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PubMed2006

Targeting PGE2 receptor subtypes rather than cyclooxygenases: a bridge over troubled water?

Prostaglandins (PG) are synthesized by the sequential action of phosholipases, cyclooxygenases (COX)-1 and COX-2, and specific terminal synthases, and exert their diverse biological effects through several membrane receptors. In particular, PGE2 is involved in many normal and pathological pathways that are mediated by four different E prostanoid receptors (EP1-4). Selective COX-2 inhibitors (Coxibs) have analgesic and antipyretic effects that are indistinguishable from those of nonsteroidal anti-inflammatory drugs (NSAIDs), but some possess hazardous cardiovascular side effects. Recent results indicate that EP1 and EP4 antagonists might prove useful for inhibiting the unwanted actions of COX-2. Has the time come for research to examine earnestly the selective antagonism of EP subtypes rather than further the development of direct COX-2 inhibitors?

Animals↗

PubMed1997

Biopsychosocial profile of women with dyspareunia.

OBJECTIVE: To compare biopsychologic profiles of women with dyspareunia with a matched no-pain control sample, and to determine whether dyspareunia subtypes based on physical findings have different psychosocial profiles from matched controls. METHODS: One hundred and five women with dyspareunia and 105 matched no-pain control women underwent standard gynecologic examination, endovaginal ultrasound, and colposcopy. They also completed a structured interview inquiring about pain other than dyspareunia, sexual function, and history of abuse, the Brief Symptom Inventory, the Sexual Opinion Survey, and the Locke-Wallace Marital Adjustment Scale. RESULTS: In comparison with women who do not experience pain with intercourse, the dyspareunia sample was found to have more physical pathology on examination, and they reported more psychologic symptomatology, more negative attitudes toward sexuality, higher levels of impairment in sexual function, and lower levels of marital adjustment. They did not report more current or past physical or sexual abuse. However, when the undifferentiated dyspareunia sample was divided into subtypes based on physical findings from the gynecologic examinations, the pattern of significant differences from controls varied according to dyspareunia subtype. Elevated psychologic symptomatology and relationship maladjustment were confined to the subtype with no discernible physical findings who reported levels of sexual function not significantly different from matched controls. The vulvar vestibulitis subtype suffered the highest levels of sexual impairment, although this subtype was not characterized by higher levels of psychologic symptoms than controls. CONCLUSION: As an undifferentiated group, women with dyspareunia have more physical pathology, psychologic distress, sexual dysfunction, and relationship problems. However, this pattern of differences appears to vary depending on the presence and type of physical findings evident on examination. Dyspareunia is a heterogeneous disorder requiring comprehensive gynecologic and psychosocial assessment to determine differentiated treatment strategies.

Adult↗

PubMedDate not supplied

Trends of prevalence and pathological spectrum of head and neck cancers in North India.

BACKGROUND: Head and neck neoplasia constitute one of the commonest cancers in India. Use of smokeless tobacco (Pan masala, Zarda etc.) is on the increase in North India, especially in Uttar Pradesh, and is responsible for the large majority of these tumours. AIM: To assess the patients' characteristics, yearly prevalence and histopathological subtypes of the head and neck neoplasia (excluding oral cavity) in Allahabad and surrounding regions. SETTINGS AND DESIGN: A retrospective study of 11 years from 1990 to 2000 was designed. Data was collected year-wise using the tumor registry data. MATERIAL AND METHODS: All biopsies submitted for histopathology to the Pathology department were reviewed and analyzed for demographic data, site and diagnosis. STATISTICAL ANALYSIS: The Kolmogorov-Smirnov Two-Sample Test was utilized to determine whether two distributions are the same. RESULTS: A total of 40559 biopsies were examined in the department, of which, lesions of the head and neck region, excluding the oral cavity, constituted 694 biopsies (409 males and 285 females). One hundred and forty-four malignant lesions were reported, 114 being males and 30 females. A comparison of the age-specific prevalence rates of cancer during the study period showed that the prevalence was highest in patients belonging to the 50-59 years age group and squamous cell carcinoma Grade II was the most prevalent type. On an average, 58 new biopsies per annum were received. CONCLUSIONS: Properly structured site-specific data like this can augment the National Cancer Registry Programme and is an essential indicator for the magnitude and the pattern of the cancer problem in India.

Adolescent↗

PubMed1998

An MRI and MRS study of Pelizaeus-Merzbacher disease.

