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PubMed1986

Intestinal metaplasia and its variants in the gastric mucosa of Portuguese subjects: a comparative analysis of biopsy and gastrectomy material.

The incidence and prevalence of intestinal metaplasia (IM) of three types were investigated in 1,041 endoscopic biopsy specimens collected from patients with gastric abnormalities in 1981 and 1982. Intestinal metaplasia was classified as type I (complete), type II (incomplete, sulfomucin-negative), or type III (incomplete, sulfomucin-positive). Intestinal metaplasia, found in 244 biopsy specimens (23%), was prevalent in gastric carcinoma (65%), compared with the incidence of 18.4 per cent in benign conditions. The sulfomucin-negative types I and II were more common than type III and were present in both benign conditions (98 per cent) and carcinoma (64 per cent). In contrast, type III IM was seen in only 12 per cent of IM-positive biopsy specimens, 90 per cent of which (26 of 29) were from patients with carcinoma. The high specificity of type III IM (98 per cent) might be acceptable for screening purposes, but its sensitivity of 36 per cent for gastric carcinoma is low. Two main factors would seem to account for the low sensitivity, as shown in the comparative analysis of IM types in gastrectomy specimens and the previous biopsy specimens from 93 patients: 1) sampling and 2) the association of type III IM with gastric carcinoma of the intestinal type but not with diffuse gastric carcinoma. The data thus confirm a significant relation between incomplete sulfomucin-secreting IM (type III) and gastric carcinoma of the intestinal type (P less than 0.001). This variant of IM should be considered a risk factor, and its presence in a biopsy specimen should prompt close surveillance.

Adult↗
PubMed1986

Intestinal metaplasia of the gallbladder: a morphologic and immunocytochemical study.

The morphologic spectrum of intestinal metaplasia was studied in 49 gallbladders that had been excised because of cholelithiasis. Based on the absence or presence of endocrine cells, the cases of intestinal metaplasia were arbitrarily divided into two groups. The gallbladders from the first group (26 cases) contained isolated or small clusters of mature goblet cells, while those from the second group (23 cases), in addition to the goblet cells, contained argyrophil and argentaffin cells and, less frequently, Paneth cells and gland-like structures similar to colonic crypts. Pseudopyloric glands and superficial gastric-type epithelium were present in both groups. Argyrophil cells outnumbered argentaffin cells by a ratio of 4 to 1. By immunocytochemical methods serotonin-containing cells were found to be the most common endocrine cells. Other endocrine cells showed immunoreactivity for somatostatin, cholecystokinin, gastrin, and pancreatic polypeptide. The presence of gut endocrine cells and Paneth cells in the pseudopyloric glands suggests that these glands are also an integral component of intestinal metaplasia of the gallbladder. The findings support the hypothesis that cholelithiasis induces the appearance of a stem endodermal cell that, in turn, may differentiate into cells with mature intestinal or gastric phenotypes.

Adult↗
PubMed1979

Tritiated thymidine autoradiographic study on histogenesis and spreading of intestinal metaplasia in human stomach.

The non-diseased portions of the antral mucosa of patients suffering from gastric cancer or ulcer were biopsied. The biopsy specimens were then labelled with 3H-thymidine in vitro, and distribution of the labelled epithelial cells in the normal pyloric and in the intestinalized mucosa was studied with autoradiography, and modes of histogenesis and spreading of the intestinal metaplasia were studied, and kinetic characteristics of the intestinalized mucosa were discussed. In the normal pyloric mucosa, the labelled cells were confined to the isthmus region (the middle one-third level of the mucosa), indicating that the surface epithelial and the pyloric glandular cells are normally replaced from the isthmus region. On the other hand, a zone of the labelled cells was found at the lower one-third level in the intestinalized mucosa. The absorptive and the goblet cells in the intestinalized mucosa appear to be renewed by about 70 hours in a fashion similar to that of the small intestine. Microscopic and autoradiographic analysis of the antral mucosa in the course of intestinalization indicates that the intestinal metaplasia begins in the isthmus region of the pyloric glandular tubules of an intact mucosa unaffected by gross injury through transformation of the generative cells from a pyloric to an intestinal pattern. This permits the pyloric lining cells to be replaced with intestinal villous cells and also permits the generative cell zone of the intestinal tubules to shift from the isthmus to the base of the gland until the process is complete. The downward shift of the intestinal tubules occurs in a framework of one of the branched pyloric glands and other glands disappear, resulting in a change of mucosal architectures of the antrum from a branched to a simple tubular gland. The intestinal metaplasia spreads in the mucosa through multi-focal (and sporadical) transformation of the neck generative cells in individual glandular tubules.

