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PubMed1989

A study of 39 retinoblastomas with particular reference to morphology, cellular differentiation and tumour origin.

A series of 39 retinoblastomas was studied using light microscopy and immunohistochemistry for localization of neurone-specific enolase and glial fibrillary acidic protein. Thirty-eight retinoblastomas (97.4%) occurred in children less than 6 years of age: one was in a 61-year-old man (2.6%); the mean age, excluding the 61-year-old, was 32.1 months. Unilateral tumours were found in 74.4% of patients and bilateral tumours in 25.6%; bilateral lesions occurred in a younger age group, mean age of 21.7 vs 35.9 months. The male to female ratio was 1.4:1. Morphologically, arrangement of tumour cells into trabeculae was noted in 69.2% of retinoblastomas and glomerulus-like structures in 43.6%. These two patterns of cellular arrangement were encountered where the choroid and sclera were invaded by neoplastic cells. Homer Wright rosettes were observed in all tumours. Flexner-Winstersteiner rosettes in 33.3% and fleurettes in 2.6%. Differentiation into neoplastic neurones as well as in the form of Flexner-Winstersteiner rosettes and fleurettes was noted in 46.1%, neoplastic ependymal cells in 100.0%, astrocytes in 58.9%, oligodendrocytes in 23.1%, and glioblastomas in 2.6%. These data suggest that retinoblastoma is a primitive stem cell neuroectodermal tumour with the capacity for differentiation in both neuronal and neuroglial directions.

Aged↗
PubMed2003

Host oyster tissue extracts modulate in vitro protease expression and cellular differentiation in the protozoan parasite, Perkinsus marinus.

Perkinsus marinus is responsible for a chronic disease (Dermo) of the Eastern oyster, Crassostrea virginica. In order to simulate the in vivo environment more closely, a chemically defined medium (JL-ODRP-3) was supplemented with tissue homogenate extracts or plasma from oysters possessing varying degrees of susceptibility to P. marinus infection. In media supplemented with extracts from highly susceptible oysters (C. virginica), P. marinus cells secreted elevated amounts of a set of low molecular weight serine proteases (LMP: 30-45 kDa) as assessed by enhanced digestion within gelatin-substrate SDS-PAGE gels. Oyster species of low susceptibility (C. gigas and C. ariakensis) did not exhibit this ability to upregulate P. marinus LMP expression. Oyster extract supplementation also led to pronounced changes in P. marinus cellular morphology, such that the cells were comparable to those observed within naturally infected oysters.

Animals↗
PubMed1982

Immunosuppressive properties of polar organic compounds that induce cellular differentiation in Friend erythroleukemia cells.

We studied the effect of several polar organic compounds, known to induce erythroid differentiation in Friend leukemia (FL) cells, on in vitro human lymphocyte responses and on skin graft survival in mice. The short chain fatty acids, butyric acid (BA), propionic acid (PA), valeric acid, and the polar organic solvents, dimethyl sulfoxide, dimethylformamide, and dimethylacetamide, all mediated significant inhibition of alloantigen-induced proliferation and generation of cytotoxic T lymphocytes (CTLs) in human primary and secondary mixed lymphocyte culture (MLC) reactions. Hexamethylenebisacetemide, another potent inducer of differentiation in FL cells, also mediated significant suppression. Inhibition of MLC with polar organic compounds was accomplished at concentrations known to induce differentiation in FL cells and that are not cytotoxic to peripheral blood mononuclear cells. In distinct contrast, agents that are structurally related to BA, but that do not induce differentiation in FL cells, such as caproic acid, beta-OHBA, gamma-amino BA, and isobutyric acid, did not exhibit immunosuppressive properties. Pokeweed mitogen-driven polyclonal B cell activation was also suppressed by agents that induce erythroid differentiation in FL cells. In addition to potent in vitro immunosuppressive properties, supplementation of drinking water with BA or PA resulted in prolongation of full-thickness skin grafts in DBA/2 (H-2d) to C57BL/6 (H-2b) donor-recipient combinations. Our findings indicate that polar organic compounds that induce differentiation in FL cells are potent immunosuppressive agents.

3-Hydroxybutyric Acid↗
PubMed2004

New roles for CDC25 in growth control, galactose regulation and cellular differentiation in Saccharomyces cerevisiae.

