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Results for “Morphological Characterization”

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PubMed2000

Ultrastructural, immunocytochemical and flow cytometry study of mouse peritoneal cells stimulated with carrageenan.

In the present paper we performed a morphological characterization of mouse peritoneal cells stimulated in vivo for 24 h with carrageenan (CAR) and lipopolysaccharide (LPS) by ultrastructural and flow cytometry analysis. In all samples, the flow cytometry studies showed the presence of three major populations consisting of monocytes, macrophages and lymphocytes. A special recruitment of monocytes was detected in CAR-injected mice. Macrophages and monocytes from CAR-treated mice displayed a characteristic phenotype, with a larger number of cytoplasmic vacuoles and numerous membrane projections, as compared to the cells collected from LPS- and PBS-injected mice. The induction of vacuolization was also confirmed upon in vitro treatment with CAR for 15 min to 24 h. The in vivo CAR-induced vacuoles were not related to lipid storage as judged by the lack of lipidic labeling after imidazole treatment at the ultrastructural level. In order to investigate the acidic nature of the vacuoles we used acidothropic probes, Lysotracker Yellow (LY) and Acridine Orange (AO). CAR injection activated the ability of peritoneal cells to incorporate LY around 2-5 times higher than control cells. However, the AO incorporation was 10-fold lower in CAR-stimulated cells than in LPS-stimulated ones. It is possible that the increase in intracellular vacuolization observed in CAR-stimulated cells could be related to exocytosis, since in most vacuoles the inflammatory protein MRP-14 was immunolocalized. The presence of MRP-14 in the culture supernatant of adherent peritoneal cells from CAR-injected mice was further comfirmed by ELISA, suggesting the discharge of MRP-14 enriched vacuole contents in the extracellular medium. We concluded that the morphological characteristics of activated monocytes and macrophages may depend on the nature of the triggering stimuli. Our observations reflect different functional phenotypes of monocytes/macrophages after in vivo stimulation with inflammatory agents such as CAR and LPS.

Animals↗

PubMed1986

Origin and distribution of phrenic primary afferent nerve fibers in the spinal cord of the adult rat.

Previous studies from this laboratory have localized and morphologically characterized phrenic motor neurons in the rat spinal cord at light and electron microscopic levels. The present investigation used a modification of the TMB method for the retrograde transport of horseradish peroxidase (HRP) to describe at light microscope levels the origin and distribution of phrenic primary afferent axons in the adult rat spinal cord. Dry HRP crystals were applied to the central stump of the transected phrenic nerve in the neck to label spinal ganglion cell bodies and thus determine the levels of origin of afferent axons in the phrenic nerve. Camera lucida drawings were then made from serial sections through the appropriate spinal cord levels to determine the specific distribution of transganglionically labeled phrenic central axonal processes within the spinal cord. HRP-labeled phrenic primary neurons were observed in the C3 to C7 spinal ganglia. The camera lucida studies indicated that the transganglionically labeled central processes of phrenic primary afferent axons distributed into the dorsal horn at the C4 and C5 levels of the spinal cord. Furthermore, central processes distributing to C5 were more numerous than those that distributed to C4. Afferent axons were never seen in the dorsal horn at C3, C6, or C7. As spinal ganglion cells were labeled at C3 above and C6 and C7 below, it follows that central processes of phrenic afferent fibers descend and ascend in the dorsal columns of the spinal cord before distributing into the dorsal horn. Specifically, the labeled primary afferent axons and their collateral branches were found in the fasciculus cuneatus, and in laminae I, II, III, and IV of the dorsomedial aspect of the dorsal horn. The function of these central axonal processes is unknown, but based on a comparison of our morphologic data with previous physiological and anatomical studies, we suggest that phrenic afferent fibers may arise from proprioceptors (muscle spindles and Golgi tendon organs), nociceptors, or rapidly adapting mechanoreceptors (Pacinian corpuscles) within the diaphragm.

Afferent Pathways↗

PubMed1997

Evidence for inflammatory and secretagogue lipids in cyst fluids from patients with autosomal dominant polycystic kidney disease.