Adult↗
PubMed1979

Loss of differentiation in intestinal metaplasia in cancerous stomachs. A comparative morphologic study.

229 stomachs resected for duodenal and gastric ulcer and carcinoma were examined with special regard to the morphological and histochemical pattern of intestinal metaplasia (IM). The results of qualitative and semiquantitative studies were analysed statistically. Whereas duodenal and gastric ulcer cases are best discriminated by the presence or absence of IM, the strongest discriminating factor between carcinoma and gastric ulcer is the content of goblet cells in metaplastic crypts. Metaplastic crypts lined exclusively with goblet cells producing sulfated acid glycoproteins could be identified in more than one third of the cancer cases. The increase in goblet cells coincides with a loss of the more differentiated cells in the metaplastic glands, such as enterocytes, APUD cells, or Paneth cells. This "enterocoli metaplasia" seems to be specific for cancer bearing mucosa and occurs more often in cancer of intestinal type; it may represent a form of a derepressive dedifferentiation. The significance of enterocoli metaplasia as a premalignant lesion remains to be elucidated.

Adult↗
PubMed1982

Simple alkaline treatment induces intestinal metaplasia in the stomach of rats.

By infusing caustic soda (NaOH) into the stomach of rats, the gastric mucosa fell off and regeneration could be induced. In 18 of 26 rats, intestinal metaplasia associated with goblet cells was observed in the regenerative epithelium. Recently, induction of intestinal metaplasia by weak carcinogenic agents are reported with some emphasis on its precancerous meaning. However, our results suggest that, as intestinal metaplasia can be induced by a benign process of regeneration, it is not directly related with carcinogenesis.

Animals↗
PubMed2002

Squamous metaplasia of endometrium after uterine artery embolization for symptomatic leiomyomata.

Uterine artery embolization (UAE) is frequently performed for symptomatic leiomyomata. There have been no reports of squamous metaplasia of endometrium after such a procedure. Squamous metaplasia of endometrium is often associated with endometrial hyperplasia and carcinoma. In our patient the disorder was diagnosed after UAE. This is the second such case we have encountered. In view of the association of squamous metaplasia with endometrial hyperplasia and carcinoma, a history of recent UAE must be considered in evaluating a patient with this finding, particularly on a biopsy specimen.

Embolization, Therapeutic↗
PubMed2002

[Metaplasia and high grade CIN. Diagnostic difficulties].

Squamous metaplasia of cervix represents the physiologic process of transformation of eversed glandular tissue at external orifice by a malpighian tissue. Primarily undifferentiated and immature, the epithelium progressively becomes differentiated and takes glycogen. In a high grade CIN the normal squamous epithelium is replaced by an undifferentiated tissue comporting basal cells with nuclear atypias. When cellular abnormalities are not marked, differential diagnosis exists with immature metaplasia. Cytology with suspicion of squamous intraepithelial lesion is sometimes followed by a diagnosis of high grade CIN on biopsy, but conisation reveals a metaplasia.

Biopsy↗
PubMed1999

Squamous metaplasia of the bladder: findings in 14 patients and review of the literature.

We have documented the data of squamous metaplasia of the bladder in 14 patients who had undergone cystoscopies for different reasons. In two biopsies, there were marked keratinization and cellular atypia. One of these two subjects was diagnosed as squamous carcinoma of the prostate and transitional cell carcinoma of the bladder. The lesions of 8 female patients were on the trigone and evaluated as normal anatomical variants due to hormonal changes. Three of them were remarkable because of recurrent urinary infections. Apart from the two male patients with squamous cell carcinoma of the prostate the two male patients with current squamous metaplasia have been following up. In this study, we have also reviewed the relationship between squamous metaplasia, infection and malignancy.

Adult↗
PubMed2003

Helicobacter pylori infection and high dietary salt independently induce atrophic gastritis and intestinal metaplasia in commercially available outbred Mongolian gerbils.