Living organisms display large differences in stress resistance throughout their life cycles. To study the coordinated regulation of development and stress responses in exponentially growing yeast, mutants that displayed elevated heat-shock resistance at this stage were screened for. Here, two new mutant alleles of CDC25 in Saccharomyces cerevisiae, cdc25-21 and cdc25-22, are described. During exponential growth in glucose at 25 degrees C, these mutants are resistant to heat, oxidative, osmotic and ionic shock, accumulate stress-protein transcripts, show slow growth rates, thick cell walls and glycogen hyperaccumulation and lack cAMP signalling in response to glucose. Genetic and cellular analyses revealed that the stationary-phase phenotypes of cdc25-21 and cdc25-22 mutants are not due to entrance to a G(0) state during exponential growth, but are the result of a prolonged G(1) phase. It was found that, in the W303 background, CDC25 is dispensable for growth in glucose media. However, CDC25 is essential for growth in galactose, in non-fermentable carbon sources and under continuous incubation at 38 degrees C. In conclusion, the function of the catalytic, C-terminal domain of Cdc25p is not only important for fermentative growth, but also for growth in non-fermentable carbon sources and to trigger galactose derepression.

Adaptation, Physiological↗
PubMedDate not supplied

Promoter specific sensitivity to inhibition of histone deacetylases: implications for hormonal gene control, cellular differentiation and cancer.

Alterations in histone acetylation status appear to play a central role in the regulation of neoplasia, tumor suppression, cell cycle control, hormone responsiveness and senescence. These alterations of chromatin control gene transcription. The histone acetylation status is regulated by the equilibrium of histone acetyl-transferase activity (HAT) and the histone deacetylase activity (HDAC). Commonly, DNA-transfection assays are used to measure the effect of histone acetylation and deacetylation on gene transcription. Here we have analyzed the response of various viral long terminal repeats and vertebrate promoters to the specific histone deacetylase inhibitor trichostatin A (TSA). We show that the activity of many, but not all, promoters is increased upon TSA treatment. Interestingly, the lysozyme promoter exhibited TSA resistance, while the activity of metallothionine, the human growth hormone, and the thymidine kinase promoters was increased. Furthermore, we found that all tested viral promoters are induced by TSA. Analysis of the transcriptional behaviour of the thyroid hormone receptor (TR), the cellular homologue of the v-erbA oncogene, revealed that TSA reduced the gene silencing function but had no influence on the hormone-induced gene activation function of the receptor. These results on gene specific effects, together with the HDAC structural data (1), may be a basis for the development of HDAC inhibitors as antitumor agents.

Animals↗
PubMed1997

Adeno-associated virus type 2-mediated transduction in primary human bone marrow-derived CD34+ hematopoietic progenitor cells: donor variation and correlation of transgene expression with cellular differentiation.

Although the adeno-associated virus type 2 (AAV) is known to possess a broad host range that transcends the species barrier, we suggested in an earlier study that AAV infection of human cells is receptor mediated (S. Ponnazhagan et al., J. Gen. Virol. 77:1111-1122, 1996). In the present studies, we investigated the ability of AAV to infect primary human hematopoietic progenitor cells capable of multilineage differentiation. Bone marrow-derived CD34+ cells from 12 hematologically normal volunteer donors were infected with a recombinant AAV containing the beta-galactosidase gene under the control of the cytomegalovirus immediate-early promoter (vCMVp-lacZ). Whereas 15 to 80% of the cells from approximately 50% of the donors showed various levels of lacZ gene expression, the expression was undetectable in cells from the remaining donors. However, if cells from both sets of donors were stimulated with various combinations of cytokines to induce differentiation into myeloid and lymphoid lineages following AAV infection, then the level of expression of the transduced gene increased up to 20-fold over a period of 14 days. The results of virus-binding assays suggested that the observed difference between the two groups was due to the differential susceptibility of CD34+ cells to AAV infection rather than to differences in transcription and translation of the transduced gene. To corroborate these results, CD34+ cells from the two donor groups, KB (human nasopharyngeal carcinoma) cells, and M07e (human megakaryocytic leukemia) cells were infected with vCMVp-lacZ. KB cells served as a positive control for AAV infection, and M07e cells served as a negative control. Whereas abundant hybridization to the single-stranded viral DNA on Southern blots was detected in KB and CD34+ cells that were positive for lacZ gene expression, little activity was detected in M07e and CD34+ cells that did not show expression of the lacZ gene. These results suggest that the levels of expression of the putative cellular receptor for AAV vary widely in CD34+ cells from different donors. These studies have implications for the potential use of AAV vectors in human gene therapy involving primary human primitive hematopoietic stem and progenitor cells.

