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At least 415 records · Page 23Linked to original sources
PubMed2002

Expression of apoptosis-related proteins in Barrett's metaplasia-dysplasia-carcinoma sequence: a switch to a more resistant phenotype.

Barrett's esophagus, or columnar-lined esophagus (CLE), is a premalignant disorder in which the stratified squamous epithelium is replaced by metaplastic epithelium. To gain more insight into the process of carcinogenesis in CLE, we studied several factors involved in the apoptotic pathway in biopsies with gastric metaplasia (GM), intestinal metaplasia (IM), dysplasia, and/or adenocarcinoma. Immunohistochemistry was performed for Fas, Bcl-2, Bax, Bcl-xl, inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). Fas staining was positive in the epithelium of all biopsies from patients with CLE but negative in normal gastric mucosa. Fas staining was positive in all tumor cells of the 8 cases containing adenocarcinoma. Bcl-2 was positive in lamina propria immune cells of all specimens. Bax staining was positive in the epithelium of all biopsies, including tumor cells. Bcl-xl was positive in dysplasia and tumor cells, but negative in 8 of 17 biopsies containing IM. iNOS was positive in 20 of 21 biopsies with IM and in 4 of 8 dysplasia biopsies. COX-2 was positive in 7 of 8 adenocarcinomas. We conclude that the apoptotic balance in the transformation from IM to adenocarcinoma switches to an antiapoptotic phenotype because of increased Bcl-xl expression and decreased Bax expression. Fas can be used as a marker for the differentiation of gastric mucosa and metaplasia in the esophagus. iNOS is highly positive in CLE-associated intestinal metaplasia. COX-2 is negative in nonmalignant CLE. Therefore, pharmacologic inhibition of COX-2 activity is unlikely to be effective in the preventing CLE-associated adenocarcinoma. There was no clear correlation between iNOS expression and activation of proapoptotic and antiapoptotic genes.

Adenocarcinoma↗
PubMed2001

Osseous metaplasia as a cause of loss of extension after anterior cruciate ligament reconstruction.

We report a case of osseous metaplasia of an autologous anterior cruciate ligament (ACL) reconstruction that was implicated in blocking extension of the knee. Nonoperative treatment was unsuccessful. Arthroscopic excision of the ACL and osseous metaplasia abolished the fixed flexion deformity. The osseous metaplasia was an additional factor in causing the block to extension along with an anteriorly placed femoral tunnel, raising the question that nonisometry of the graft may be involved in the pathogenesis of the osseous metaplasia.

Adult↗
PubMed2002

Unsedated transnasal endoscopy accurately detects Barrett's metaplasia and dysplasia.

BACKGROUND: Unsedated transnasal upper endoscopy has a diagnostic yield comparable with that of sedated conventional upper endoscopy. The ability of transnasal upper endoscopy to detect Barrett's metaplasia or dysplastic change has not been systematically evaluated. The aim of this study was to assess the feasibility of transnasal upper endoscopy for surveillance of patients with Barrett's esophagus and to evaluate its histopathologic yield for Barrett's metaplasia and dysplasia. METHODS: Thirty-two patients with Barrett's esophagus were evaluated with conventional upper endoscopy and transnasal upper endoscopy. An effort was made to recruit patients known to have dysplasia. Quadrantic biopsy specimens were taken with standard (conventional upper endoscopy) and pediatric (transnasal upper endoscopy) biopsy forceps at procedures performed at least 1 week apart. Two blinded pathologists evaluated the specimens. RESULTS: Transnasal upper endoscopy detected Barrett's metaplasia histopathologically in 31 of 32 patients. Level of agreement for presence of dysplasia in biopsy specimens obtained between conventional upper endoscopy and transnasal upper endoscopy was excellent (k = 0.79). Interobserver agreement for dysplasia in specimens obtained by conventional upper endoscopy (k = 0.61) and by transnasal upper endoscopy (k = 0.61) were similar. Intraobserver agreement between conventional upper endoscopy and transnasal upper endoscopy biopsy specimens for dysplasia by pathologist 1 (k = 0.73) and pathologist 2 (k = 0.75) were also similar. No significant adverse effects were noted. CONCLUSIONS: Transnasal upper endoscopy is feasible and accurate for identification and histopathologic confirmation of Barrett's metaplasia with a histopathologic yield for dysplasia comparable with conventional upper endoscopy.