Advanced autosomal dominant polycystic kidney disease (ADPKD) is characterized morphologically by massive cyst enlargement, moderate interstitial infiltration with mononuclear cells, and extensive fibrosis. In patients affected by a common genotype (PKD1), it has been suggested that the progressive decline in renal function that transpires over a highly variable time course may be due to endogenous or exogenous epigenetic factors. We have postulated that a neutral lipid, discovered in human cyst fluid and stimulating the rates of transepithelial fluid secretion and cellular proliferation of renal epithelial cells in vitro may have a potential role in cyst growth and the progressive decline of kidney function. In this study, we used thin-layer chromatography (TLC) and high-performance TLC (HPTLC) to determine whether lipid extracts of human cyst fluid stimulated monocyte chemotaxis in vitro. Monocyte chemotactic activity, determined by the transmembrane migration of murine RAW 264.7 cells, was stimulated (delta 26.0 +/- 1.5 optical density units) by a lipid fraction less polar than sphingosine but more polar by TLC and HPTLC than 1-monooleoylglycerol. A high level of secretagogue activity was detected in this fraction (delta 0.336 +/- 0.022 microliter/cm2 1 hr) and to a lesser extent (delta 0.253 +/- 0.022 microliter/cm2/hr) in a neighboring fraction that encompassed the 1-monooleoylglycerol standard. Cyst fluid with undetectable secretagogue activity had a monocyte chemotactic-activity level only 18% as great as fluids with high levels of secretagogue activity. The secretagogue and chemotactic activities in TLC-HPTLC fractions were resistant to treatment with KOH, but both were diminished by HCl, borohydride, or periodate. Rat proximal tubule cultures incubated with oleate complexed with albumin elaborated secretagogue and chemotactic activities in the conditioned medium, with TLC-HPTLC mobility characteristics similar to the biologically active cyst fluid lipids. On the basis of these studies, we conclude that human cyst fluids harbor potent secretagogue and chemotactic lipids that may have a role in determining the functional course of ADPKD. On the basis of preliminary chemical characterizations, we suggest that the secretatogue and monocyte chemotactic activities of cyst fluid may reflect the action of lipid molecules of similar structure, the source of which may be renal epithelial cells.

Animals↗

PubMed1978

Visualization of small extracanalicular neurilemomas by metrizamide cisternographic enhancement.

Metrizamide (Amipaque) computerized tomography cisternography (CTC) provides a rapid, simple, and accurate radiographic modality of intrathecal enhancement for detecting and morphologically characterizing cerebellopontine (CP) angle masses. The technique is of especial value in masses greater than 1.5 cm that are not detected on intravenously enhanced computerized tomography. Metrizamide CTC was used in six patients with no CP angle mass and in four patients with acoustic neurilemomas.

Cerebellar Neoplasms↗

PubMed1997

Immunohistochemical and ultrastructural investigation of the human vestibular dark cell area: roles of subepithelial capillaries and T lymphocyte-melanophage interaction in an immune surveillance system.

BACKGROUND: The aim of the present study was to morphologically characterize the structure of the subepithelial blood vessels in the dark cell area of the human vestibular organs, and to determine whether immunocompetent cells such as macrophages and lymphocytes could be found around these small blood vessels. MATERIALS AND METHODS: All 31 surgical specimens (semicircular canals and utricles) were obtained from patients with vestibular schwannoma. Formalin fixed specimens were stained with hematoxylin and eosin (H&E), and with antibodies to von Willebrand Factor (vWF), leukocyte common antigen (LCA), and UCHL-1, and were examined with light microscope. Specimens fixed with glutaraldehyde were examined with a transmission electron microscope (TEM). OBJECTIVES: Subepithelial blood vessels stained positive for vWF. By TEM observation, these blood vessels were observed to be capillaries that consisted of non-fenestrated endothelium, occasional pericytes, and a basement membrane. They were usually accompanied by melanophages with a number of secondary lysosomes containing phagocytosed degraded melanosomes and lipid droplets. Moreover, melanocytes and their cell processes directly surrounded these subepithelial capillaries. The fact that cells which were positively stained with LCA and UCHL-1 were present both in the intra- and subepithelial layer of the specimens, and that by TEM the intra- and subepithelial mononuclear cells with a lymphoid appearance had clustered dense bodies in their cytoplasm, suggested that they were a population of T lymphocytes. CONCLUSIONS: Results suggested the possibility of a T lymphocyte-melanophage (macrophage) interaction, both originating from and harbored around subepithelial capillaries, which suggests the presence of an immune surveillance system in the human vestibular organs.

