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PubMed2006

Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder.

PURPOSE: The effect of bladder cancer histological subtypes other than transitional cell carcinoma (nonTCC) on clinical outcomes remains uncertain. We conducted a multi-institutional retrospective study of patients with bladder cancer treated with radical cystectomy to assess the impact of nonTCC histology on bladder cancer specific outcomes. MATERIALS AND METHODS: A total of 955 consecutive patients underwent radical cystectomy with bilateral pelvic lymphadenectomy for bladder cancer at 3 academic institutions. TCC was present in the radical cystectomy specimen in 888 patients (93%). NonTCC histology was present in 67 patients (7%), including squamous cell carcinoma in 26, adenocarcinoma in 13, small cell carcinoma in 10 and other nonTCC subtypes (ie spindle cell carcinoma, carcinosarcoma and undifferentiated carcinoma) in 18. For patients alive at last followup median followup was 39 and 23 months for patients with TCC and nonTCC histologies, respectively. Bladder cancer specific progression and survival were assessed using Kaplan-Meier and multivariate Cox proportional hazards analyses. RESULTS: Bladder cancer specific progression and mortality did not differ significantly between patients with SCC and TCC histologies. Patients with nonTCC and nonSCC bladder cancer were at significantly increased risk for progression and death compared to patients with TCC or SCC (p <0.001). This association remained statistically significant in patients with organ confined disease (stage pT2 or lower) and patients with nonorgan confined disease (stage pT3 or higher) (p <0.001). In a multivariate analysis nonTCC and nonSCC histology was associated with an increased risk of bladder cancer progression and death (OR 2.272 and 2.585, respectively, p <0.001), even after adjusting for final pathological stage, lymph node status, lymphovascular invasion and neoadjuvant or adjuvant treatments. CONCLUSIONS: NonTCC and nonSCC histological subtype is an independent predictor of bladder cancer progression and mortality in patients undergoing radical cystectomy for bladder cancer. Patients with bladder TCC and SCC share similar stage specific clinical outcomes.

Aged↗

PubMed1999

Detrimental subtype-specific endothelin-1 (ET-1) signaling in myocardial cells: the ET(A) mediated proliferation and ET(B)receptor down-regulation.

Many physiological and pathological processes in the cardiac tissue have been shown to be associated with a release of endothelin (ET) peptides and with induction of specific ET-receptors and G-protein-coupled ion channels. However, the exact mechanism regulating ET-receptors in the myocardium is controversial. The response to ET-1, the most important member of the ET family, is rapidly attenuated by down-regulation of ET-receptors. The internalization of ET-1 bound to two subclasses of specific receptors (ET(A) and ET(B)) that are abundant in the myocardium has been hypothesized to activate and/or inhibit a variety of intracellular signal transducing systems. The [125I]ET-1, BQ-3020 and selective ET-antagonists were used to study the subtype-selective component of regulation of ET-1 receptors in myocardial membranes. We determined the characteristics of [125I]ET-1 binding and [3H]thymidine incorporation in whole cell saturation studies and measured Ca2+ channel induction and the total number of inactive Ca2+ channels in photoaffinity studies with [3H]azidopine. Here we demonstrate four important components of the complex ET-1 response in human, porcine and rat myocardium, leading to aberrant responses of cells. After ET-1 induction, adaptive subtype-ETB selective down-regulation predominated in human embryonic fibroblasts, in porcine membrane vesicles and in microsomal membranes of renal hypertensive rats, with preferential high affinity ET-1 binding to ETA receptors and with the resultant ETA mediated proliferative and mitogenic activation of human fibroblasts. The ET-1 induction was also accompanied by profound inactivation of Ca2+ channels in myocardial membranes.

Animals↗

PubMed1992

Immunological detection of glutamate receptor subtypes in human central nervous system.

Glutamate receptors are the principal excitatory neurotransmitter receptors in the central nervous system and are involved in a number of normal and pathological neuronal processes. Using subunit-specific antipeptide antibodies developed against the predicted amino acid sequences of several rat glutamate receptor cDNAs, we have identified these proteins in post-mortem human central nervous system tissue. Immunoblotting of dissected brain regions demonstrates that these receptor proteins are differentially distributed. The ability to identify these proteins in post-mortem human tissues should allow examination of the changes in levels of receptor subtypes that occur in a variety of neurological and psychiatric diseases.