Adult↗
PubMed2003

Magnification chromoendoscopy for the diagnosis of gastric intestinal metaplasia and dysplasia.

BACKGROUND: The aim of this study was to define the reproducibility and accuracy of magnification chromoendoscopy for the diagnosis of lesions associated with gastric cancer (intestinal metaplasia and dysplasia). METHODS: A total of 136 patients with previously diagnosed lesions and 5 gastrectomy specimens were studied. Endoscopic examination was performed with a magnification endoscope after methylene blue (1%) spraying. According to differences in color and mucosal pattern, groups and subgroups of endoscopic images were defined, and biopsies taken (n = 462). Five endoscopists were asked to classify individually 2 endoscopic images per subgroup on 2 separate occasions. RESULTS: Three groups of endoscopic images were defined: nonmetaplastic, nondysplastic mucosa (I); metaplastic mucosa (II); and dysplastic mucosa (III). Ten subgroups were defined according to pit pattern: round small (IA), round and tubular small (IB), coarse round (IC), and course round pits with a straight pit (ID); blue irregular marks (IIA), blue round and tubular pits (IIB), blue villi (IIC), and blue small pits (IID); and loss of clear pattern, with depression (IIIA) or with slight elevation (IIIB). The kappa statistic for intraobserver agreement on the classification of endoscopic images in groups was 0.86; for interobserver agreement, it was 0.74. For classification into subgroups, kappa values ranged from 0.48 to 0.78. For 85% of the areas classified endoscopically as Group I (n = 146), no mucosal lesions or gastritis was described at histologic examination; for 83% of those in Group II (n = 198), intestinal metaplasia was found. Subgroups IIA and IIB were more often associated with complete intestinal metaplasia (62%), and IIC and IID with incomplete metaplasia (67%); in Group III (n = 118), dysplasia was diagnosed histopathologically in 33%. For the diagnosis of dysplasia, specificity was 81% (95% CI [77%, 85%]) and negative predictive value 99% (95% CI [99%, 100%]). CONCLUSIONS: Gastric endoscopic patterns with chromoendoscopy and magnification seem reproducible and valid for the diagnosis of lesions associated with gastric cancer. This procedure may improve the follow-up of individuals at high-risk of gastric cancer, at least for the exclusion of severe lesions.

Color↗
PubMed2001

Cell turnover in apocrine metaplasia of the human mammary gland epithelium: apoptosis, proliferation, and immunohistochemical detection of Bcl-2, Bax, EGFR, and c-erbB2 gene products.

Apocrine metaplasia is considered to be a benign lesion of human mammary epithelium. However, it is not known how apocrine differentiation develops, and whether there is a relationship with particular subtypes of mammary carcinoma. In order to investigate cell turnover in apocrine metaplasia, apoptosis was detected by terminal transferase nick-end-labelling, and Ki-67 was used as proliferation marker. Bcl-2, Bax, epidermal growth factor receptor (EGFR), and c-erbB2-encoded protein were detected by immunohistochemistry. The proliferative activity was low (<1%). Frequency and intraepithelial localization of apoptotic cells resembled those of normal mammary epithelium. Bax immunostaining was inconstant and weak, and Bcl-2 was not detectable in apocrine metaplasia. Immunoreactivity of the c-erbB2 gene product was membrane-bound and showed a moderate to strong intensity, whereas staining for EGFR was weak and inconsistent. When compared with normal breast epithelium, apocrine metaplasia shows a regular cell turnover at a low rate, although the expression patterns of regulatory proteins are clearly altered. Our data suggest that changes in the expression of Bcl-2 or c-erbB2 protein do not result in a significant imbalance of apoptosis and proliferation, and thus should not be interpreted as indicator for increased risk of neoplastic transformation.

Apoptosis↗
PubMed2004

Squamous cell carcinoma of the larynx with osteosarcoma-like stromal metaplasia.