Risk factors for development of gastric adenocarcinoma include high dietary salt and Helicobacter pylori infection. Few animal models exist for the laboratory investigation of these factors. We examined gastric pathology resulting from H. pylori infection and high dietary salt as independent variables in commercially available, outbred Mongolian gerbils. Gastric adenocarcinoma and its precursor lesion, intestinal metaplasia, have been previously reported in inbred Mongolian gerbils (MGS/Sea) infected either with clinical isolates of H. pylori or with the strain ATCC 43504. In contrast, we utilized outbred gerbils [Crl:(MON)] infected with the Sydney strain of H. pylori. After 37 weeks, five of five infected animals had atrophic gastritis and intestinal metaplasia. These lesions were similar in description and time of appearance to the lesions reported in inbred gerbils. Atrophic gastritis and intestinal metaplasia also developed in six of six uninfected, outbred gerbils fed a 2.5% salt diet for 56 weeks. In contrast to the H. pylori-infected animals, these lesions were present without concurrent gastric inflammation. The outbred Mongolian gerbil therefore provides an excellent animal model for the study of several gastric cancer risk factors.

Animals↗
PubMed2003

2,6-dichlorophenyl methylsulphone induced behavioural impairments in rats and mice in relation to olfactory mucosal metaplasia.

2,6-Dichlorophenyl methylsulphone (2,6-diClPh-MeSO2) induces persistent olfactory mucosal metaplasia and a strong glial fibrillary acidic protein increase in the olfactory bulb of mice. Furthermore, 2,6-diClPh-MeSO2 gives rise to a long-lasting hyperactivity along with an impaired radial arm maze performance. To study cause-effect relationships, olfactory mucosal histopathology, glial fibrillary acidic protein induction and neurobehavioural deficits were re-examined in mice and rats of both sexes given a single intraperitoneal dose of 2,6-diClPh-MeSO2 (16 and 65 mg/kg). There was a clear difference in the character of the olfactory mucosal lesions in the two species. In mice, an extensive metaplasia characterised by severe fibrosis, cartilage and bone formation accompanied with large polyps filling the nasal lumen was confirmed. In rats, a dose-dependent weak metaplasia with patchy loss of olfactory epithelium was observed three weeks after dosing, preferentially at the dorsal meatus, nasal septum, and the tips of the middle ethmoturbinates. Large areas of intact olfactory epithelium remained in all animals, particularly in the low dose rats. In both species, 2,6-diClPh-MeSO2 gave rise to significantly increased motor-activities, impaired performance in the radial arm maze, and glial fibrillary acidic protein-induction. Only rats showed hyperactivity at the low dose. Performance in the Morris water maze was unaffected in rats of both sexes indicating that a general impairment in spatial learning could not be supported. We propose that the observed hyperactivity and radial arm maze acquisition deficits originated from a direct effect of 2,6-diClPh-MeSO2 in the brain rather than being a consequence of the olfactory mucosal lesion.

Animals↗
PubMed1998

Overexpression of p53 in different subtypes of intestinal metaplasia and gastric cancer.

p53 immunostaining was evaluated in cancerous epithelia and adjacent intestinal metaplasia of 135 gastric cancer specimens. The differential p53 overexpression in different subtypes of intestinal metaplasia and gastric cancer suggests that type III intestinal metaplasia is the commonest lesion in dysplasia-carcinoma transition, particularly in the intestinal type of gastric cancer.

Humans↗
PubMed2001

Her-2/neu gene amplification, elevated mRNA expression, and protein overexpression in the metaplasia-dysplasia-adenocarcinoma sequence of Barrett's esophagus.