Antigens, CD34↗
PubMed1986

Expression of cytokeratins in normal and neoplastic colonic epithelial cells. Implications for cellular differentiation and carcinogenesis.

Cells of the normal colonic mucosa express several types of cytokeratins, the characteristic intermediate filament proteins of epithelial cells. An immunohistochemical study was designed to examine the expression of two distinct groups of cytokeratins, recognized by monoclonal antibodies AE1 and AE3, in the colonic mucosa and to compare the findings with those obtained with a large number of polypoid lesions (adenomatous and hyperplastic) and carcinomas of the colon. AE1 and AE3 immunostaining was found in the surface epithelium and upper portions of the crypts of Lieberkühn (functional zone) of normal colonic mucosa, whereas the lower portions of the crypts (proliferative compartment) were unreactive with both AE1 and AE3. Polypoid lesions of the colonic mucosa can be placed into two categories based on their patterns of cytokeratin expression. Solitary tubular adenomas and hyperplastic polyps are composed of AE1 and AE3 nonexpressing cells with only few, patchy areas of AE1 and AE3 expressing cells present within glands and in the surface epithelium. In contrast, villous adenomas show strong AE1 and AE3 reactivity throughout the glands. Furthermore, tubular and villous adenomas, and even histologically normal mucosa in patients with familial polyposis, show AE1/AE3 expression throughout the glands and surface epithelium. Colonic carcinomas show a predominance of AE1/AE3 expressing cells. Thus, cytokeratins recognized by monoclonal antibodies AE1 and AE3 represent molecular markers of cellular maturation in the normal colonic mucosa, that are expressed in colonic carcinomas and, in addition, serve as markers that distinguish colonic mucosa and adenomas with a high risk for development of cancers from those with a lower risk.

Adenocarcinoma↗
PubMed2000

Differential cellular regulation of the mitochondrial permeability transition in an in vitro model of 1,3-dinitrobenzene-induced encephalopathy.

Exposure to 1,3-dinitrobenzene (DNB) is associated with neuropathologic changes in specific brainstem nuclei, mediated by oxidative stress and mitochondrial dysfunction. The expression of Bcl-2-family proteins as a function of sensitivity to 1, 3-dinitrobenzene (DNB)-induced mitochondrial permeability transition (MPT) was examined in C6 glioma and SY5Y neuroblastoma cells. Neuroblastoma cells were 10-fold more sensitive than glioma cells to DNB-induced decreases in mitochondrial reducing potential, measured by reduction of the tetrazolium compound, 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). The IC(50) values for DNB-related inhibition of MTT reduction were 107+/-25 microM in SY5Y cells and 1047+/-101 microM in C6 cells. Levels of reactive oxygen species (ROS) were increased in both SY5Y and C6 cells following DNB exposure by 4.6- and 6.0-fold above control, respectively. DNB caused abrupt depolarization of mitochondria in both neuroblastoma and glioma cells that was inhibited by trifluoperazine. The first order rate constants for mitochondrial depolarization were: C6, k=0.31+/-0.02 min(-1); SY5Y, k=0.14+/-0.01 min(-1). Onset of MPT occurred at 10-fold lower concentration of DNB in SY5Y cells than in C6 cells. The antioxidants, deferoxamine and alpha-tocopherol, effectively prevented DNB-induced MPT in C6 and SY5Y cells, suggesting involvement of ROS in the initiation of MPT. Exposure to DNB resulted in decreased cellular ATP content in SY5Y cells and efflux of mitochondrial calcium in both SY5Y and C6 cells, concurrent with onset of MPT. The expression of Bcl-2, Bcl-X(L), and Bax was evaluated in both cell types by Western blot analysis. C6 glioma cells strongly expressed Bcl-X(L) and only weakly expressed Bcl-2 and Bax, whereas SY5Y neuroblastoma cells expressed lower levels of Bcl-X(L) and higher levels of both Bcl-2 and Bax. Collectively, these results suggest that higher constitutive expression of Bcl-X(L), rather than Bcl-2, correlates with resistance to DNB-induced MPT in SY5Y and C6 cells and that differential regulation of the permeability transition pore may underlie the cell-specific neurotoxicity of DNB.