Adult↗

PubMed2000

Postnatal differentiation of efferent ductule epithelium in goats: a light microscopic and ultrastructural study.

Caprine efferent ductule epithelium contains ciliated and nonciliated cells. The latter cells are divided into three types: type II cells contain PAS-positive granules, type III cells contain PAS-negative vacuoles, and type I cells lack both granules and vacuoles (Goyal and Williams, Anat. Rec. 220:58-67). The objectives of this study are i) to determine when the epithelium differentiates into ciliated and nonciliated cells, ii) to determine when nonciliated cells acquire characteristics typical for type II and type III cells, and iii) to relate developmental changes in the epithelium with those in the testis. Testes and efferent ductules were examined at the light and electron microscopic levels in goats from 1-25 weeks of age. Efferent ductule epithelium contained ciliated and nonciliated cells as early as week 1. While ciliated cells were differentiated at week 1, differentiation of nonciliated cells did not occur until week > or =15. Differential features in ciliated cells included the presence of cilia at the apical border and an aggregation of mitochondria in the apical cytoplasm. Those in nonciliated cells included the presence of i) an endocytotic apparatus at week > or =15, ii) PAS-positive granules at week > or =15, and iii) PAS-negative vacuoles at week > or =25. The seminiferous tubules developed lumens at 12-15 weeks. Hence, while differentiation of ciliated cells occurred much before lumen formation in the seminiferous tubules, that of nonciliated cells coincided with, or occurred soon after, lumen formation, suggesting a role for testicular fluid contents in their differentiation. The goat efferent ductules can be characterized morphologically mature by 25 weeks.

Age Factors↗

PubMed1996

Induction of connexin43 and gap junctional communication in PC12 cells overexpressing the carboxy terminal region of amyloid precursor protein.

Previous studies have shown that PC12 cells overexpressing beta/A4 amyloid peptide display altered morphology characterized by pronounced membrane ruffling and extensive intercellular appositions. Having observed other cell types in which these features accompany increased connexin43 (Cx43) production and gap junctional communication, we examined Cx43 in normal and beta/A4-transfected PC12 cells. Studies of two beta/A4-transfected PC12 clones revealed an induction of Cx43 expression by Western blotting, intracellular and plasma membrane-associated Cx43 in some cells of cultures processed by immunofluorescence, dye-transfer between some cells microinjected with Lucifer Yellow, and gap junctions between cells examined by EM. Normal and vector-transfected PC12 cells exhibited none of these properties. Increased immunofluorescence in some clusters of beta/A4-transfected cells was also observed with a monoclonal antibody against connexin32. The results suggest that beta/A4 amyloid peptide may cause aberrant intercellular communication and gap junction formation through induction or increased expression of connexins in cells that are not normally coupled or only poorly coupled by gap junctions.

Amyloid beta-Protein Precursor↗

PubMed1997

Familial mixed congenital myopathy with rigid spine phenotype.

We describe a father and daughter with a rigid spine syndrome and proximal myopathy. The index patient was a 42-year-old man, who died from respiratory failure after a lifelong, slowly progressive proximal myopathy and a rigid spine phenotype. This was morphologically characterized by cytoplasmic bodies, increased desmin, features of reducing-body myopathy, and sarcoplasmic and intranuclear tubulofilamentous inclusions. These cases are characterized by an early onset and possibly autosomal-dominant inheritance, with associated complex structural hallmarks of both desmin-related and inclusion body myopathies. Together they may be defined as a complex mixed congenital myopathy with a rigid spine phenotype.