Osseous or chondroid metaplasias are uncommonly found adjacent to laryngeal squamous cell carcinoma (SCC). These findings are less unusual in the spindle cell variant. We describe a moderately differentiated laryngeal SCC associated with osteocartilaginous metaplasia of the adjacent stroma which exhibited very similar morphologic changes and mitoses to an osteosarcoma. These uncommon findings can be more clearly understood if they are viewed as changes determined by the microenvironment of the tumour-host interface, as indicated in recent studies. Tumour cells seem able to regulate stromal development and differentiation via the release of growth factors and the induction of growth factor receptor expression on the cell surface. Irrespective of the limited number of reported cases, the association of SCCs of the larynx with osteocartilaginous metaplasia does not seem to support the adoption of treatments of choice that differ in approach to those for site- and stage-matched SCCs without osteocartilaginous metaplasia.

Carcinoma, Squamous Cell↗
PubMed1989

Incomplete intestinal metaplasia in the diagnosis of columnar lined esophagus (Barrett's esophagus).

To investigate the distribution and specificity of intestinal metaplasia (IM) in columnar lined esophagus (CLE), the authors reviewed biopsies of the hiatal hernia pouch (HHP) and esophagus from 17 patients with CLE (84 biopsies) and 10 controls (25 biopsies). The proximal margin of the gastric folds was used as an endoscopic landmark, corresponding to the gastroesophageal muscular junction (GEMJ). No biopsies obtained above the GEMJ in control patients showed columnar mucosa. No goblet cell metaplasia was seen in 21 biopsies of the HHP from patients with CLE or in 13 corresponding biopsies from controls. In contrast, alcian blue (AB) stains showed diffuse acid mucins in 3 of 21 biopsies of the HHP from patients with CLE and in 10 of 13 corresponding biopsies from controls, demonstrating that goblet cell metaplasia clearly distinguishes biopsies of CLE from the HHP (P less than 0.01), whereas small amounts of diffuse acid mucin on AB stains do not. IM evidenced by goblet cell metaplasia was frequently seen in biopsies only 2-3 cm above the GEMJ, and CLE was limited to that area in three patients, suggesting that the distal esophagus cannot be dismissed as a site for metaplastic and possibly premalignant mucosa. Adenocarcinoma was diagnosed during the course of the study in one patient with only 5 cm of columnar mucosa above the GEMJ.

Adult↗
PubMed1989

Hydrogen peroxide induces squamous metaplasia in a hamster tracheal organ explant culture model.

Reactive oxygen species have been shown in several systems to have a role in tumor promotion and carcinogenesis, although the exact mechanisms are yet to be elucidated. To investigate this further, the effect of hydrogen peroxide was studied in a hamster tracheal organ explant epithelial model. Hydrogen peroxide was added exogenously to tracheal explants maintained in defined serum free media at concentrations of 50, 100, 500 or 1000 microM daily for 1 h for a period of two weeks. The explants were then examined using scanning electron microscopy for evidence of morphologic alteration and for the development of squamous metaplasia. Control tracheal explants maintained in serum free media exhibited normal morphology (except for some decrease in the number of ciliated cells) and developed minimal squamous metaplasia after four weeks in culture. At concentrations of 500 and 1000 microM, hydrogen peroxide was toxic to the epithelium, resulting in complete necrosis of the epithelium within seven days. At concentrations of 50 and 100 microM, hydrogen peroxide treatment resulted within three weeks in the development of a significant degree of squamous metaplasia (covering 52 and 48.7%, respectively, of the surface epithelium). This effect could be negated by the exogenous addition of catalase. This model should be useful in the study of the early cellular events following oxidant injury that contribute to the development of squamous metaplasia.

Animals↗
PubMed2005

MAPK/AP-1 signal pathway in tobacco smoke-induced cell proliferation and squamous metaplasia in the lungs of rats.