Earlier reports on T2-weighted magnetic resonance imaging (MRI) in the classical form of Pelizaeus-Merzbacher disease seemed to divide the patterns of the high-intensity lesions in the white matter into three subtypes: type I, diffusely hemispheric and corticospinal; type II, diffusely hemispheric without brainstem lesions; and type III, patchy in the hemispheres. The four boys presented in our study, between 10 and 17 years of age, with classical Pelizaeus-Merzbacher disease, who all had a duplicated proteolipid protein gene, invariably manifested type I despite their various clinical severities. Follow-up MRI after an interval of 5 years and proton magnetic resonance spectroscopy was performed in three of the patients. The white matter on the last MRI was unchanged in volume and the distribution of high-intense areas. Proton magnetic resonance spectroscopy revealed no abnormal peaks. These results were consistent with the lack of definite neurologic regression in the last 5 years and with the pathologic characteristics of well-preserved axons and the absence of sclerosis. Further study is required to precisely determine whether the patterns of MRI findings can be divided into subtypes corresponding to those of proteolipid protein gene abnormalities.

Adolescent↗

PubMed1996

Breast lymphoma--a pathologic study of 14 cases.

Fourteen cases of malignant non-Hodgkin's lymphoma of the breast were diagnosed at the Department of Pathology, Singapore General Hospital, since 1988. All were females with an age range of 30 to 69 years. Twelve cases were B cell and 2 were T cell in immunophenotype. Of the B cell lymphomas, one was subtyped as follicular, 8 diffuse large cell (IWF) or centroblastic (Kiel) and 3 immunoblastic lymphomas. Both T cell tumours were Ki-1 positive, large cell anaplastic lymphomas. Malignant lymphoma was not clinically suspected in any patient at presentation. Histologically, 3 cases were initially diagnosed as carcinomas, one on a trucut biopsy, another during frozen section evaluation and the third was a breast excision specimen. The pathological characteristics and potential histologic problems are detailed. The rarity of the disease, lack of uniform classification and variable treatment modalities make prognostic predictions of breast lymphoma difficult.

Adult↗

PubMed2000

Neuronal nicotinic receptors in the human brain.

Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of ligand gated ion channels which are widely distributed in the human brain. Multiple subtypes of these receptors exist, each with individual pharmacological and functional profiles. They mediate the effects of nicotine, a widely used drug of abuse, are involved in a number of physiological and behavioural processes and are additionally implicated in a number of pathological conditions such as Alzheimer's disease, Parkinson's disease and schizophrenia. The nAChRs have a pentameric structure composed of five membrane spanning subunits, of which nine different types have thus far been identified and cloned. The multiple subunits identified provide the basis for the heterogeneity of structure and function observed in the nAChR subtypes and are responsible for the individual characteristics of each. A substantial amount of information on human nAChR structure and function has come from studies on neuroblastoma cell lines which naturally express nAChRs and from recombinant nAChRs expressed in Xenopus oocytes. In vitro brain nAChR distribution can be mapped with a number of appropriate agonist and antagonist radioligands and subunit distribution may be mapped by in situ hybridization using subunit specific mRNA probes. Receptor distribution in the living human brain can be studied with noninvasive imaging techniques such as PET and SPECT, with a significant reduction in nAChRs in the brains of Alzheimer's patients having been identified with [11C] nicotine in PET studies. Despite the significant body of knowledge now accumulated about nAChRs, much remains to be elucidated. This review will attempt to describe the current knowledge on the nAChR subtypes in the human brain, their functional roles and neuropathological involvement.

Animals↗

PubMed2001

Nicotinic receptor abnormalities of Alzheimer's disease: therapeutic implications.

