PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “epithelial differentiation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2005

Epithelial differentiation in pancreatic development and neoplasia: new niches for nestin and Notch.

Changes in epithelial differentiation represent a characteristic early feature of human pancreatic cancer. Recent work suggests that many of these changes may reflect a pathologic recapitulation of developmental events. Reflecting this principle, metaplastic and neoplastic pancreatic epithelium appear to share many features in common with embryonic pancreatic epithelium, including reactivation of the Notch signaling pathway. In this review, we summarize recent studies involving regulation of epithelial differentiation in both embryonic and adult pancreas and highlight the role of Notch in regulating an exocrine progenitor pool.

Animals↗
PubMed2000

Strong association of SYT-SSX fusion type and morphologic epithelial differentiation in synovial sarcoma.

Synovial sarcoma is characterized by a specific recurrent translocation t(X; 18), resulting in either the SYT-SSX1 or SYT-SSX2 gene fusion. Because this is the primary genetic alteration in these tumors, we sought to identify the impact of molecular heterogeneity of the t(X;18) on cell proliferation, apoptosis, and epithelial differentiation in synovial sarcoma. Seventy-three patients with synovial sarcoma (18 biphasic, 55 monophasic) were selected on the basis of availability of tumor material for molecular and immunohistochemical analysis. Tumors were classified as biphasic on the basis of morphologic glandular differentiation. SYT-SSX fusion transcripts were examined by reverse transcriptase polymerase chain reaction using tumor RNA extracted from frozen or paraffin-embedded tissue. Cell proliferation was assessed immunohistochemically by the Ki-67 labeling index. Apoptosis was analyzed immunohistochemically with BAX and BCL2 antibodies and by the TUNEL method. Immunohistochemical evidence of epithelial differentiation was assessed using antibodies to cytokeratins and epithelial membrane antigen. Approximately two thirds of the tumors had an SYT-SSX1 and one third had an SYT-SSX2 fusion transcript. There was a strong association between SYT-SSX fusion type and histologic subtype. All biphasic synovial sarcomas had the SYT-SSX1 fusion, whereas all tumors with SYT-SSX2 were of monophasic morphology. There was, however, no association between SYT-SSX fusion type and expression of cytokeratins and epithelial membrane antigen among monophasic tumors. Tumors with SYT-SSX2 had a significantly higher mean and median Ki-67 labeling index than those with SYT-SSX1, but a comparison of Ki-67 according to fusion type, histologic type, and sample source suggested that the main determinants of proliferation rate were the latter two factors. Specifically, monophasic tumors and metastatic tumors showed significantly higher Ki-67 scores. Apoptosis (by TUNEL) was rarely observed, consistent with prominent expression of the anti-apoptotic protein BCL2 in almost all cases. TUNEL, BCL2, and BAX results did not correlate with SYT-SSX fusion type. These data confirm the strong association of SYT-SSX fusion transcript type with morphologic but not immunophenotypic epithelial differentiation in synovial sarcoma.

Apoptosis↗
PubMed1995

Epithelial differentiation antigens and epidermal growth factor receptors in transitional cell bladder carcinoma: correlation with prognosis.

Epithelial differentiation antigens have been correlated with morphologic differentiation of neoplastic urothelium. Moreover, epidermal growth factor, which is a polypeptide regulating growth and differentiation of normal and neoplastic cells, is found in high concentrations in the urine while its receptors (EGFR) have been identified in bladder tumors. The aim of this study was to investigate the immunohistochemical expression of cytokeratin, epithelial membrane antigen (EMA), CEA and EGFR in transitional cell bladder carcinomas (TCC) and to define any correlation of their expression with tumor grade, stage and patient survival. Twenty-four biopsy specimens obtained from patients with TCC were studied retrospectively. There were 23 men and 1 woman with a mean follow-up of 64 months. Eight biopsy specimens, which represented tumor recurrences of 4 patients, were also included in our material. The immunohistochemical avidin-biotin complex method was performed on paraffin sections for the detection of cytokeratin and EGFR with monoclonal antibodies as well as CEA with a polyclonal antibody. Cytokeratin was detected in 83.5% of the TCC, EMA in 62% and CEA in 70%. The expression of the epithelial differentiation antigens in TCCs was heterogenous, showing an increased incidence in high-grade and high-stage TCC. The CEA expression in TCC demonstrated a statistically significant correlation with patient survival (p < 0.02). EGFR was detected in 50% of the TCC. Although not statistically significant, a trend was found for a higher percentage of EGFR detection in high-grade TCC. EGFR expression was significantly associated with tumor stage and patient survival (p < 0.01 and p < 0.04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Epithelial differentiation and proliferative potential in spinal ependymomas.