Overwhelming evidence has demonstrated tobacco smoke (TS) is causally associated with various types of cancers, especially lung cancer. Sustained epithelial cell hyperplasia and squamous metaplasia are considered as preneoplastic lesions during the formation of lung cancer. The cellular and molecular mechanisms leading to lung cancer due to TS are not clear. Mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1) can be activated by various stimuli and play a critical role in the control of cell proliferation and differentiation. To date, information on the response of the MAPK/AP-1 pathway during hyperplasia and squamous metaplasia induced by TS is lacking. We therefore investigated the effects of TS on the development of epithelial hyperplasia and squamous metaplasia, regulation of MAPK/AP-1 activation, and expression of AP-1-regulated cell cycle proteins and differentiation markers in the lungs of rats. Exposure of rats to TS (30 mg/m(3) or 80 mg/m(3), 6 h/day, 3 days/week for 14 weeks) dramatically induced cell proliferation and squamous metaplasia in a dose-dependent manner, effects that paralleled the activation of AP-1-DNA binding activity. Phosphorylated ERK1/2, JNK, p38 and ERK5 were significantly increased by exposure to TS, indicating the activation of these MAPK pathways. Expression of Jun and Fos proteins were differentially regulated by TS. TS upregulated the expression of AP-1-dependent cell cycle proteins including cyclin D1 and proliferating cell nuclear antigen (PCNA). Among the AP-1-dependent cell differentiation markers, keratin 5 and 14 were upregulated, while loricrin, filaggrin and involucrin were downregulated following TS exposure. These findings suggest the important role of MAPK/AP-1 pathway in TS-induced pathogenesis, thus providing new insights into the molecular mechanisms of TS-associated lung diseases including lung cancers.

Animals↗
PubMed1999

Cytomegalovirus-induced syringosquamous metaplasia.

An unusual case of syringosquamous metaplasia of the eccrine ducts caused by cytomegalovirus (CMV) is presented. The patient was HIV positive and had extensive excoriation of the perineum and vulva. Biopsy revealed the presence of herpes simplex virus (HSV) inclusions in the necrotic exudate, a CMV vasculitis and extensive involvement of the eccrine ducts. In addition to containing typical CMV inclusions, the eccrine ducts showed proliferation and squamous metaplasia. Inclusions of HSV were not seen within the eccrine ducts by light microscopy or immunohistochemistry. The extensive proliferation with accompanying squamous metaplasia superficially can resemble an infiltrating squamous carcinoma, but this was not evident to a great extent in this case. To the best of our knowledge, our case represents the first of syringosquamous metaplasia of eccrine ducts caused by CMV infection.

AIDS-Related Opportunistic Infections↗
PubMed1996

Prevalence and significance of pancreatic acinar metaplasia at the gastroesophageal junction.

Pancreatic acinar metaplasia (PAM), defined as nodules of glandular tissue forming acini composed of cells with coarse apical eosinophilic granules, with or without mucous cells, was recently recognized in gastric mucosa, but its significance is not known. As part of a study on intestinal metaplasia at the gastroesophageal junction (GEJ), we evaluated the prevalence and clinical and histologic correlates of PAM in biopsy specimens from the gastroesophageal squamocolumnar junction. All adult patients having elective upper gastrointestinal endoscopy over a 6-month period were invited to participate. Clinical data and endoscopic findings were recorded. Biopsy specimens, obtained from both sides of the apparent squamocolumnar junction, were processed routinely and reviewed (without knowledge of the clinical data) to evaluate types of epithelium, types and degree of inflammation, and the presence of PAM. The presence or absence of PAM was then correlated with the other histologic findings and with the clinical and endoscopic data. The study comprised 155 patients (79 women, 76 men; 139 white patients, nine black patients, and seven patients of other ethnic groups). Their mean age was 52 years (range: 18-89 years). PAM was present in 37 patients (24%). PAM was not associated with any of the reported symptoms, endoscopic evidence of esophagitis or columnar epithelium in the distal esophagus, or any of the histologic features evaluated, including active esophagitis, intestinal metaplasia at the GEJ, active and chronic gastritis, intestinal metaplasia in the stomach, and Helicobacter infection. Although PAM is present in a considerable proportion (24%) of patients with mucosal biopsy specimens from the squamocolumnar junction, it appears to be an incidental finding unrelated to clinical or histologic abnormalities. We therefore suggest a congenital, rather than an acquired, origin for this entity.

Adult↗
PubMed1995

Helicobacter pylori infection and gastric metaplasia in the duodenum in China.