Adult↗

PubMed1997

Analysis of multiple mitochondrial DNA deletions in inclusion body myositis.

Inclusion body myositis (IBM) is a sporadic progressive myopathy, which is morphologically characterized by inflammatory cell infiltrates and rimmed vacuoles in muscle fibers. Mitochondrial changes are regularly present with ragged-red fibers showing deficiency of cytochrome c oxidase. In these muscle fiber segments, there is accumulation of mitochondria with mitochondrial DNA (mtDNA) deletions. There are different deletions in different muscle fibers. In this study, we have sequenced for the first time the multiple mtDNA deletions in muscle from four patients with IBM. The deletion breakpoints were sequenced from cloned polymerase chain reaction (PCR)-amplified mtDNA fragments. The sequencing was performed directly from the bacterial colonies used for cloning. Of 122 analyzed clones, 33 different deletions were identified. The majority of these have not previously been described. There was a marked predominance of deletion breakpoints in certain regions of mtDNA. These predominant breakpoint regions are similar to those described in other conditions with multiple deletions, such as autosomal dominant progressive external ophthalmoplegia (adPEO) and normal aging, but different from those described in diseases due to single deletions such as Kearns-Sayre syndrome and sporadic PEO. These findings indicate that common factors are involved in the development of multiple mtDNA deletions in IBM, adPEO, and aging.

Adult↗

PubMed1985

T-cell lymphoma following Hodgkin's disease.

Three patients initially diagnosed with Hodgkin's disease developed non-Hodgkin's lymphoma 1.5, 7, and 16 years later, respectively. Combined modality therapy had been employed in one patient; the other two had received combination chemotherapy. All three of the second neoplasms were morphologically characterized as peripheral T-cell lymphomas. Cell surface marker studies performed on two of these tumors confirmed their T-cell origin. Second lymphoproliferative malignancies are an increasingly recognized complication in patients with Hodgkin's disease. Further immunologic phenotyping is needed to more conclusively define the origin and frequency of occurrence of these tumors.

Adolescent↗

PubMed1993

Salivary duct carcinoma.

BACKGROUND: Salivary duct carcinoma (SDC) is a distinctive salivary gland neoplasm morphologically characterized by intraductal and infiltrating components. Most tumors occur in the major salivary glands and demonstrate a propensity for invasive growth with early regional and distant metastases. Therefore, SDC is regarded as a high-grade malignancy in the current classification of salivary gland neoplasms. METHODS: In an effort to identify clinically relevant prognostic features, we studied the clinicopathologic and immunohistochemical findings in 15 SDC, with ultrastructural evaluation of three tumors. RESULTS: Thirteen SDC occurred in the parotid gland, one in the Stensens duct, and one in the palate. Twelve patients were men (ratio of men to women = 4:1). Patients ranged in age from 39 to 81 years (mean = 59 years). Tumor size varied from 1.2 to 6.5 cm (mean = 3.1 cm). An intraductal component was identified in 10 of 14 primary SDC that made up 10% to 95% of the tumor. In three SDC a preexisting pleomorphic adenoma was identified. Immunohistochemical and electron microscopic evaluation showed the SDC to be composed entirely of ductal cells, and one tumor exhibited features of striated duct differentiation. CONCLUSIONS: SDC show a broader clinicopathologic spectrum than previously described. The tumor may arise in a pleomorphic adenoma. The proportion of intraductal and extraductal growth is variable and of prognostic significance. Although the majority of SDC behave in a high-grade fashion, those with a predominant intraductal component of greater than 90% (PID-SDC) and minimally invasive (< 8 mm) SDC in pleomorphic adenoma appear to have a more favorable prognosis.

Adenoma, Pleomorphic↗

PubMed2001

Estrogen and estrogen plus progestin act directly on the mammary gland to increase proliferation in a postmenopausal mouse model.