The neuronal nicotinic acetylcholine receptors (nAChRs) in the brain are important for functional processes, including cognitive and memory functions. The nAChRs acting as neuromodulators in communicative processes regulated by different neurotransmitters show a relatively high abundance in the human cortex, with a laminar distribution of the nAChRs of superhigh, high, and low affinity in the human cortex. The regional pattern of messenger RNA (mRNA) for various nAChR subtypes does not strictly follow the regional distribution of nAChR ligand-binding sites in the human brain. Consistent losses of nAChRs have been measured in vitro in autopsy brain tissue of Alzheimer's disease patients (AD), as well as in vivo by positron emission tomography (PET). Measurement of the protein content of nAChRs showed reduced levels of the alpha4, alpha3, and alpha7 nAChR subtypes. The finding that the alpha4 and alpha3 mRNA levels were not changed in AD brains suggests that the losses in high-affinity nicotinic-binding sites cannot be attributed to alterations at the transcriptional level of the alpha4 and alpha3 genes and that the causes have to be searched for at the translational and/or posttranslational level. The increased mRNA level of the alpha7 nAChR subtyep in the hippocampus indicates that subunit-specific changes in gene expression of the alpha7 nAChR might be associated with AD. The PET studies reveal deficits in nAChRs as an early phenomena in AD, stressing the importance of nAChRs as a potential target for drug intervention. PET ligands measuring the alpha4 nAChRs are under development. Studies of the influence of beta-amyloid on nAChRs in brain autopsy tissue from patients with the amyloid precursor protein 670/671 mutation have shown that there is no direct relationship between nAChR deficits and pathology. Treatment with cholinergic drugs in AD patients indicate improvement of the nAChRs in the brain, as visualized by PET. Further studies on neuroprotective mechanisms mediated via nAChR subtypes are exciting new avenues.

Aged↗

PubMed2004

Molecular and clinicopathologic comparisons of head and neck squamous carcinoma variants: common and distinctive features of biological significance.

To investigate, for the first time, the events associated with the phenotypic and clinical diversities of head and neck squamous carcinomas (HNSC), we performed molecular analyses on 92 primary tumors representing the entire spectrum of the morphologic subtypes using microsatellite markers at chromosome 3p, 4p, 8p, 9p, 11q, 17p, and 18q regions and correlated the results with the clinicopathologic features and patients' survival. Loss of heterozygosity (LOH) at D9S168 and D9S171 markers on chromosome 9p regions was commonly identified in all subtypes. Distinctive alterations in certain subtypes were noted at chromosomes 3p, 4p, 8p, and 11p regions. In general, less aggressive types (verrucous, papillary, and well-differentiated conventional) had a significantly lower LOH incidence than the more aggressive (basaloid, sarcomatoid, and high-grade conventional squamous carcinoma) categories. Significant association between LOH and age, stage, nodal status, and patient outcome was found. Survival analysis revealed that pathologic categorization (less versus more aggressive) and LOH at marker D11S4167 and D3S2432 are independent predictors of patients' survival. Our analysis also defined a set of limited markers that account for most of alterations within and across these tumor subtypes. Our study indicates that 1) certain genetic markers are common to all subtypes of HNSC supporting their early involvement in tumorigenesis, 2) inter- and intratumoral genetic differences evolve subsequently and may underlie their morphologic heterogeneity, 3) high incidence of LOH in certain regions characterizes aggressive tumors, 4) categorical classification and LOH at 11p and 3p regions independently correlated with patient survival, and 5) a limited set of markers identify the majority of genetic alterations in these tumors.

Adult↗

PubMed2004

Pathology of upper gastrointestinal malignancies.

This review describes the most important macroscopic, histological, and molecular biological features of carcinomas of the esophagus, the gastroesophageal junction (GEJ), and the stomach. The three most frequent histological subtypes of upper GI tract carcinoma, ie, adenocarcinoma, squamous cell carcinoma, and small cell carcinoma, are considered. Important histological classifications of upper GI tract adenocarcinomas such as Lauren's classification and the World Health Organization (WHO) classification, as well as rare histological variants of esophageal and gastric cancer, are described. Routes of tumor spread and principles of tumor classification are outlined. Furthermore, descriptions of the immediate precursor lesions of upper GI tract carcinomas, ie, dysplasias, are included. Finally, somatic genetic and epigenetic changes, which are associated with tumor development in the upper GI tract, are discussed.

Adenocarcinoma↗

PubMedDate not supplied

[Pathology of soft tissue sarcomas: 238 cases of the childhood tumor registry].