Adult↗

PubMed2005

Integrated array-comparative genomic hybridization and expression array profiles identify clinically relevant molecular subtypes of glioblastoma.

Glioblastoma, the most aggressive primary brain tumor in humans, exhibits a large degree of molecular heterogeneity. Understanding the molecular pathology of a tumor and its linkage to behavior is an important foundation for developing and evaluating approaches to clinical management. Here we integrate array-comparative genomic hybridization and array-based gene expression profiles to identify relationships between DNA copy number aberrations, gene expression alterations, and survival in 34 patients with glioblastoma. Unsupervised clustering on either profile resulted in similar groups of patients, and groups defined by either method were associated with survival. The high concordance between these separate molecular classifications suggested a strong association between alterations on the DNA and RNA levels. We therefore investigated relationships between DNA copy number and gene expression changes. Loss of chromosome 10, a predominant genetic change, was associated not only with changes in the expression of genes located on chromosome 10 but also with genome-wide differences in gene expression. We found that CHI3L1/YKL-40 was significantly associated with both chromosome 10 copy number loss and poorer survival. Immortalized human astrocytes stably transfected with CHI3L1/YKL-40 exhibited changes in gene expression similar to patterns observed in human tumors and conferred radioresistance and increased invasion in vitro. Taken together, the results indicate that integrating DNA and mRNA-based tumor profiles offers the potential for a clinically relevant classification more robust than either method alone and provides a basis for identifying genes important in glioma pathogenesis.

Adipokines↗

PubMed1999

Selective excitation of subtypes of neocortical interneurons by nicotinic receptors.

The cellular mechanisms by which neuronal nicotinic cholinergic receptors influence many aspects of physiology and pathology in the neocortex remain primarily unknown. Whole-cell recordings and single-cell reverse transcription (RT)-PCR were combined to analyze the effect of nicotinic receptor agonists on different types of neurons in acute slices of rat neocortex. Nicotinic receptor agonists had no effect on pyramidal neurons and on most types of interneurons, including parvalbumin-expressing fast spiking interneurons and somatostatin-expressing interneurons, but selectively excited a subpopulation of interneurons coexpressing the neuropeptides vasoactive intestinal peptide (VIP) and cholecystokinin. This excitation persisted in the presence of glutamate, GABA, and muscarinic receptor antagonists and in the presence of tetrodotoxin and low extracellular calcium, suggesting that the depolarization was mediated through the direct activation of postsynaptic nicotinic receptors. The responses were blocked by the nicotinic receptor antagonists dihydro-beta-erythroidine and mecamylamine and persisted in the presence of the alpha7 selective nicotinic receptor antagonist methyllycaconitine, suggesting that the involved nicotinic receptors lacked the alpha7 subunit. Single-cell RT-PCR analysis indicated that the majority of the interneurons that responded to nicotinic stimulation coexpressed the alpha4, alpha5, and beta2 nicotinic receptor subunits. Therefore, these results provide a role for non-alpha7 nicotinic receptors in the selective excitation of a subpopulation of neocortical interneurons. Because the neocortical interneurons expressing VIP have been proposed previously to regulate regional cortical blood flow and metabolism, these results also provide a cellular basis for the neuronal regulation of cortical blood flow mediated by acetylcholine.

Acetylcholine↗

PubMed1990

Clinical applications of the pathological properties of small cell carcinoma, large cell carcinoma, and adenoid cystic carcinoma of the lung.

Lung cancer has considerable treatment problems, with a poor 5-yr survival rate after surgery. Application of histopathological and immunohistopathological subtyping have proven to be powerful tools for the assessment of prognosis. Results in 33 patients with small cell carcinoma, 44 with large cell carcinoma, and five with adenoid cystic carcinoma of the lung are discussed. The 5-yr survival rates in patients with small cell carcinoma of the oat cell type and intermediate type were 24 and 44%, respectively. Argyrophilic granules and neuron-specific enolase, neuroendocrine markers, were detected more frequently in the oat cell type rather than in the intermediate type. In contrast, keratin, epithelial membrane antigen, and carcinoembryonic antigen, epithelial origin markers, were present more frequently in the intermediate type than in the oat cell type. The 5-yr survival rates with large cell carcinoma of the compact growth type and the loose structure type were 46 and 28%, respectively, based on evidence of morphologically intercellular cohesion. The epithelial origin markers were detectable and more frequent in the compact growth type than in the loose structure type. The growth patterns of adenoid cystic carcinoma are classified as tubular, cribriform, and solid. The solid pattern was the most aggressive with extensive perineural invasion. We propose that the pathological properties of lung cancer should be examined as a prognostic implication of subtyping.