The aim of this investigation was recognition of the epithelial differentiation and proliferative activity of ependymomas in the spinal cord compared with astrocytomas in the spinal cord and ependymoma in the brain. We investigated histopathological and immunohistochemical examination in thirty-five cases, including eleven ependymomas, thirteen astrocytomas in the spinal region and eleven ependymomas in the intracranial region. An anti-epithelial membrane antigen antibody (EMA), and two types of anti-cytokeratin antibodies, CAM 5.2 (45 and 52 kDa) and keratin (56 and 64 kDa) were applied as epithelial markers. The proliferative potential of the tumors was investigated using the Ki-67 labeling index (LI, %). Histologically, perivascular pseudorosettes were seen in all of the spinal and intracranial ependymomas. There were few ependymal structures in the spinal ependymomas except in the myxopapillary type. Immunohistochemical study demonstrated that nine (82%) were immunoreactive for EMA, eight (73%) were immunoreactive for CAM 5.2 and three (27%) were immunoreactive for keratin in the spinal ependymomas. In the spinal astrocytomas, no tumors were immunoreactive for EMA or CAM 5.2. One of thirteen cases was immunoreactive for keratin. The Ki-67 LI of the spinal ependymomas was lower than that of the intracranial ependymoma (p < 0.01). Epithelial differentiation was found in the ependymomas which may reflect the differences in histological and biological features between ependymomas and astrocytomas in the spinal cord. Regional differences in ependymomas may influence not only clinical features but also histo-pathological characteristics.

Adolescent↗
PubMed1984

Isolation and identification of enteroviruses from faecal samples in a differentiated epithelial cell line (HRT-18) derived from human rectal carcinoma.

A human rectal carcinoma-derived differentiated epithelial cell line, HRT-18, was inoculated with faecal samples in an attempt to grow coronavirus-like particles (CVLP), which are widely prevalent in human stools in southern India. While CVLP did not grow in this cell line, a variety of enteroviruses were isolated from 48 of the 114 stool samples from healthy controls and patients with diarrhoea. The results suggest that human gastrointestinal tumour-derived differentiated epithelial cells in continuous culture may be useful for the primary isolation of enteroviruses and merit further study.

Adult↗
PubMed1998

Induction of precocious pepsinogen synthesis by glucocorticoids in fetal rat gastric epithelium in organ culture: importance of mesenchyme for epithelial differentiation.