Adenosine Triphosphate↗
PubMed2001

K(V)alpha1 channels in murine arterioles: differential cellular expression and regulation of diameter.

The primary objectives of this study were to reveal cell-specific expression patterns and functions of voltage-gated K(+) channel (K(V)alpha1) subunits in precapillary arterioles of the murine cerebral circulation. K(V)alpha1 were detected using peptide-specific antibodies in immunofluorescence and Western blotting assays. K(V)1.2 was localized almost exclusively to endothelial cells, whereas K(V)1.5 was discretely localized to the nerves and nerve terminals that innervate the arterioles. K(V)1.5 also localized specifically to arteriolar nerves in human pial membrane. K(V)1.5 was notable for its absence from smooth muscle cells. K(V)1.3, K(V)1.4, and K(V)1.6 were localized to endothelial and smooth muscle cells, although K(V)1.4 had a low expression level. K(V)1.1 was not expressed. Therefore, we show that different cell types of pial arterioles have distinct physiological expression profiles of K(V)alpha1, conferring the possibility of differential modulation by extracellular and second messengers. Furthermore, we show recombinant agitoxin-2 and margatoxin are potent vasoconstrictors, suggesting that K(V)alpha1 subunits have a major function in determining arteriolar resistance to blood flow.

Animals↗
PubMed2003

Differential cellular distribution of HIV-1 drug resistance in vivo: evidence for infection of CD8+ T cells during HAART.

This study presents a detailed analysis of HIV-1 populations isolated from total PBMC, plasma, CD4+ T cells, CD8+ T cells, and monocytes/macrophages in 13 patients receiving HAART. Sequence analysis of the reverse transcriptase and protease genes indicated that viral strains isolated from different blood leukocytes were genetically distinct in each subject. Notably, HIV variants isolated from CD8+ T cells were distantly related to strains derived from other blood cell types, providing evidence for the strain-specific infection of CD8+ T cells in vivo. Compartmentalization of drug resistance mutations in specific blood cell types was observed in approximately 50% of patients. The prevalence of resistance mutations was higher in either CD4+ T cells or monocytes/macrophages in these subjects. However, CD8+ T cells showed markedly lower levels of viral drug resistance in these patients, indicating a lack of viral replication in this compartment. This study is the first to demonstrate the differential distribution of HIV drug resistance in different blood cell types during HAART and provides new insights into the infection of CD8+ T cells in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Per and neuropeptide expression in the rat suprachiasmatic nuclei: compartmentalization and differential cellular induction by light.

Per1 and Per2, two clock genes rhythmically expressed in the suprachiasmatic nucleus (SCN), are implicated in the molecular mechanism of the circadian pacemaker and play a major role in its entrainment by light. To date, it is not known if every cell of the SCN, a heterogeneous structure in respect of neuropeptide content, expresses clock genes equally. The aim of this study was to identify, by single and double non-radioactive and/or radioactive hybridizations, the cell types (AVP, VIP and GRP) expressing Per1 or Per2 in the SCN of rats, (1) when Per are highly expressed during the daytime, and (2) after induction of Per expression by a light pulse at night. Our results indicate that, during the daytime, Per1 and Per2 genes are both mainly expressed in the AVP cells of the dorso-median part of the SCN, whereas only a few VIP cells in the ventral part of the SCN exhibit Per gene expression. In contrast, following a light pulse at night, there is differential induction of the two Per genes. Per1 expression essentially occurs in the ventro-lateral GRP cells, while Per2 expression is not restricted to the retinorecipient part of the SCN as it also occurs in AVP cells. Altogether, our results suggest that Per1 and Per2 are mainly expressed in AVP cells during the daytime and suggest that GRP cells play an important role in resetting of the clock by light.

Animals↗
PubMed1990

Differential cellular catabolism of 111In, 90Y and 125I radiolabeled T101 anti-CD5 monoclonal antibody.

We evaluated the differences in catabolism of 125I, 111In and 90Y-T101 monoclonal antibody (anti-CD5) by peripheral blood mononuclear cells (PBMNC), HUT 102, CCRF-CEM and MOLT-4 cells. All cells showed higher retention of 111In than of 125I. PBMNC showed similar retention of 90Y and 111In. The release of 125I was reduced by using metabolic inhibitors, F(ab')2 of T101, pure lymphocytes or incubating at 4 degrees C. Our findings suggest differences in the intracellular catabolism of the radionuclides.