SUMMARY: The importance of alterations of the Her-2/neu oncogene in the tumorigenesis of Barrett's adenocarcinoma (BCA) is discussed controversially. In the present study, we evaluated for the first time the Her-2/neu status in the metaplasia-dysplasia-adenocarcinoma sequence of BCA simultaneously at the DNA, mRNA, and protein level using resection specimens of 25 patients. The locus-specific Her-2/neu gene status was quantified by performing fluorescence in situ hybridization, and information about the ploidy status of chromosome 17 was obtained. Tissue sections from the same areas were used for quantitative RT-PCR (TaqMan RT-PCR) of laser-microdissected tumor cells and for immunohistochemistry to quantify Her-2/neu mRNA and oncoprotein expression. Her-2/neu gene amplification was observed in 35% of BCA, and all of these samples showed strong overexpression of both mRNA and oncoprotein. A polysomy 17 without Her-2/neu gene amplification was observed in 52% of BCA, showing a normal or moderately elevated mRNA expression and no or weak immunopositivity. From 13 areas of high-grade dysplasia (HGD) we found four to be amplified for the Her-2/neu locus, whereas five showed a polysomy 17. All four samples of HGD areas with Her-2/neu gene amplification displayed mRNA and strong oncoprotein overexpression; however, lower mRNA levels were seen than in the amplified BCA areas. None of the samples with low-grade dysplasia (LGD) showed a locus-specific Her-2/neu amplification, but polysomy 17 was present in four of eight cases. No changes were detected in BCA-associated intestinal metaplasia and squamous epithelium. In summary, only a locus-specific Her-2/neu gene amplification was associated with strong mRNA overexpression and strong membranous Her-2/neu immunostaining in BCA and HGD. A chromosome 17 polysomy, as found in the majority of BCA, led to no or weak mRNA overexpression and no or weak immunopositivity. In the metaplasia-dysplasia-adenocarcinoma sequence, a chromosome 17 polysomy without Her-2/neu gene amplification was already present in LGD. This may be a result of an early polyploidization, preceding the later genetic events, such as Her-2/neu gene amplification in HGD and BCA.

Adenocarcinoma↗
PubMed2004

Gastric PDX-1 expression in pancreatic metaplasia and endocrine cell hyperplasia in atrophic corpus gastritis.

The homeodomain transcription factor PDX-1 plays a key role in endocrine and exocrine differentiation processes of the pancreas. PDX-1 is also essential for differentiation of endocrine cells in the gastric antrum. The role of PDX-1 in the pathogenesis of endocrine cell hyperplasia and pancreatic metaplasia in corpus and fundus gastritis has not been evaluated. By immunohistochemistry and double-immunofluorescence, we investigated the expression of PDX-1 in 10 tissue specimens with normal human gastric mucosa, nonatrophic and atrophic gastritis and in pancreatic metaplasia, respectively. In normal corpus mucosa and in nonatrophic corpus gastritis, PDX-1 was mainly absent. In pancreatic metaplasia, PDX-1 was found in metaplastic cells and in adjacent gastric glands. In contrast to normal gastric corpus mucosa, PDX-1 could be strongly detected in the cytoplasm of the parietal cells surrounding metaplastic areas. Furthermore, PDX-1 expression was found in hyperplastic endocrine cells and in the surrounding gastric glands in chronic atrophic gastritis. Hyperplastic endocrine cells coexpressed the beta-subunit of the gastric H,K-ATPase. We conclude that PDX-1 represents a candidate switch factor for glandular exocrine and endocrine transdifferentiation in chronic gastritis and that an impaired parietal cell differentiation might play a key role in disturbed gastric morphogenic processes.

Adult↗
PubMed2002

Helicobacter pylori eradication therapy improves atrophic gastritis and intestinal metaplasia: a 5-year prospective study of patients with atrophic gastritis.

AIM: : To investigate the effect of the eradication of Helicobacter pylori on histological gastritis. METHODS: : Twenty-six patients with moderate to severe atrophy received successful eradication therapy of H.pylori. Four patients dropped out and 22 were followed up prospectively for 5 years. The grades of gastritis were estimated from gastric biopsy specimens. The grade of intestinal metaplasia was also evaluated by dye-endoscopy using methylene blue (methylthioninium chloride). The serum levels of pepsinogen, gastrin and anti-parietal cell antibody were also determined. RESULTS: : The grades of atrophy decreased in patients with successful eradication therapy in the gastric corpus (before vs. 5 years after eradication, 2.09 +/- 0.15 vs. 0.91 +/- 0.17; P < 0.01) and in the antrum (2.14 +/- 0.17 vs. 1.36 +/- 0.17; P < 0.01). The levels of intestinal metaplasia were also decreased in the corpus (0.91 +/- 0.24 vs. 0.50 +/- 0.16; P < 0.05) and in the antrum (1.41 +/- 0.20 vs. 1.00 +/- 0.16; P < 0.05), which was also demonstrated by the methylene blue (methylthioninium chloride) staining method (33.4 +/- 8.2% vs. 23.0 +/- 6.5%; P < 0.05). The improvement of corpus atrophy correlated well with the high serum level of pepsinogen I (P = 0.005), but showed no correlation with the levels of anti-parietal cell antibody. CONCLUSIONS: : These results suggest that gastric atrophy and intestinal metaplasia are reversible events in some patients.