Glucocorticoids significantly affect both proliferation and differentiation of gastric epithelial cells in vivo. Here we examined the mechanism of action of glucocorticoids on the cells in vitro, with special reference to the epithelial-mesenchymal interaction. When 16.5-day fetal rat gastric explants were maintained in organ culture, the epithelial cells began to invaginate into mesenchyme on days 3 to 4, and formed glandular structures on days 5 to 6 in culture. Immunohistochemical analysis with specific antibodies revealed that pepsinogen-synthesizing cells first appeared on day 2, and they increased in number with epithelial morphogenesis to about 20%-30% of total epithelial cells on days 4 to 6, and that these cells were localized at the base of glandular structures in control media. When the explants were treated with hydrocortisone (1 microgram/ml), epithelial morphogenesis was mostly suppressed, but epithelial cytodifferentiation was significantly stimulated, indicating that epithelial morphogenesis is not necessary for their cytodifferentiation. In glucocorticoid-treated explants, pepsinogen-synthesizing cells first appeared on day 1, and more than 90% of the cells were positively stained with the antibodies from days 3 to 5 in culture. Biochemical analysis showed that much higher acid protease activity could be detected in glucocorticoid-treated explants than in controls from days 2 to 6 in culture, and analysis by zymography indicated that the synthesis of pepsinogen 1 but not cathepsin E was stimulated by the hormone. Northern blotting analysis showed that the level of pepsinogen 1 mRNA was greatly increased by glucocorticoids. Examination of the effect of the hormone on the epithelial proliferation showed that hydrocortisone (1 microgram/ml) significantly inhibited the epithelial growth from days 1 to 3 in culture. To investigate the role of epithelial-mesenchymal interaction in the glucocorticoid-induced differentiation of the gastric epithelial cells, effects of the hormone on the proliferation and differentiation of the cells in the absence of mesenchyme were examined, using a recently established primary culture system. The epithelial cells synthesized cathepsin E but not pepsinogen in cell culture, irrespective of glucocorticoid treatment, and the level of acid protease activity was not affected by the hormone, indicating that mesenchyme is necessary for the hormone to induce pepsinogen gene expression in the epithelial cells. In the cell culture system, glucocorticoids did not inhibit but significantly stimulated epithelial proliferation. This suggests that the hormone indirectly inhibited epithelial proliferation in organ culture, probably via mesenchyme. The mechanism of action of glucocorticoids on the epithelial-mesenchymal interaction in the fetal glandular stomach is discussed.

Animals↗
PubMed2003

Epithelial differentiation in medulloblastoma: comparison with other embryonal tumors of neuroectodermal origin.

Three cases of medulloblastoma characterized by epithelial differentiation are described in patients 6-months-, 1-month- and 8-years-old. Histologically, tumors from the two infant patients showed a perivascular arrangement without apparent radiated cytoplasmic processes from the vessels. Tumor cells displayed round and/or pleomorphic vesicular nuclei and a more abundant eosinophilic cytoplasm than that found in classic medulloblastoma. Neither Homer-Wright rosettes nor ependymal or ependymoblastic rosettes were noted in these tumors. The tumor in the 8-year-old patient exhibited a classic medulloblastoma component intermingled with abundant eosinophilic cytoplasm forming a tubular structure. Immunohistochemically, tumor cells in all cases were positive for cytokeratin, synaptophysin, and vimentin. In the third case involving the 8-year-old patient, epithelial tumor cells were positive for cytokeratin, whereas classic medulloblastoma components were negative for cytokeratin. Positive staining for melanoma-specific antigen was seen only in the third case, where strong reactivity of tumor cells formed a tubulus. However, the classic medulloblastoma component was negative for melanoma-specific antigen. Ultrastructurally, basal laminae were observed around tumor cells in the 6-month-old patient. These morphological and immunohistochemical features suggest that medulloblastoma with epithelial differentiation is a rare but distinct variant of medulloblastoma, and that some of these tumors should show differentiation in ocular pigment epithelium.

Antigens, Neoplasm↗
PubMed1996

Prostate epithelial differentiation is dictated by its surrounding stroma.

Prostate epithelial differentiation is dictated by its surrounding stroma which determines androgen induced growth responsiveness and expression of specific secretory proteins in normal prostate gland. During neoplastic progression, organ specific stroma has been shown to determine the rate of neoplastic progression from androgen-dependent to androgen-independent and metastatic states. Although growth factors and extracellular matrix are recognized as important contributors to prostate epithelial growth, hormonal responsiveness, and neoplastic progression, the exact mechanism of intercellular communication between stromal and epithelial cells remains undefined. In addition to the importance of defining the reciprocal interaction between stromal and epithelial interaction in the prostate, clonal interaction between two dissimilar prostate epithelial cell is also recognized to contribute to disease progression. In this review, we summarized recent advances made in delineating molecular mechanisms underlying stromal epithelial interaction and clonal interaction between androgen-dependent and androgen-independent prostate cancer cells in vivo and in culture. Understanding cellular interaction between prostate epithelium and its surrounding stroma could help us in developing metastatic models of prostate carcinogenesis. This concept will allow us to define epithelial-specific markers, markers induced as the result of stromal-epithelial interaction, and stroma-associated markers. These markers together will assist us in diagnosing, preventing, prognosing and treating prostate cancer more efficaciously in the future.