Biopsy specimens from antral and duodenal mucosa were obtained from 64 patients with active duodenal ulcer and from 78 with nonulcer dyspepsia. Gastric metaplasia in the duodenal bulb was more frequent in patients with duodenal ulcer (82.5%) than in patients with dyspepsia and duodenitis (53.1%) or in patients with dyspepsia without duodenitis (34.5%). Helicobacter pylori infection in the duodenal bulb was found more often in patients with moderate to severe gastric metaplasia (62.3%) than in patients with mild gastric metaplasia (20%). Therefore, patients from a developing country, China, showed the same relationship between duodenitis, gastric metaplasia, duodenal colonization with H. pylori, and duodenal ulcer previously demonstrated in developed countries.

Adolescent↗
PubMed2000

Sulfomucins in Helicobacter pylori-associated chronic gastritis in children: is this incipient intestinal metaplasia?

BACKGROUND: Little is known about early stages of intestinal metaplastic in chronic gastritis. The purpose of this study was to determine the presence of sulfated mucosubstances hence most probably intestinal metaplasia, in isolated cells of surface gastric pits, and glands in pediatric patients with Helicobacter pylori-associated chronic gastritis. METHODS: Participants were nine patients (nine different biopsies; mean age 11.5 years, range 3-16 years) with sulfomucin-containing cells evident in the gastric biopsy specimen. Eight of the patients were selected from a group of 15 patients with histologically documented H. pylori-associated chronic gastritis in whom the utility of the Sydney system was being tested. RESULTS: Symptoms and endoscopic findings of H. pylori-associated chronic gastritis were the same regardless of the presence or absence of sulfomucin-containing cells. On hematoxylin and eosin stained tissues, neither intestinal metaplasia nor atrophy was apparent. However, periodic acid-Schiff (PAS)-alcian blue (pH 1.0) stain revealed the presence of sulfated mucosubstances in isolated cells of gastric pits and glands in the nine patients. CONCLUSIONS: This finding may represent a "minimal" form of incomplete intestinal metaplasia (type III). Because the nine patients had been untreated, the change is probably reversible. Two follow-up biopsies in patients in whom H. pylori had been treated and eradicated showed absence of sulfated mucins. Although these findings cannot be regarded as fully developed type III intestinal metaplasia, it is possible that left untreated, the alteration may persist and evolve into some other complication. This conclusion justifies follow-up of these patients.

Adolescent↗
PubMed1996

Immunolocalization of keratan sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate in periprosthetic breast capsules exhibiting synovial metaplasia.

The distribution of various proteoglycans and basement membrane components within 10 breast capsules with synovial metaplasia was assessed immunohistochemically. Immunoreactive keratan sulfate and chondroitin-4-sulfate were present in many of the synovial metaplasia lining cells, suggesting active secretion of these proteoglycans into the intraprosthetic space. In contrast, chondroitin-6-sulfate was confined to the extracellular matrix of the underlying supporting fibrous capsule. Type IV collagen and laminin were not associated with the synovial metaplasia lining, thus confirming the absence of a basement membrane, as previously indicated by morphologic analysis. As with tendon reconstruction, the development and maintenance of a synovial metaplasia lining that secretes lubricating factors such as proteoglycans may be beneficial for decreased capsular contracture.

Breast↗
PubMed2003

Differential protein analysis of spasomolytic polypeptide expressing metaplasia using laser capture microdissection and two-dimensional difference gel electrophoresis.

Full analysis of cellular protein constituents is a valuable tool in the evaluation of tissues. Traditional methods of evaluation, however, are time-consuming and difficult to reproduce. Two-dimensional difference gel electrophoresis (2D-DIGE), a recently developed proteomic system, affords the ability to compare and evaluate protein extracts from multiple sources. Coupled with laser capture microdissection (LCM), this technology is a powerful tool in comparing the protein profiles of separate pure cell populations. Proteins are labeled in vitro with reactive cyanine dyes that fluoresce at differential wavelengths, and after comigration on two-dimensional gels, differing protein populations become apparent. The unique aspect of this technology is the ability to identify and quantify proteins from separate preparations without issues of gel-to-gel differences. These techniques coupled with the systems for robotic acquisition of specific spots on the gel, tryptic digestion, and MALDI mass spectrometry permit identification of proteins differentially expressed in two pure cell populations. The authors used these new technologies to analyze the protein constituents of spasmolytic polypeptide expressing metaplasia (SPEM), a gastric mucosal metaplasia (fundic antralization or pseudopyloric metaplasia) that develops in the atrophic fundus mucosa of mice infected with Helicobacter felis and in humans infected with Helicobacter pylori. In addition, SPEM has been identified in the atrophic mucosa surrounding a high percentage of gastric adenocarcinomas and may represent a precursor lineage of malignancy. This technology recognized 28 differentially expressed proteins between SPEM and surface cells. Identification of novel SPEM-related proteins would allow the development of new immunohistochemical antibodies to further study this important metaplasia.

