyroid are ultimobranchial body remnants. SCNs are composed of main cells and C cells. It has been suggested that main cells might be pluripotent cells contributing to the histogenesis of C cells and follicular cells, as well as to the formation of certain thyroid tumors. The present study sought to analyze the immunohistochemical profile of SCN and to investigate the potential stem cell role of SCN main cells. Tissue sections from ten cases of nodular hyperplasia (non-tumor goiter) with SCNs were retrieved from the files of the Hospital Infanta Luisa (Seville, Spain). Parathormone (PTH), calcitonin (CT), thyroglobulin (TG), thyroid transcription factor (TTF-1), galectin 3 (GAL3), cytokeratin 19 (CK 19), p63, bcl-2, OCT4, and SALL4 expression were evaluated by immunohistochemistry. Patient clinical data were collected, and tissue sections were stained with hematoxylin–eosin for histological examination. Most cells stained negative for PTH, CT, TG, and TTF-1. Some cells staining positive for TTF-1 and CT required discussion. However, bcl-2, p63, GAL3, and CK 19 protein expression was detected in main cells. OCT4 protein expression was detected in only two cases, and SALL4 expression in none. Positive staining for bcl-2 and p63, and negative staining for PTH, CT, and TG in SCN main cells are both consistent with the widely accepted minimalist definition of stem cells, thus supporting the hypothesis that they may play a stem cell role in the thyroid gland, although further research will be required into stem cell markers. Furthermore, p63 and GAL-3 staining provides a much more sensitive means of detecting SCNs than staining for carcinoembryonic antigen, calcitonin, or other markers; this may help to distinguish SCNs from their mimics

The cadherin–catenin complex in nasopharyngeal carcinoma

Abnormal Wnt signaling and impaired cell–cell adhesion due to abnormal E-cadherin and β-catenin function have been implicated in many cancers, but have not been fully explored in nasopharyngeal carcinoma. The aim of this study was to analyze β-Catenin cellular location and E-cadherin expression levels in nasopharyngeal carcinoma. E-cadherin expression levels were also correlated with clinical data and underlying pathology. β-Catenin and E-cadherin expression were examined in 18 nasopharyngeal carcinoma and 7 non-tumoral inflammatory pharynx tissues using immunohistochemical methods. Patient clinical data were collected, and histological evaluation was performed by hematoxylin/eosin staining. β-catenin was detected in membrane and cytoplasm in all cases of nasopharyngeal carcinoma, regardless of histological type; in non-tumoral tissues, however, β-catenin was observed only in the membrane. As for E-cadherin expression levels, strong staining was observed in most non-tumoral tissues, but staining was only moderate in nasopharyngeal carcinoma tissues. E-cadherin expression was associated with β-catenin localization, study group, metastatic disease, and patient outcomes. Reduced levels of E-cadherin protein observed in nasopharyngeal carinoma may play an important role in invasion and metastasis. Cytoplasmic β-catenin in nasopharyngeal carcinoma may impair cell–cell adhesion, promoting invasive behavior and a metastatic tumor phenotype

Micrometástasis. Ganglio centinela

Micrometástasis. Ganglio centinela

Incidenza della vertigine parossistica benigna bilaterale e monolaterale in caso di positività alla manovra Dix-Hallpike a destra e sinistra: modello basato sul verso del nistagmo rotatorio

Patients presenting with nystagmus indicative of benign paroxysmal positional vertigo (BPPV) during the left and the right Dix-Hallpike manoeuvres (DHMs) are frequently seen in clinical practice. In such cases, BPPV may be unilateral or bilateral. The aim of this study is to describe the incidence of unilateral and bilateral BPPV when both DHMs are positive, taking into account the sense of the torsional component of nystagmus. This is a prospective multicentre study. BPPV patients were classified into three groups: patients with only one positive DHM (control group, CG), patients showing positive bilateral DHM with nystag - mus in the same sense in both DHMs (same sense group, SSG) and patients showing posi - tive bilateral DHM with the torsional component of nystagmus beating in opposite senses in each DHM (opposite sense group, OSG). Only one Epley Manoeuvre (EM) was performed on all patients. Based on the ipsilateral result of the EM, the contralateral result of the same EM and the BPPV resolution rate in the control group, a model was developed to predict the incidence of unilateral and bilateral BPPV in the SSG and the OSG. There were 234 patients in the control group, 20 in the SSG and 23 in the OSG. The model estimated that the percentage of unilateral BPPV would be 89.5% in SSG and 38.7% in OSG. Using these findings, we conclude that when both DHMs are positive, BPPV may be unilateral or bilateral. If the torsional components of both nystagmuses beat in the same sense, it is more likely to be unilateral BPPV. If the torsional components beat in opposite senses, both situations can be considered equally likely.Frequentemente nella pratica clinica si valutano pazienti che mostrano alle manovre di Dix-Hallpike (DHM), verso destra e verso sinistra, il nistagmo tipico della vertigine po - sizionale parossistica benigna (BPPV). In questi casi la BPPV può essere unilaterale o bilaterale. Lo scopo del presente studio è quello di descrivere l’incidenza della BPPV uni - laterale e bilaterale, quando entrambe le DHM sono positive, considerando il verso della componente torsionale del nistagmo. In questo studio prospettico multicentrico i pazienti sono stati suddivisi in tre gruppi: pazienti con solo una DHM positiva (gruppo di controllo, CG), pazienti con DHM positiva bilateralmente e con nistagmo battente nello stesso verso evocabile in entrambe le manovre (gruppo stesso verso, SSG), pazienti con DHM positiva bilateralmente e con nistagmo avente componente torsionale con verso opposto nelle due manovre (gruppo verso opposto, OSG). La manovra di Epley (EM) è stata condotta su tutti i pazienti. Considerando i risultati ottenuti dalla EM e il tasso di risoluzione della BPPV nel CG, è stato sviluppato un modello predittivo dell’incidenza della BPPV unilaterale e bilaterale negli SSG e OSG. Il CG comprendeva 234 pazienti, 20 erano inclusi invece nel SSG e 23 nell’OSG. Il modello ha stimato che la percentuale di BPPV unilaterale ammonterebbe a 89,5% nel SSG e 38,7% nel OSG. In conclusione, se entrambe le DHM sono positive, la BPPV può essere sia unilaterale che bilaterale. Se la componente torsionale dei nistagmi batte nello stesso verso, è più probabile che la BPPV sia unilaterale; se invece tale componente ha verso opposto alle DHM, le due condizioni possono considerarsi ugualmente probabili