Adult↗
PubMed1995

Retinoic acid provokes metaplasia of epithelium formed in vitro by adult human epidermal keratinocytes.

A striking effect of retinoids is their ability to alter cell fate during development. The mucous metaplasia produced by treating chick embryo skin in organ culture with retinoic acid is a classical example of this property. It has been impossible so far to demonstrate that retinoids are able to provoke metaplasia of adult keratinocytes grown in vitro, although these agents have been shown to block terminal epidermal differentiation, to induce increased synthesis of mucopolysaccharides, and to induce the ectopic expression of K19 and K13 keratins. Our previous work showed that adult human epidermal keratinocytes grown on dermal equivalents at the surface of a culture medium containing physiological amounts of retinoids form a normal keratinized epidermis, while when excess retinoic acid is added to the culture medium, keratinization is prevented but stratification is not. Here we show that the distribution of tissue- and differentiation-stage-specific markers in retinoic acid-treated epithelium is similar to that of the oral mucosa. Moreover, when the excess retinoic acid is removed, a new epithelium is formed beneath the "old" one and this epithelium displays an epidermal orthokeratinized phenotype, whereas the "old" epithelium remains unchanged. This phenomenon of "partial reversibility", as well as the mutually exclusive distribution of the markers of the two alternative routes of differentiation, demonstrate that retinoic acid is indeed able to provoke metaplasia of adult epidermal keratinocytes.

Adult↗
PubMed2000

Effects of subtotal resection of the fundus on development of intestinal metaplasia induced by X-ray irradiation in Donryu rats.

Eight-week-old male Crj:Donryu rats underwent subtotal resection of the fundus and X-ray irradiation. Six months later the animals were autopsied and examined for intestinal metaplasia. The numbers of alkaline phosphatase-positive foci with the two treatments in combination were significantly increased, compared to the operation alone and non-treatment groups. Histologically assessed intestinal metaplasia was also increased in the combined treatment group. In conclusion, subtotal resection of the fundus combined with X-ray irradiation is an effective induction protocol for intestinal metaplasia.

Alkaline Phosphatase↗
PubMed1996

Ultrasound-guided hysteroscopic management of endometrial osseous metaplasia.

In the past, most cases of osseous metaplasia of the endometrium were diagnosed following removal of bone from the endometrium by dilatation and curettage and frequently subsequently treated by hysterectomy. Nowadays, management involves a suggested diagnosis by transvaginal ultrasound examination, confirmation by hysteroscopy and hysteroscopic removal of ectopic intrauterine bone. This is usually carried out under laparoscopic guidance. However, the degree of visual control provided by combined transabdominal and transrectal ultrasonography may prove sufficiently accurate for hysteroscopic guidance. In this report we describe a case of endometrial osseous metaplasia successfully managed by ultrasound-guided hysteroscopy. The advantages of our approach include reduced invasiveness, reduced costs and simultaneous visualization of the abdominal and intrauterine cavities. One limitation, however, is represented by the greater operator dependence of ultrasound guidance as compared to laparoscopy, the former requiring extensive training and state-of-the-art equipment. We suggest that ultrasound guidance for hysteroscopic removal of extensive osseous metaplasia may represent a potentially safer and more effective alternative to laparoscopy and would therefore encourage further clinical evaluation of this technique.

Adult↗
PubMed2001

Choroid plexus papilloma with osseous and adipose metaplasia.

Rare cases of osseous and chondroid metaplasia in choroid plexus papillomas have been described. We report a case of left lateral ventricular choroid plexus papilloma presenting in a 25-year-old man. The tumor demonstrates prominent calcification with associated osseous metaplasia and a region of adipose metaplasia, which has not been previously described in these tumors. There is no evidence of mucin in the papilloma on mucicarmine and alcian blue stains. A MIB-1 labeling index (marker of cell proliferation) of 0.1% was noted. P53 immunoreactivity was not observed in the papilloma. Ann Diagn Pathol 5:43-47, 2001.

Adipose Tissue↗