Animals↗
PubMed2001

A postfundoplication study on Z-line appearance and intestinal metaplasia in the gastroesophageal junction.

The purpose of this study was investigate the Z-line appearance by using a previously proposed classification, the ZAP classification, and to investigate the prevalence of intestinal metaplasia in the Z-line, among fundoplicated patients. Sixty patients, who had undergone fundoplication 2 to 17 years earlier, were included in the study. The prevalence of intestinal metaplasia was 20%. Intestinal metaplasia was found to be associated with age, more than 10 years of symptoms of gastroesophageal reflux disease preoperatively, tongues of columnar epithelium in the distal esophagus, carditis, and ZAP grade. ZAP grade, furthermore, was associated with male gender and more than 10 years of symptoms of gastroesophageal reflux disease preoperatively. Among patients with intestinal metaplasia, different ZAP grades can indicate different etiologic factors. Even among patients undergoing fundoplication (i.e., patients with an anatomically altered gastroesophageal junction), the ZAP classification is a feasible tool to characterize the Z-line appearance. The ZAP classification could prove valuable in selecting patients for follow-up treatment.

Adult↗
PubMed2002

Symptomatic nephrogenic metaplasia of ureter: a morphologic and immunohistochemical study of four cases.

Nephrogenic metaplasia of the bladder and urethra has been the subject of extensive studies in recent years. However, information about ureteral involvement is still limited because of the rarity of the lesion. We described four cases of nephrogenic metaplasia of the ureter. They occurred in two men and two women whose ages ranged from 46 to 69 years. Three patients had stones, and one had multiple episodes of cystitis and chronic pyelonephritis. The lesions led to ureteral obstruction that in two patients was radiographically suspicious for carcinoma. Microscopically, three lesions were composed of tiny mucin-containing microcysts and medium-sized tubular structures lined by cuboidal cells that showed cytologic atypia characterized by enlarged vesicular nuclei and prominent nucleoli. However, there were no mitotic figures. Two lesions invaded the full thickness of the wall of the ureter and exhibited an infiltrative growth pattern highlighted by cytokeratin stains. The remaining two lesions were confined to the lamina propria. The cells of nephrogenic metaplasia were immunoreactive to cytokeratin 7 and AE1-AE3. They lacked reactivity for monoclonal and polyclonal CEA and p53. The MIB-1-labeling index was <5%. The cytologic atypia and infiltrative growth pattern of ureteral nephrogenic metaplasia should not be misinterpreted as evidence of malignancy. All four patients are alive and symptom free 8 months to 7 years after diagnosis.

Adenoma↗
PubMed1993

Influence of gastric pH modifiers on development of intestinal metaplasia induced by X-irradiation in rats.

The influence of gastric pH on intestinal metaplasia was examined in male Crj:CD(SD) rats. At the age of 5 weeks, animals were irradiated with two 10 Gy doses of X-rays to the gastric region at a 3-day interval (total 20 Gy), and 6 months after irradiation, received either secretin or histamine in silicon tubes for 2 months or had their bilateral submandibular salivary glands removed. The incidence of intestinal metaplasia in the fundus of animals after administration of secretin or histamine, or removal of the salivary glands were reduced, along with the pH values, as compared with values for rats given X-rays alone. In both the pyloric and the fundic gland mucosae, the numbers of alkaline phosphatase (ALP)-positive foci and type B metaplasias (intestinal crypts without Paneth cells) were also significantly decreased (P < 0.01). In a second experiment, started six months after irradiation, rats were kept on 1% sodium chloride (NaCl) diet for 6 months. Subsequent removal of salivary glands along with histamine treatment brought about a marked drop in pH and in numbers of ALP-positive foci after three and five days. The present results thus indicated that development and maintenance of intestinal metaplasia can be influenced by a decrease of pH value.

Animals↗