Until April 1981 malignant soft tissue sarcomas were registered from 238 patients. Rhabdomyosarcoma was the most common tumor (115/238 = 48.3%). The embryonal subtype was predominantly seen among the rhabdomyosarcomas (83/115 = 72.2%). Rhabdomyosarcomas were localized most frequently in the head and neck area (40/115 = 34.8%), followed by genitourinary system (15/115), pelvis soft tissue (12), abdomen (10) and extremities (10). Non-rhabdomyosarcomatous soft tissue sarcomas (123/238 = 51.7%) were synovial sarcomas (20 = 8.4%), fibrosarcomas including spindle cell sarcoma (17 = 7.4%), leiomyosarcomas (12 = 5.0%), malignant tumors of the vascular system (11 = 4.6%) and neurofibrosarcomas (9 = 3.8%). Other types of sarcoma were extremely rare. 42 (17.6%) of all soft tissue sarcomas could not be classified histogenetically. Rhabdomyosarcomas could be diagnosed much more accurately (105/115 = 91.3%), compared to all other soft tissue sarcomas (99/121 = 81.8%). At present, the most difficult diagnostic problems remain with the tumors of connective tissue, in particular with fibrosarcomas and with the differential diagnosis of juvenile fibrosarcomas versus juvenile fibromatoses.

Adolescent↗

PubMed1981

The Rye classification of a population based series of Hodgkin's disease patients in Western Australia.

Data are presented on the incidence in Western Australia of subtypes of Hodgkin's disease which were obtained by review of all cases of the disease notified between 1960 and 1974. Observations were also made on within- and between-observer agreement on the use of the Rye classification by a group of 9 surgical pathologists, all in the day-to-day practice of pathology. Although many consensus diagnoses were made only after spirited discussion by the Group, the results suggested that general surgical pathologists can perform nearly as well as lymphoma experts. A comparison of the incidence of Hodgkin's disease and distribution of Rye subtypes in Western Australia with 4 other populations showed a similar overall incidence but appreciable variation in the relative frequency of the subtypes--mainly in the proportions of nodular sclerosing and mixed cellularity.

Adolescent↗

PubMed2001

Regulation of thyroid hormone receptor isoforms in physiological and pathological cardiac hypertrophy.

Physiological and pathological cardiac hypertrophy have directionally opposite changes in transcription of thyroid hormone (TH)-responsive genes, including alpha- and beta-myosin heavy chain (MyHC) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), and TH treatment can reverse molecular and functional abnormalities in pathological hypertrophy, such as pressure overload. These findings suggest relative hypothyroidism in pathological hypertrophy, but serum levels of TH are usually normal. We studied the regulation of TH receptors (TRs) beta1, alpha1, and alpha2 in pathological and physiological rat cardiac hypertrophy models with hypothyroid- and hyperthyroid-like changes in the TH target genes, alpha- and beta-MyHC and SERCA. All 3 TR subtypes in myocytes were downregulated in 2 hypertrophy models with a hypothyroid-like mRNA phenotype, phenylephrine in culture and pressure overload in vivo. Myocyte TRbeta1 was upregulated in models with a hyperthyroid-like phenotype, TH (triiodothyronine, T3), in culture and exercise in vivo. In myocyte culture, TR overexpression, or excess T3, reversed the effects of phenylephrine on TH-responsive mRNAs and promoters. In addition, TR cotransfection and treatment with the TRbeta1-selective agonist GC-1 suggested different functional coupling of the TR isoforms, TRbeta1 to transcription of beta-MyHC, SERCA, and TRbeta1, and TRalpha1 to alpha-MyHC transcription and increased myocyte size. We conclude that TR isoforms have distinct regulation and function in rat cardiac myocytes. Changes in myocyte TR levels can explain in part the characteristic molecular phenotypes in physiological and pathological cardiac hypertrophy.

Animals↗

PubMed1986

Parkinson's disease: nigral receptor changes support peptidergic role in nigrostriatal modulation.

Autoradiographic studies reveal densities of binding to somatostatin, neurotensin, mu-opiate, and benzodiazepine receptors in substantia nigra specimens from neurologically normal human brains. Binding to nigral angiotensin converting enzyme is also dense, whereas more modest densities of kappa-opiate, dopamine, and serotonin receptors are noted. In nigral specimens taken from patients with idiopathic Parkinson's disease, substantial reductions in somatostatin, neurotensin, mu-opiate and kappa-opiate receptors contrast with more modest reductions in dopamine and benzodiazepine I receptor subtypes. Angiotensin converting enzyme, serotonin, and benzodiazepine II binding are virtually unaltered. These results underscore the likelihood of strong peptidergic influences on normal and pathologically altered human nigrostriatal circuitry.

Adult↗

PubMed1987

Unexpected reading precocity in a normal preschooler: implications for hyperlexia.