Hormone replacement therapy (HRT) with ovarian hormones is an important therapeutic modality for postmenopausal women. However, a negative side effect of HRT is an increased risk of breast cancer. Surgical induction of menopause by ovariectomy (OVX) in mice is an experimental model that may provide insights into the effects of hormone replacement therapy on the human breast. We have developed a mouse model of early and late postmenopausal states to investigate the effects of HRT on the normal mammary gland. The purpose of this study was to determine if HRT-induced proliferation was due to the direct action of the hormones on the mammary gland, or mediated systemically by hormones or growth factors produced elsewhere in the body. Estrogen (E) or E plus the synthetic progestin, R5020, were implanted directly into the mammary glands of early (1 week post OVX) and late (5 week post OVX) postmenopausal mice instead of administration by injection. We report that responses of early and late postmenopausal mice to implanted hormones were the same as those observed previously with systemically administered hormones. Implanted E conferred an enhanced proliferative response in the late postmenopausal gland characterized morphologically by enlarged duct ends. E+R5020 implants induced similar degrees of cell proliferation in both postmenopausal states but the morphological responses differed. Ductal sidebranching was observed in early postmenopausal mice, whereas duct end enlargement was observed in late postmenopausal mice. The differences in morphological response to E+R5020 in 5 week post OVX were associated with an inability of E to induce progesterone receptors (PR) in the late postmenopausal gland. The responses of the late postmenopausal glands to E and E+P were very similar to that observed previously in immature pubertal glands in ovary-intact mice. In pubertal mice, PR cannot be induced by E unless the mammary gland is pre-treated with EGF-containing implants. Similarly, herein pre-treatment of the late postmenopausal mammary gland with EGF-containing implants restored PR induction by E. Thus, EGF may determine the sensitivity of the mammary gland to E and E+P in late postmenopause and at puberty.

Animals↗

PubMed2000

RT-PCR analysis of the MOZ-CBP and CBP-MOZ chimeric transcripts in acute myeloid leukemias with t(8;16)(p11;p13).

The translocation t(8;16)(p11;p13) is associated with a subtype of acute monocytic leukemia (AML M5) characterized morphologically by erythrophagocytosis and clinically by a poor prognosis. The t(8;16) fuses the MOZ gene from 8p11 with the CBP (also named CREBBP) gene from 16p13. Previously published studies of MOZ and CBP rearrangements in t(8;16)-positive AML have used fluorescence in situ hybridization and Southern blot methodologies, whereas attempts to amplify and to analyze further the chimeric MOZ-CBP and CBP-MOZ transcripts by means of reverse transcriptase-polymerase chain reaction (RT-PCR) have largely been unsuccessful. In the only t(8;16) that has been described at the sequence level using RT-PCR, the CBP-MOZ fusion was found to be out-of-frame, suggesting that the reciprocal MOZ-CBP transcript is the essential one for leukemogenesis. We have developed an RT-PCR strategy that enables us to detect the MOZ-CBP as well as the CBP-MOZ fusions in the two AML M5 with t(8;16)(p11;p13) analyzed. In both leukemias, the combination of a MOZ forward and a CBP reverse primer amplified a strongly expressed 1,128 bp fragment (type I transcript) and a weakly expressed 415 bp fragment (type II transcript). In the type I transcript, nucleotide (nt) 3,745 of MOZ was fused in-frame with nt 284 of CBP, whereas in the type II transcript, nt 3,745 of MOZ was fused out-of-frame with nt 997 of CBP. Nested PCR with a combination of two forward CBP and two reverse MOZ primers amplified CBP-MOZ chimeric transcripts in both cases. Direct sequence analysis showed that nt 283 of CBP was fused in-frame with nt 3,746 of MOZ, that the initiation ATG codon of the CBP gene remained intact, and that there was no mutation or deletion in the part of the CBP gene included in the CBP-MOZ transcript. Thus, the data we present are not informative with regard to the question whether it is the MOZ-CBP or the CBP-MOZ transcript that is leukemogenic. The present RT-PCR method may be of value for rapid identification of the t(8;16) and also for further molecular genetic studies of the two fusion transcripts and their roles in leukemogenesis.

Acetyltransferases↗

PubMed1988

Dysmyelination in transgenic mice containing JC virus early region.