Adult↗

PubMed2002

Prostanoid receptor subtypes.

Prostanoids are a group of lipid mediators that include the prostaglandins (PG) and thromboxanes (TX). Upon cell stimulation, prostanoids are synthesized from arachidonic acid via the cyclooxygenase (COX) pathway and released outside the cells to exert various physiological and pathological actions in a variety of tissues and cells. The activities of prostanoids are mediated by specific G protein-coupled receptors, which have been classified on the basis of pharmacological experiments into eight types and subtypes according to their responsiveness to selective agonists and antagonists. These prostanoid receptors have been cloned from various species including human, and their distinct binding properties and signal transduction pathways have been characterized by analyses of cells expressing each receptor. Furthermore, the distribution patterns of prostanoid receptor mRNAs have been determined in tissues and cells for various species. This information is useful for understanding the molecular basis of the pathophysiological actions of prostanoids.

Animals↗

PubMed1995

Discovery of losartan, the first angiotensin II receptor antagonist.

The 'discovery' of losartan represents three separate discoveries: (1) losartan as the unique biphenyltetrazole molecule and the first of a new chemical class; (2) losartan as a tool to identify AT1-subtype receptors; and (3) losartan as a specific probe for exploring the multiple roles of angiotensin II (Ang II) in normal physiology and pathologic states. Losartan is the first nonpeptide orally active Ang II receptor antagonist to reach clinical trials. Losartan was selected for its affinity for Ang II receptors, functional antagonism of Ang II, lack of agonist properties, and oral anti-hypertensive effects. Losartan has been widely used to define the distribution and function of AT receptor subtypes. Although possible roles of the AT2 subtype have been reported, virtually all of the known effects of Ang II are blocked by losartan. Specific AT1 receptor blockade has been broadly compared with ACE inhibition. Possible differences on the basis of AT1 selectivity, bradykinin potentiating effects and Ang II formed by non-ACE pathways are discussed. Losartan blocks the vascular constrictor effect of Ang II, the Ang II-induced aldosterone synthesis and/or release, and the Ang II-induced cardiovascular 'growth' in vitro and in vivo. In various models of experimental hypertension, losartan prevents or reverses the elevated blood pressure and the associated cardiovascular hypertrophy similar to ACE inhibitors. Likewise, in models of renal failure (for example reduced renal mass, puromycin, ochratoxin), losartan, like ACE inhibition, markedly reduced the elevation in blood pressure, proteinuria or sclerosis. In aortocaval shunt, coronary ligation and ventricular pacing models of heart failure, losartan demonstrated a pathological role for Ang II by reversing the associated haemodynamic findings. In SHR-stroke prone, losartan dramatically increased survival while having a limited effect on blood pressure, suggesting a non-pressure dependent effect of Ang II. These collective data show that Ang II exerts complex pathological effects in experimental models of vascular, cardiac, renal and cerebral disease. The effectiveness of losartan in experimental models of heart failure supports its evaluation in clinical trials with patients with heart failure.

Angiotensin II↗

PubMed1994

Alpha 2-adrenoceptors: more subtypes but fewer functional differences.

The proliferation of receptor subtypes based on differences in amino acid sequence does not necessarily coincide with functional differences. The number of alpha 2-adrenoceptor subtypes, as defined by ligand-binding and molecular studies, has been increasing in the past few years, which suggests the possibility of distinct physiological and pathological pathways that could be targeted by new selective drugs. However, the evidence from functional studies has been less convincing. This could be due to the lack of sufficiently selective ligands or to the similarity between the activated state of receptor subtypes. Species differences and the local receptor environment are also important determinants of the pharmacological profile of a particular subtype. The pharmacology of the putative subtypes of alpha 2-adrenoceptors and their function are discussed in this review by Alison MacKinnon, Mike Spedding and Christine Brown.

Adrenergic alpha-Antagonists↗

PubMed2004

Getting closer to affective disorders: the role of CRH receptor systems.