Androgens↗
PubMedDate not supplied

Ewing's sarcoma with epithelial differentiation: fine structural and immunocytochemical study.

A femoral Ewing's sarcoma from a 13 1/2-year-old girl with otherwise typical clinical and pathological features showed epithelial differentiation by electron microscopy and immunocytochemistry. The expression of keratin and the presence of tonofilaments in cells of this Ewing's sarcoma may enforce the hypothesis that Ewing's sarcoma derives from a multipotential primitive stem cell.

Adolescent↗
PubMed2003

Pulmonary well-differentiated fetal adenocarcinoma expressing lineage-specific transcription factors (TTF-1 and GATA-6) to respiratory epithelial differentiation: an immunohistochemical and ultrastructural study.

A case of pulmonary well-differentiated fetal adenocarcinoma was examined with conventional histological, immunohistochemical, and ultrastructural studies that revealed the distribution of lineage-specific transcription factors (TTF-1 and GATA-6). The patient was a 33-year-old Japanese woman, who underwent resection of the right lower lobe for the lung tumor. The tumor demonstrated an organized histology mimicking the epithelial differentiation of fetal lung with peculiar glands and moruloid cell nests, without mesenchymal proliferation. Adenocarcinoma cells forming the atypical glands were similar to the epithelial cells of the branching tubules in the pseudo glandular stage of the fetal lung. Distribution of TTF-1 was observed in many of the nuclei of the adenocarcinoma cells forming the glands. Tumor cells in the morula were primitive epithelial cells with some immunohistochemical neuroendocrine cell differentiation and some of them showed GATA-6-positive stains in the nuclei. In the ultrastructural study, adenocarcinoma cells showed little differentiation toward mucous cells and ciliated cells. Neuroendocrine granules were seen in a few tumor cells in the morula. In the present case, tumor cells forming the peculiar histological, molecular, and ultrastructural constructions showed partial and incomplete mimicry of the morphogenesis of respiratory epithelium.

Adenocarcinoma↗
PubMed2000

Extracellular adenosine deprivation induces epithelial differentiation of HT29 cells: evidence for a concomitant adenosine A(1)/A(2) receptor balance regulation.

HT29 cells display an undifferentiated phenotype in culture. However, numerous treatments are able to induce both epithelial differentiation and cell growth inhibition. We have previously demonstrated that adenosine and its analogues act through specific adenosine receptors to modulate cell proliferation in HT29 and other human colon adenocarcinoma cell lines. Among the treatments tested, the most potent inhibition of HT29 cell growth was induced by deprivation of extracellular adenosine using adenosine deaminase. Here, we investigated the capacity of adenosine deaminase to initiate epithelial differentiation. After 1 month of daily addition of 10 U/ml adenosine deaminase to the culture medium, HT29 cells were cloned by limited dilution. Among the clones obtained, we focused our attention on clone 13. Microscopic visualization and proliferation studies indicated that cells from this clone grew very slowly and in a pseudo-monolayer, in marked contrast with the situation observed in the mother HT29 cell line. In addition, clone 13 cells displayed epithelial features that mimic the enterocytic differentiation of Caco-2 cells. These modifications were accompanied by dramatic changes in the activity of adenosine receptors, as demonstrated by pharmacological studies. In contrast to the original HT29 cells, clone 13 as well as Caco-2 cells displayed (i) a very low number of adenosine A(1) receptors, and (ii) increases in intracellular cAMP levels when challenged with adenosine analogues. It is hypothesized that a loss of adenosine A(1) receptors, with no change or a concomitant increase in adenosine A(2) receptors, results in the emergence of adenosine A(2) receptor-mediated differentiation and inhibition of proliferation, through a cAMP-dependent pathway.

Adenosine↗
PubMed1994

Stromal expression of tenascin is inversely correlated to epithelial differentiation of hormone dependent tissues.