JC virus (JCV) causes the chronic human demyelinating disease progressive multifocal leukoencephalopathy. Because of host range restrictions, experimental models of JCV-induced demyelination have not been available. The restricted tropism of JCV infectivity has recently been overcome by the production of transgenic mice that contain the early region of JCV in all cells. This portion of the DNA encodes JCV T-antigens. These mice display a dysmyelinating phenotype, the severity of which is related to the level of JCV early region expression in brain. With the use of immunocytochemistry and in situ hybridization, we characterized morphologically myelin-specific and JCV gene expression in a severely affected strain of these mice. Our results suggest that expression of JCV T-antigens occurs predominantly in oligodendrocytes and is the primary cause of dysmyelination. Affected oligodendrocytes do not myelinate axons properly. However, they express myelin-specific genes and display some of the morphological phenotypes of early stages of myelination. A decreased ratio between levels of transcriptional and translational products of genes encoding the major structural proteins of central nervous system myelin was apparent. These results suggest that JCV T-antigens arrest the maturation of oligodendrocytes and inhibit the production of myelin. These results also demonstrate that JCV transgenic mice are a good model for investigating mechanisms of JCV-induced demyelinating lesions in progressive multifocal leukoencephalopathy.

Animals↗

PubMed1981

The ultrastructure of cultures from the Swarm rat chondrosarcoma.

When chondrocytes from the Swarm rat chondrosarcoma are isolated by trypsin and collagenase digestion and cultured in Petri dishes, they form a new extracellular matrix within 24 hours, with proteoglycan matrix granules and collagen fibrils. This rapid synthesis of new matrix, together with the biochemical and morphological characterization of the proteoglycans as typical of cartilage, demonstrates the value of these cultures as a model system for studies of synthesis, secretion, and organization of extracellular matrix.

Animals↗

PubMed1993

Cell biology of pulmonary neuroepithelial bodies--validation of an in vitro model. I. Effects of hypoxia and Ca2+ ionophore on serotonin content and exocytosis of dense core vesicles.

Pulmonary neuroendocrine (NE) cells including the innervated clusters of NE cells--neuroepithelial bodies (NEB)--are difficult to study because of their small numbers and diffuse distribution within the airway mucosa of the lung. We have previously reported a method for isolation and culture of NE cells from rabbit fetal using a combination of mechanical and enzymatic dissociation followed by gradient centrifugation. This method provides single cell suspension of mixed lung cells enriched in NE cells, particularly those originating from NEB. This study further validates our in vitro model by detailed morphologic characterization of cultured NEB cells using high resolution light microscopy, transmission and scanning electron microscopy, HPLC for detection of serotonin (5-HT), and molecular (Northern blot) analysis of mRNA encoding for 5-HT synthesizing enzymes, tryptophane hydroxylase, and aromatic L-amino acid decarboxylase. In addition the effects of hypoxia on NEB cells in vitro were investigated to define the role of these cells as possible airway chemoreceptors. Exposure of NEB cultures to hypoxia resulted in decreased intracellular content of 5-HT accompanied by increased exocytosis of dense core vesicles (DCV). The amount of 5-HT release correlated with the degree of hypoxia, suggesting modulation by ambient pO2 levels. The role of Ca2+ ions in exocytosis of DCV and 5-HT release from NEB cells was tested in experiments with Ca2+ ionophore (A23187). Exposure of cultures to 5 micrograms/ml of ionophore resulted in up to 40% reduction in 5-HT content of NEB cultures as well as increased exocytosis of DCV. Our overall findings are consistent with a view that NEB cells are chemosensory in nature and that Ca2+ signaling pathway is involved in stimulus-secretion coupling. Further refinements in cell separation and culture methodology are required before more detailed investigation of NEB cell membrane properties, signal transduction mechanisms, and intracellular signaling pathways can be carried out.

Animals↗

PubMed2004

Large cell neuroblastoma: a distinct phenotype of neuroblastoma with aggressive clinical behavior.