Animals↗
PubMed2001

Differential cellular targets of Epstein-Barr virus (EBV) infection between acute EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection.

Unusual Epstein-Barr virus (EBV) infection into T or natural killer cells plays a pivotal role in the pathogenesis of acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV). The precise frequency and localization of EBV genome in lymphocyte subpopulations especially within T-cell subpopulations are unclear in these EBV-related disorders. This study analyzed the frequency of EBV-infected cells in circulating lymphocyte subpopulations from 4 patients with acute EBV-HLH and 4 with CAEBV. EBV- encoded small RNA-1 in situ hybridization examination of peripheral blood lymphocytes showed a significantly higher frequency of EBV-infected cells of 1.0% to 13.4% in EBV-HLH and 1.6% to 25.6% in CAEBV, respectively. The patterns of EBV infection in lymphocyte subpopulations were quite different between acute EBV-HLH and CAEBV. EBV infection was predominant in CD8(+) T cells in all EBV-HLH patients, whereas the dominant EBV-infected cell populations were non-CD8(+) lymphocyte subpopulations in CAEBV patients. Phenotypical analysis revealed that EBV-infected cell populations from both EBV-HLH and CAEBV were activated. There was no predominance of any EBV substrain of latent membrane protein-1, EBV-associated nuclear antigen (EBNA)-1, and EBNA-2 genes between the 2 abnormal EBV-associated disorders, and self-limited acute infectious mononucleosis. These results showing differential virus-cell interactions between acute EBV-HLH and CAEBV indicated different pathogenic mechanisms against EBV infection between the 2 EBV-associated diseases, which accounts for the difference in clinical manifestations between the 2 diseases.

Acute Disease↗
PubMed2001

Differential cellular compartmentalization of the nuclear receptor SpSHR2 splicing variants in early sea urchin embryos.

SpSHR2 is a member of the nuclear receptor superfamily, expressed in embryos, larvae, and adult tissues of sea urchin. During embryonic development, two receptor isoforms are produced via alternative splicing. One exhibits the typical structure of nuclear receptors (SpSHR2-full length), whereas the other is missing the entire LBD (SpSHR2-splice variant). DNA-constructs encoding these isoforms and two additional in vitro generated deletion mutants were engineered in an expression vector carrying the myc-tag. Expression of the tagged isoforms in S. purpuratus embryos showed that the exogenous SpSHR2 full-length protein displays a similar subcellular localization as the endogenous receptor. In early cleavage stages (4-cells), the full-length isoform is predominantly localized in the nucleus, whereas two cell divisions later (16-cells) protein accumulations are detected in both the nucleus and cytoplasm. To the contrary, the SpSHR2-splice variant is confined in the embryonic nuclei both at 4- and 16-cell stage embryos. Analysis of the intracellular distribution of two receptor mutants, one having a deletion within the DBD (DeltaP) and the other a truncation of the C-terminal F-domain (DeltaF), revealed that DeltaP is localized similarly to full-length receptor, whereas DeltaF is maintained in the nucleus, similar to the SpSHR2 splice variant. Investigation of the DNA binding and dimerization properties of the two SpSHR2 isoforms demonstrated that they recognize and bind to a DR1-element as monomers, whereas DeltaP does not bind DNA and DeltaF binds to DR1 poorly. These results suggest that the receptor's putative LBD is responsible for the differential subcellular localization of the two natural SpSHR2-isoforms in early development.

Active Transport, Cell Nucleus↗
PubMed1991

Triple immunofluorescence confocal laser scanning microscopy: spatial correlation of novel cellular differentiation markers in human muscle biopsies.