This is a case study of a left-handed, preschool boy of superior intelligence who read very early and at a level well beyond what his IQ would predict. He is developmentally normal with no signs of autism or related disorders. His reading age was 9.3 at age 2-11 and 11.2 at 4-2; these levels are considerably beyond what would be predicted by his IQ or language age. He was able to read nonwords and both regular and irregular words equally well, indicating his mechanisms of lexical access in reading are similar to those of normal readers. Unlike classical hyperlexics, his reading comprehension for both single words and sentences was well above age level. When his precocious reading first appeared, he was also advanced in reading-related linguistic skills, such as phoneme awareness, auditory verbal short-term memory, and word retrieval, but not in visuospatial skills. These results imply that neither pathological language and/or social development, nor pathological variation in the normal mechanisms of lexical access in reading are necessary causes for reading precocity in early childhood. A model for integrating subtypes of precocious readers with subtypes of normal and dyslexic readers is proposed.

Child, Gifted↗

PubMed2006

Changes in CB1 receptors in motor-related brain structures of chronic relapsing experimental allergic encephalomyelitis mice.

Recent studies have examined the changes in the activity of cannabinoid signaling system in multiple sclerosis (MS), as a way to explain the efficacy of cannabinoid compounds to alleviate spasticity, pain, tremor and other signs of this autoimmune disease. In the present study, we have further explored this issue by examining density, mRNA expression and activation of GTP-binding proteins for the cannabinoid CB1 receptor subtype in several brain structures of mice with chronic relapsing experimental allergic encephalomyelitis (CREAE), a chronic model of MS that reproduces many of the pathological hallmarks of the human disease. CREAE animals were used at different phases in the progression of the disease (acute, remission and chronic) and compared to control mice. We observed several changes in the status of CB1 receptors that were region-specific and mainly circumscribed to motor-related regions, which is compatible with the symptomatology described for these animals that is preferentially of motor nature. We found a moderate decrease in the density of CB1 receptors in the caudate-putamen during the acute phase of CREAE. These reductions disappeared during the remission phase, but they were again observed, to a more marked extent, in the chronic phase. The same pattern for CB1 receptor density was observed in the cerebellum which, in this case, was accompanied by a progressive decrease in the capability of these receptors to activate GTP-binding proteins that was maximal in the chronic phase. The decrease in the density of CB1 receptors in the acute phase was also found in the globus pallidus but, in this case, the reduction was maintained during the further phases. No changes were observed in CB1 receptor-mRNA levels in any of the different regions examined. Finally, by contrast with the observations in motor structures, the status of CB1 receptors remained unaltered in cognition-related regions, such as the cerebral cortex and the hippocampus, during the different phases of CREAE. In summary, CB1 receptors were affected by the development of CREAE in mice exhibiting always down-regulatory responses that were circumscribed to motor-related regions and that were generally more marked during the acute and chronic phases. These observations may explain the efficacy of cannabinoid agonists to improve motor symptoms (spasticity, tremor, ataxia) typical of MS in both humans and animal models.

Animals↗

PubMed2006

Locally advanced and metastatic sarcoma (adult type) including gastrointestinal stromal tumors.

STS belong to the most challenging diseases in oncology that demand all resources of modern clinical oncology. With the improvement of surgical techniques and radiation therapy the majority of patients with localized disease can be cured. However, for patients with locally advanced or metastatic disease chemotherapeutic treatments have not greatly changed the poor outcome of the disease. The introduction of combined chemoradiotherapy as well as isolated limb-perfusion has improved the limb-salvage rate in locally advanced disease but the impact of systemic chemotherapy on overall survival remains a subject of dispute. For patients with metastatic sarcoma long-term survival can only be achieved in a small number of patients with mostly resectable disease. The list of effective drugs for palliative treatment in general still remains short and the duration of remissions usually does not exceed several months. The lack of alternative chemotherapeutic drugs imposes a considerable challenge in daily clinical practice with many young patients exhibiting a good performance status but progressive disease after standard treatment. A variety of new drugs or drug combinations seem to exhibit considerable activity in certain histological sarcoma subtypes, which may soon broaden the armamentarium of drugs for a subset of patients. However, with the vastly improved understanding of the biology and pathology of soft tissue sarcoma an era of opportunities seems to have begun and the recent success in the treatment of gastrointestinal stromal tumors impressively shows how fast a gain in the understanding of oncogenic mechanisms may translate into a highly efficient, clinically useful treatment.