BACKGROUND: Among cases of undifferentiated and poorly differentiated tumors in the neuroblastoma (Schwannian stroma-poor) category, the authors histologically identified a group of rare tumors, known as large cell neuroblastomas (LCNs), that are composed of large cells with sharply outlined nuclear membranes and 1-4 prominent nucleoli. METHODS: Histologic and immunohistochemical features of LCN were characterized. Morphologic characteristics, clinical features, and MYCN status were compared between LCNs and conventional neuroblastomas documented in the files of two European centers (the Sir James Spence Institute of Child Health, Royal Victoria Infirmary, University of Newcastle, Newcastle upon Tyne, United Kingdom, and the Medical and Health Sciences Center, University of Pécs, Pécs, Hungary). RESULTS: Of 92 peripheral neuroblastic tumors (pNTs; including neuroblastoma [n = 81]; ganglioneuroblastoma, intermixed [n = 6]; and ganglioneuroblastoma, nodular [n = 5]), 7 (7.6%) qualified as LCN. All 7 LCNs were classified as having unfavorable histology (UH) according to the International Neuroblastoma Pathology Classification. The LCNs were composed of monomorphous undifferentiated neuroblasts and shared certain histologic features, such as a high incidence of high mitosis-karyorrhexis index and a low incidence of calcification, with other neuroblastomas in the conventional UH (c-UH) group. These features were significantly different from those of neuroblastomas in the conventional favorable histology (c-FH) group. On immunohistochemical analysis, LCN tumor cells were positive for neuron-specific enolase (5 of 5 cases), protein gene product 9.5 (5 of 5 cases), synaptophysin (5 of 5 cases), tyrosine hydroxylase (focally in 3 of 3 cases), and NB84 (3 of 5 cases) and negative for CD99. Patients with LCN and patients with c-UH disease had similar clinical features (diagnosis at age > 1 year, often with distant metastasis). The clinical features of these patients also were significantly different from those of patients with c-FH disease. Further analysis demonstrated that the LCN group was significantly different from both the c-UH and c-FH groups with respect to MYCN status (MYCN amplification, 4 of 5 vs. 3 of 17 vs. 8 of 17, respectively; P = 0.023) and survival rate (4-year expected survival, 0% vs. 71% vs. 17%, respectively; P < 0.01). CONCLUSIONS: Because of its unique clinicopathologic features, the authors propose that LCN be recognized as a distinct entity within the undifferentiated and poorly differentiated subtypes of the neuroblastoma category.

Child↗

PubMed2005

Loss of function of p16 gene and prognosis of pulmonary adenocarcinoma.

BACKGROUND: Stepwise progression of peripheral-type lung adenocarcinoma was characterized morphologically and was related to prognosis. Expression of the tumor suppressor gene p16 in pulmonary adenocarcinoma decreased, mainly as a result of aberrant methylation of the CpG islands of the promoter region. METHODS: Aberrant methylation status of the p16 promoter region, the expression of its product, and loss of heterozygosity (LOH) on 9p21 were examined in surgically resected lung specimens from 57 patients (28 males and 29 females) with peripheral-type lung adenocarcinoma measuring </= 2 cm in diameter. RESULTS: Aberrant methylation of the p16 promoter region, negative p16 protein expression, and LOH of the 9p21 region were detected in 40.4%, 50.9%, and 40.4% of tumor samples, respectively. The alterations of the p16 gene were associated with poor prognosis, and in particular the prognosis of patients with aberrant p16 methylation was significantly worse than that of patients without aberrant methylation. These alterations also were associated with morphologic classification into bronchioloalveolar carcinoma (BAC) and non-BAC adenocarcinoma. Both aberrant methylation and LOH of 9p21 were associated with negative protein expression, but the former was correlated more closely with loss of function than was the latter. Cases with both alterations were completely negative for expression of the p16 gene product. CONCLUSIONS: Aberrant methylation of the promoter region of the p16 gene and loss of expression of its product were in accord with the multistep progression of peripheral-type lung adenocarcinoma, and these alterations were associated closely with poor prognosis of the disease.

Adenocarcinoma↗