Depressive disorders are a leading cause of morbidity and mortality worldwide. Current antidepressant drugs targeting monoamine neurotransmitter systems have a delayed onset of action, and fewer than 50% of the patients attain complete remission after therapy with a single antidepressant. A large body of preclinical and clinical evidence points to a key role of the corticotropin-releasing hormone (CRH) receptor 1 subtype (CRHR1) in mediating CRH-elicited effects in anxiety, depressive disorders and stress-associated pathologies. Genetic modification of CRHR1 function in mice by the use of conventional and conditional knockout strategies enables further analysis of specific elements in the CRH circuitry. The recent characterisation of several selective small-molecule CRHR1 antagonists offers new possibilities for the treatment of anxiety and depression.

Animals↗

PubMed2002

The rationale behind cholinergic drug treatment for dementia related to cerebrovascular disease.

Common to all subtypes of dementia, including Alzheimer's disease (AD), and those associated cerebrovascular disease (CVD), Lewy body pathology and Parkinson's disease, is degeneration of cholinergic neurotransmission. The cholinergic hypothesis of AD is based on evidence of reduced cholinergic markers and decreased numbers of cholinergic neurons and nicotinic acetylcholine receptors (nAChR) in the hippocampus and cortex of the brain-both areas associated with memory, learning and executive function impairments characteristic of cognitive decline in AD. There is growing evidence for the involvement of the cholinergic system in vascular dementia (VaD). Attention has, therefore, recently turned to the use of cholinergic treatments such as galantamine (Reminyl), which has demonstrated broad-spectrum and long-term efficacy in AD, for the treatment of patients with VaD or AD with CVD. Galantamine is both a moderate, reversible, competitive acetylcholinesterase inhibitor, and an allosteric modulator of nAChR. Recent evidence suggests that the unmatched efficacy of galantamine in cognitive as well as behavioral and functional symptoms in patients with AD, as well as those with VaD or AD with CVD, may at least partly result from its unique dual cholinergic mode of action. Here, the rationale for using galantamine to treat dementia related to CVD is discussed. In particular, some interesting findings are covered which indicate the potential of galantamine to modulate other neurotransmitter systems (e.g. serotonergic, dopaminergic), which may be of specific relevance in the behavioral symptoms of dementia related to CVD.

Aged↗

PubMed1997

Changes in CSF spaces differ in endogenous and neurotic depression. A planimetric CT scan study.

Regional planimetric measurements of internal and external CSF spaces were performed in CT scans of 23 patients with endogenous depression (ICD 9, 296.1) and 28 patients with neurotic depression (ICD 9, 300.4) as compared to 56 control individuals without neuropsychiatric disorder. In female patients with endogenous depression, but not in men, the bilateral upper cortical sulci were widened, especially in the frontal regions, and the third ventricle was enlarged. In contrast, the female neurotic depressed group showed no enlargement of CSF spaces, but a narrowing of the Sylvian fissure and of the basal frontal lobe reaching level of significance in the right fronto-temporal region (P = 0.005). No narrowing of CSF spaces was observed in women with endogenous depression. A discriminant analysis of significantly changed CSF regions resulted in a correct classification in 82.4% of depressed women in either the endogenous or the neurotic group. Determination of divergent types of brain pathology might prove as a useful tool in validating the differential classification of these two main subtypes of affective disorders.

Adult↗

PubMed2003

Tricyclic pyrazoles. Part 1: synthesis and biological evaluation of novel 1,4-dihydroindeno[1,2-c]pyrazol-based ligands for CB1and CB2 cannabinoid receptors.

Cannabinoids receptors, cellular elements of the endocannabinoid system, have been the focus of extensive studies because of their potential functional role in several important physiological and pathological processes. To further evaluate the properties of CB receptors, especially CB(1) and CB(2) subtypes, we have designed, using SR141716A as a benchmark, a new series of rigid 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides. Compounds 1 were synthesized from substituted 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxylic acids and requisite amines. The various analogues were assayed for binding both to the brain and peripheral cannabinoid receptors (CB(1) and CB(2)). Seven of the new compounds displayed very high in vitro CB(2) binding affinities, especially 1a, 1b, 1c, 1e, 1g, 1h and 1j which showed K(i) values of 0.34, 0.225, 0.27, 0.23, 0.385, 0.037 and 0.9 nM, respectively. Compounds 1a, 1b, 1c and 1h showed the highest selectivity for CB(2) receptor with K(i)(CB(1)) to K(i)(CB(2)) ratios of 6029, 5635, 5814 and 9810, respectively. Noticeably, 1h exhibited the highest affinity and selectivity for CB(2) receptors.

Amines↗

PubMedDate not supplied

Cytosolic phospholipase A2: biochemical properties and physiological roles.