We were previously investigating the expression of the extracellular matrix glycoprotein tenascin in normal and malignant endometrial tissues of humans and rodents. These studies suggested that the expression of tenascin was induced by proliferating epithelia (normal and particularly malignant) and was downregulated with their differentiation. The aim of this study was to investigate the hormone dependency of tenascin expression in (a) the transplantable EnDA endometrial tumor model with or without estrogen deprivation (ovariectomy) of the animals, (b) DMBA-induced rat mammary tumors with or without a hormonal treatment of the animals [ovariectomy, antiestrogen (tamoxifen) or antiprogestin (ZK 98299) treatment] and (c) in the rat prostate of untreated or androgen deprived animals (orchiectomy, flutamide-, casodex- or cyproterone acetate (CPA)-treatment). 1. Estrogen withdrawal by ovariectomy did not affect tenascin expression in transplantable EnDA endometrial adenocarcinoma, meaning the entire extracellular space of the stromal mesenchyme was decorated by tenascin immunoreactivity. 2. In untreated DMBA-induced rat mammary tumors almost the entire extracellular space of the stroma was stained by tenascin immunoreactivity. Ovariectomy and antiestrogen treatment did not affect tenascin expression. In contrast, antiprogestin treatment induced terminal differentiation of mammary tumor cells and in parallel downregulated tenascin expression. 3. In the normal rat prostate no tenascin was detectable by immunocytochemistry. However, following androgen deprivation we found tenascin expression in the stroma of the prostate. The most prominent expression was observable after CPA-treatment, possibly due to its progestagenic potency. In conclusion, the hormones and antihormones tested show no direct effect on the stromal expression of tenascin. However, proliferative activity and a low degree of differentiation of the epithelium induces tenascin expression, whereas epithelial differentiation apparently shuts down tenascin expression. Preliminary in vitro studies suggest that paracrine acting growth factors trigger the hormonal regulation of tenascin expression.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

The Caenorhabditis elegans gene lin-26 can trigger epithelial differentiation without conferring tissue specificity.

How epithelial cell fates become specified is poorly understood. We have previously shown that the putative C2H2 zinc-finger transcription factor LIN-26 is required for the differentiation of ectodermal and mesodermal epithelial cells in Caenorhabditis elegans. Here, we report that ectopic LIN-26 expression during early gastrulation transforms most blastomeres into epithelial-like cells. Specifically, LIN-26 induced the expression of three epithelial markers: the adherens junction protein JAM-1; DLG-1, which is essential for the assembly of JAM-1 at junctions; and CHE-14, which is involved in apical trafficking. Furthermore, ultrastructural studies revealed that ectopic LIN-26 expression induced the formation of adherens-like junctions. However, ectopic lin-26 expression did not confer any tissue-specific cell fate, such as the epidermal cell fate, as evidenced from the observation that several epidermal-specific genes were not induced. Conversely, we show that epidermal cells displayed some polarity defects in lin-26 mutants. We conclude that lin-26 can induce epithelial differentiation and that epitheliogenesis is not a default pathway in C. elegans.

Animals↗
PubMed1993

Predominant expression of nPKC eta, a Ca(2+)-independent isoform of protein kinase C in epithelial tissues, in association with epithelial differentiation.

Of the nine known members of the protein kinase C (PKC) family, we found that novel (n-) PKC eta, a newly isolated Ca(2+)-independent isoform, was expressed at the highest level in the epidermis of mouse skin and epithelia of the digestive and respiratory tracts including the tongue, esophagus, forestomach, glandular stomach, intestine, colon, trachea, and bronchus. Expression of nPKC eta mRNA in these epithelial tissues was 3-10 times that in the brain and was especially high in squamous epithelium. Two other PKC isoforms, conventional (c-) PKC alpha and nPKC delta, were also expressed in these epithelial tissues, but no cPKC gamma was detected. In situ hybridization and immunohistochemical analyses demonstrated the localization of nPKC eta in suprabasal layers of the skin, tongue, esophagus, and forestomach. In the intestine, it was expressed in the epithelial cells of villi, but not of crypts. In the lung, only bronchial epithelium expressed nPKC eta. The localization of nPKC eta in differentiating or differentiated epithelial cells, rather than in proliferating basal cells, suggests the involvement of nPKC eta in epithelial differentiation.