Chemotherapy, Adjuvant↗

PubMed2005

Expression of somatostatin receptor subtypes (SSTR1-5) in Alzheimer's disease brain: an immunohistochemical analysis.

Somatostatin, widely distributed in human cortical brain regions, acts through specific high affinity somatostatin receptors (SSTR1-5) to exert profound effects on motor, sensory, behavioral, cognitive and autonomic functions. Somatostatin levels are consistently decreased in the cortex of Alzheimer's disease (AD) brain and in cerebrospinal fluid, and have become reproducible markers of this disease. In the present study, the distributional pattern of SSTR1-5 antigens in the frontal cortex of AD and age-matched control brains was studied using antipeptide polyclonal rabbit antibodies directed against the five human somatostatin receptor subtypes. All five SSTRs were differentially expressed as membrane and cytoplasmic proteins in cortical neurons with significant variations in control vs. AD brain. In AD cortical brain region, somatostatin and neuropeptide-Y-positive neurons decreased (>70%), and glial fibrillary acidic protein-positive astrocytes significantly increased (>130%) in comparison to control brain. SSTR2 and 4 were the predominant subtypes followed by SSTR1, 3 and 5. AD cortex showed a marked reduction in neuronal expression of SSTR4 and 5 and a modest decrease in SSTR2-like immunoreactivity without any changes in SSTR1 immunoreactive neurons. In contrast, SSTR3 was the only receptor subtype that increased in AD cortex. In AD cortex, SSTR1-, 3- and 4-like immunoreactivities were strongly expressed in glial cells but not SSTR2 and 5. These findings suggest the differential loss of immunoreactivity of SSTR2, 4 and 5 but not SSTR1, and increased SSTR3 in frontal cortex of AD brain as well as subtype-selective glial expression in AD brain. In summary, subtype-selective changes in the expression of SSTRs at protein levels in AD cortical regions suggest that somatostatin and SSTR-containing neurons are pathologically involved in AD and could possibly be used as markers of this disease.

Aged↗

PubMed2004

Expression of MUC1 (EMA) and E-cadherin in renal cell carcinoma: a systematic immunohistochemical analysis of 188 cases.

MUC1 (epithelial membrane antigen) is a membrane-associated mucin known to interfere with both cell-cell and cell-matrix adhesions. Overexpression has been associated with poor prognosis in a variety of cancers. We investigated the expression of MUC1 (using two different antibodies, MA695 and E29) and E-cadherin in renal cell carcinomas (137 conventional, 23 chromophobe, 20 papillary, and eight unclassified tumors) with respect to diagnostic and prognostic significance using a tissue microarray technique. Immunoreactivity was correlated with histological subtype, pT-stage, and grade using the chi2 test or the Fisher's exact test, respectively. Impact on disease-free survival was analyzed using the Kaplan-Meier method and the log-rank test. Immunoreactivity of more than 10% of cancer cells with MA695, E 29, and E-cadherin antibodies was found in 112/133 (84%), 86/133 (65%), and 7/131 (5%) conventional, 20/22 (91%), 19/22 (86%), and 21/22 (95%) chromophobe, 13/20 (65%), 8/20 (40%), and 3/20 (15%) papillary as well as 5/8 (63%), 5/8 (63%), and 4/8 (50%) unclassified carcinomas, respectively. The two different MUC1 antibodies yielded comparable staining results. A diffuse cytoplasmic staining pattern for MUC1 was found exclusively in chromophobe carcinomas, whereas conventional and papillary subtypes showed predominantly membranous staining (P<0.0001). Regarding papillary carcinomas, MUC1 was predominantly associated with type 1 (P=0.0001), and E-cadherin with type 2 (P=0.049) tumors. The cellular staining pattern of MUC1 in conventional tumors was related to pT-stage (P=0.002) and tumor grade (P=0.001): Low-stage (pT1/pT2) and grade (G1/G2) tumors showed a predominantly apical membranous staining, high-stage (pT3a/pT3b) and grade (G3/G4) tumors a predominantly circumferential membranous staining (with or without additional diffuse cytoplasmic immunoreactivity), which, in the conventional subtype, was associated with poor prognosis (P<0.0001). In conclusion, MUC1 and E-cadherin are diagnostically and prognostically useful markers in renal tumor pathology, especially when cellular staining patterns are considered.

Adult↗