Phosphatidylcholine (PC) is a major constituent of biological membranes and a component of serum lipoproteins and pulmonary surfactants. The PC and other glycerophospholipid compositions of membranes change dynamically through stimulus-dependent and independent pathways, principally by the action of two different types of enzymes; phospholipase A2 [EC 3.1.1.4] and acyl-CoA:lysophospholipid acyltransferase [EC 2.3.1.23]. Phospholipase A2 is a key enzyme that catalyzes deacylation of the sn-2 position of glycerophospholipids. This enzyme is critical in the remodeling of membrane lipids and formation of two subclasses of lipid mediators, fatty acid derivatives and lysophospholipids. Among many different subtypes of phospholipase A2 enzymes, we found that cytosolic phospholipase A2alpha (cPLA2alpha) is important in various pathological and physiological responses. Here, we summarize the phenotypes resulting from genetic ablation of cPLA2alpha, and the properties of newly discovered enzymes in the cPLA2 family. Comprehensive analysis of lipid mediators using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is useful for understanding the roles of individual mediators in physiological and pathological processes.

Animals↗

PubMed2000

Genetic alterations in chronic ulcerative colitis-associated adenoma-like DALMs are similar to non-colitic sporadic adenomas.

Recent molecular studies have shown that there are differences in the prevalence and timing of certain molecular events between chronic ulcerative colitis (CUC)-associated dysplastic lesions and non-CUC-related sporadic adenomas. However, little is known regarding the molecular features of a specific subtype of CUC-related dysplasia-associated lesion or mass (DALM) that clinically, endoscopically, and pathologically resemble sporadic adenomas, and whether these lesions can be separated from non-CUC-related sporadic adenomas on the basis of their molecular genotype. Therefore, the purpose of this study was to evaluate loss of heterozygosity (LOH) of 3p, APC, and p16 in a specific group of CUC-associated "adenoma-like" DALMs and to compare the results of this tumor with those in a well-defined group of CUC-associated non-adenoma-like DALMs and non-CUC-associated sporadic adenomas. Polypectomy or resection specimens from 21 CUC patients with an adenoma-like DALM, 8 CUC patients with at least one nonadenoma-like DALM (12 lesions in total), and 23 non-CUC patients with a sporadic adenoma were evaluated for LOH of 3p, APC, and p16 by PCR analysis. The results were compared among the three different study groups and correlated with the clinical features of the patients and the pathology of their tumors. Chronic ulcerative colitis-associated adenoma-like DALMs showed LOH of 3p in five of 18 (28%) cases. This value was not significantly different from the 5% of non-CUC sporadic adenomas (p = 0.14) that were positive. However, 50% of CUC-associated non-adenoma-like DALMs were positive for LOH of 3p, and this value was significantly higher (p = 0.01) than the other groups. The frequency of LOH of APC did not differ significantly between the three patient groups (33%, 33%, and 43% in the three groups, respectively). Similar to the 3p results, CUC-associated adenoma-like DALMs and non-CUC-associated sporadic adenomas showed a similar low frequency of positivity for LOH of p16 (5% and 4%, respectively) in comparison to 56% of CUC-associated non-adenoma-like DALMs (p = 0.003). For all markers, no significant differences were detected in the CUC-associated adenoma-like DALM group between lesions that occurred within colitis compared with those that occurred in areas not involved by colitis. Chronic ulcerative colitis-associated non-adenoma-like DALMs have a different molecular genotype than CUC-related adenoma-like DALMs and non-CUC sporadic adenomas. Our data also suggests that the latter two groups of neoplasms may in fact represent a similar, if not identical, pathogenetic entity.

Adenomatous Polyps↗

PubMed2001

Aggression and psychiatric comorbidity in children with hypothalamic hamartomas and their unaffected siblings.