Amino Acid Sequence↗
PubMedDate not supplied

Phenotypic and genotypic characterization of glioblastoma multiforme with epithelial differentiation and adenoid formations.

Rare examples of high-grade gliomas show focal epithelial differentiation, which may require distinction from colliision tumors. These epithelial constituents are not well-characterized immunophenotypically and have rarely been subjected to genotyping. We describe a case of a 54-year-old female with a short history of hemiparesis who was found to have an absolute lymphocytosis and a heterogeneously enhancing frontotemporal tumor. Cytological and histological examination of brain biopsies confirmed the presence of a glioblastoma multiforme also containing CAM5.2/CK7/BerEP4/CEA/EMA-immunopositive and GFAP-immunonegative nests of epithelial cells with a high proliferative index and focal glandular differentiation. Hematological investigations confirmed a diagn of chronic lymphocytic leukemia (CLL) with no demonstrable CNS involvement. Genetic analysis using microsatellite markers and specimens obtained by laser capture microdissection of the CNS tumor and normal brain tissue, showed that both the glial and epithelial components of the brain tumor had identical losses of 2/2 informative markers on chromosome 17p13 and 5/5 informative markers on chromosome 10q22-26. The glial and epithelial components also shared an identical 2 base pair deletion in the TP53 gene at codon 209, exon 6, introducing a stop codon at codon 214. No losses at any of the above loci and no TP53 mutation were detected in the leukemic cells. These results suggest both components of the brain tumor, although differing in phenotype, share the same genetic lineage.

Brain Neoplasms↗
PubMed1985

Distribution of vimentin, cytokeratins, and desmosomal-plaque proteins in human nephroblastoma as revealed by specific antibodies: co-existence of cell groups of different degrees of epithelial differentiation.

The distribution of cytokeratins, desmosomal-plaque proteins (desmoplakins), and vimentin in nephroblastoma tissue was studied by immunofluorescence microscopy using specific antibodies. In undifferentiated blastema cells, desmosomes, as revealed by antibodies to desmoplakins, preceded the advent of significant amounts of cytokeratins, indicating that desmosomes are early and sensitive markers of epithelial differentiation. Cytokeratin-positive tumor cells were seen in the following distribution patterns: groups of loosely arranged and scattered cells containing only scant cytokeratin fibrils surrounded by negative stroma cells; focal accumulation of cytokeratin-positive cells with cytokeratin-specific cytoplasmic fibril meshwork staining; rosettes of cytokeratin-positive cells without formation of distinct lumina, showing concentration of cytokeratin staining in the center; tubules with distinct lumina made up of cytokeratin-positive cells, with cytokeratin staining concentrated in the subapical cell portions. In cytokeratin-positive cells, the numbers of desmoplakin-positive dots were generally increased; in well-formed tubules, enrichment of desmoplakin-positive spots, corresponding to the subapical skeletal disks, was most conspicuous. Vimentin was demonstrated in stromal areas, but also in blastema cells showing coexpression of desmosomes and vimentin filaments. Moreover, in certain blastema cells, an overlap of cytokeratin and vimentin immunostaining was observed. Epithelial cells of nephroblastoma tubules did not react with vimentin antibodies. Our results show that the appearance of desmosomal plaques, as demonstrated by antibodies to desmoplakins, may be a very early feature of epithelial differentiation, and they also emphasize the value of antibodies to desmoplakins in tumor cell typing and diagnosis.

Cell Differentiation↗
PubMedDate not supplied

Osteogenic sarcoma with epithelial differentiation.

This case report details an osteogenic sarcoma arising in a vertebra in which cytokeratin intermediate filaments were detected immunohistochemically with three different antibodies. This feature was present not only in the primary neoplasm but also in two local recurrences and a metastasis to the iliac bone. What is unique about this primary bone tumor, however, is the structural evidence for epithelial differentiation. Ultrastructurally, well-formed desmosomes and tonofilaments were present in all four surgically resected specimens. This tumor expands the list of soft tissue and bone tumors in which anomalous expression of intermediate filaments can occur but, more important, illustrates that changes in genetic expression of neoplasia of mesenchymal origin can result in paradoxic epithelial differentiation.

Adult↗