Two different methods for triple immunofluorescence imaging with a confocal laser scanning microscope (CLSM) are described. The methods enable spatial "mapping" of 3 different epitope distribution patterns simultaneously in one tissue section. The key to triple imaging includes: (a) specific immunolabeling with 3 different mouse monoclonal antibodies (mAbs), (b) localization of the antibody binding sites by 3 different dyes, (c) spectral isolation of each dye by using selective band pass or long pass emission filters, (d) computerized imaging of the fluorescences as colored overlays or as selective signals in each optical section through the tissue in the z-direction. Method 1 consists of the combination of fluorescein isothiocyanate (FITC), phycoerythrin R (PE), and Texas Red (TR) as fluorescent markers. These dyes can be imaged by using 488 nm and 543 nm excitation laser lines. In method 2 aminomethyl coumarin acetic acid (AMCA) was combined with FITC and PE. For this application the CLSM was adapted to ultraviolet microscopy that enabled the use of 3 laser lines (364 nm, 488 nm, 543 nm) for excitations. Cryostat sections of diagnostic human muscle biopsies (n = 9) were studied which were normal by ordinary light microscopic examination. Sections were incubated with mAbs specific for: (1) the fast myosin heavy chain (My32); (2) the major histocompatibility class II antigen HLA-DR; (3) the lymph node homing receptor Leu8, and (4) the cell adhesion receptor OKM5 (CD36). By combining these mAbs in triple staining procedures, 3 capillary types and 4 different phenotypes expressed by muscle fibers were identified simultaneously. The mAbs Leu8 and OKM5, widely used as leukocyte typing antibodies in the blood, exhibit hitherto unrecognized specificities for antigens displayed by muscle fibers. At the level of these markers, specific spatial correlations between OKM5 reactive capillaries and both OKM5 reactive and nonreactive muscle fiber types become visible. The presented results provide direct evidence for cellular complexity and novel insight into the immunoanatomical architecture of skeletal muscle. The methods may be of general significance for the construction and quantification of three-dimensional multiparameter "maps" of cells and tissues.

Adult↗
PubMed1999

Role of lon and ClpX in the post-translational regulation of a sigma subunit of RNA polymerase required for cellular differentiation in Bacillus subtilis.

The RNA polymerase sigma subunit, sigmaH (Spo0H) of Bacillus subtilis, is essential for the transcription of genes that function in sporulation and genetic competence. Although spo0H is transcriptionally regulated by the key regulatory device that controls sporulation initiation, the Spo0 phosphorelay, there is considerable evidence implicating a mechanism of post-translational control that governs the activity and concentration of sigmaH. Post-translational control of spo0H is responsible for the reduced expression of genes requiring sigmaH under conditions of low environmental pH. It is also responsible for heightened sigmaH activity upon relief of acid stress and during nutritional depletion. In this study, the ATP-dependent proteases LonA and B and the regulatory ATPase ClpX were found to function in the post-translational control of sigmaH. Mutations in lonA and lonB result in elevated sigmaH protein concentrations in low-pH cultures. However, this is not sufficient to increase sigmaH-dependent transcription. Activation of sigmaH-dependent transcription upon raising medium pH and in cells undergoing sporulation requires clpX, as shown by measuring the expression of lacZ fusions that require sigmaH for transcription and by complementation of a clpX null mutation. A hypothesis is presented that low environmental pH results in the Lon-dependent degradation of sigmaH, but the activity of sigmaH in sporulating cells and in cultures at neutral pH is stimulated by a ClpX-dependent mechanism in response to nutritional stress.

ATP-Dependent Proteases↗
PubMed1996

Expression of component desmosomal proteins in uterine endometrial carcinoma and their relation to cellular differentiation.

BACKGROUND: While the assessment of the malignancy of neoplasms is based on morphologic studies of cells and tissues, use of objective molecular markers is leading to a better understanding and more biologically meaningful classification of neoplasms. In recent years, changes in the expression of cell adhesion molecules, especially E-cadherin, catenin, and adenomatous polyposis coli (APC), in carcinomas have attracted the attention of researchers. However, little is known about desmosomes in the uterine endometrium or in endometrial carcinomas. In this study, we semiquantified the desmosomal components desmoplakin I and II and desmoglein, in tissue sections using confocal laser scanning microscopy (LSM), and examined their relationship to the pathological type, the occurrence of lymph node metastases, and the extent of myometrial invasion. METHOD: Frozen sections of 31 specimens of normal endometrium, 5 specimens of atypical hyperplasia, and 41 specimens of endometrial carcinoma were stained by the immunofluorescence method using antidesmoplakin I and II and antidesmoglein, and these markers were then semiquantified in tissue sections by LSM. RESULTS: The expression and location of desmoplakin I and II and desmoglein were similar, and their expression decreased with loss of differentiation. The expression was lower in cases of lymph node metastasis than in negative cases and was lower in the cases with > one-half myometrial invasion than in cases with < one-half myometrial invasion. CONCLUSIONS: Reduction of desmoplakin I and II and desmoglein expression may play an important role in the invasiveness and metastatic activity of human endometrial carcinoma. They can therefore be used as differentiation markers for endometrial carcinoma.

Biomarkers, Tumor↗