OBJECTIVE: To assess aggression and psychiatric comorbidity in a sample of children with hypothalamic hamartomas and gelastic seizures and to assess psychiatric diagnoses in siblings of study subjects. METHOD: Children with a clinical history of gelastic seizures and hypothalamic hamartomas (n = 12; age range 3-14 years) had diagnoses confirmed by video-EEG and head magnetic resonance imaging. Structured interviews were administered, including the Diagnostic Interview for Children and Adolescents-Revised Parent Form (DICA-R-P), the Test of Broad Cognitive Abilities, and the Vitiello Aggression Scale. Parents were interviewed with the DICA-R-P about each subject and a sibling closest in age without seizures and hypothalamic hamartomas. Patients were seen from 1998 to 2000. RESULTS: Children with gelastic seizures and hypothalamic hamartomas displayed a statistically significant increase in comorbid psychiatric conditions, including oppositional defiant disorder (83.3%) and attention-deficit/hyperactivity disorder (75%). They also exhibited high rates of conduct disorder (33.3%), speech retardation/learning impairment (33.3%), and anxiety and mood disorders (16.7%). Significant rates of aggression were noted, with 58% of the seizure patients meeting criteria for the affective subtype of aggression and 30.5% having the predatory aggression subtype. Affective aggression was significantly more common (p < .05). Unaffected siblings demonstrated low rates of psychiatric pathology on semistructured parental interview and no aggression as measured by the Vitiello Aggression Scale. CONCLUSIONS: Children with hypothalamic hamartomas and gelastic seizures had high rates of psychiatric comorbidity and aggression. Parents reported that healthy siblings had very low rates of psychiatric pathology and aggression.

Adolescent↗

PubMed2005

Prognostic factors in localized invasive cutaneous melanoma: high value of mitotic rate, vascular invasion and microscopic satellitosis.

The aim of this study was to determine independent clinical and pathological prognostic factors for overall and disease-free survival in Spanish melanoma patients. Eight hundred and twenty-three patients with localized melanoma and complete clinical and pathological information were evaluated. The age at diagnosis, gender, location, tumour thickness, invasion level, ulceration, histological subtype, inflammatory infiltrate, mitotic rate, vascular invasion, microscopic satellitosis, regression and cell type were all included. Univariate and multivariate Cox regression analyses were performed for overall and disease-free survival. Gender, histological subtype, tumour thickness, invasion level, ulceration, inflammatory infiltrate, microscopic satellitosis, vascular invasion and mitotic rate were related to overall and disease-free survival in univariate analysis. Age and location were only related to disease-free survival. Only tumour thickness, vascular invasion and gender exhibited independent significance for overall survival in multivariate analysis. For disease-free survival, tumour thickness, location, mitotic rate, vascular invasion and microscopic satellitosis were the sole independent factors. It can be concluded that the Breslow thickness remains the most significant prognostic factor for the survival of patients with localized cutaneous melanoma. Our results support the inclusion of microscopic satellitosis and vascular invasion in the current American Joint Committee on Cancer (AJCC) staging system, although further studies evaluating their separate influence are needed. Mitotic rate is confirmed as an objective and independent predictor of disease-free survival for melanoma patients that should be considered in further revisions of the mentioned staging system.

Adolescent↗

PubMed1994

Heterogeneity in B-cell neoplasms associated with rearrangement of the LAZ3 gene on chromosome band 3q27.

The LAZ3 gene has been identified on chromosome band 3q27, which is the breakpoint of reciprocal chromosome translocations observed in B-cell non-Hodgkin's lymphoma (NHL). Although the translocations affect various chromosome sites including the immunoglobulin gene loci, molecular studies have indicated that the breakages are clustered within a 10-kb-long major translocation cluster region (MTC) at band 3q27. In the current study, we have used a genomic probe from the MTC to study 51 Japanese patients having B-cell neoplasms with regard to rearrangement of LAZ3. The study detected rearrangement in 12 cases out of 51; the rearrangements occurred within a limited region close to the first exon of the LAZ3 gene. Eight cases out of 12 with rearrangement had diffuse large cell NHL and the immunoblastic variant, including one case transformed from a follicular lymphoma carrying the BCL2 rearrangement. However, the rearrangement was also identified in two NHL patients showing a follicular growth pattern, in one case with indolent chronic lymphocytic leukemia and in one case with high-grade small noncleaved cell lymphoma with a bulky abdominal mass. Cytogenetic analysis revealed t(3;14)(q27;q32) in 2 cases, t(3;22)(q27;q11) in 3, and a newly identified translocation t(3;6)(q21) in one case. LAZ3 expression was demonstrated in cells carrying the LAZ3 rearrangement, suggesting transcriptional deregulation of the gene. Our results are compatible with previous cytogenetic reports in which the 3q27 translocation was observed in 15-20% of NHL; however, patients with the LAZ3 rearrangements exhibited a wide range of clinico-pathologic characteristics. Thus, there is no clear consistent association of the 3q27 translocation with a specific subtype of B-cell neoplasm.

Adult↗