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PubMed2004

Expression of RUNX3 protein in human gastric mucosa, intestinal metaplasia and carcinoma.

BACKGROUND: Human runt-related transcription factor gene 3 (RUNX3) is considered as a possible candidate of tumour suppressor gene in human gastric carcinoma. MATERIALS AND METHODS: To investigate the RUNX3 protein expression in human gastric mucosa and carcinoma, we generated a polyclonal antibody, AS251, which recognized amino acid sequences from 251 to 266 of human RUNX3. The AS251 antibody was immunoreactive with only RUNX3 protein, but not with RUNX1 and RUNX2. The AS251-antibody was available for Western blotting and immunohistochemistry using paraffin-embedded specimens. RESULTS: Western-blot analysis revealed that three (MKN-1, -7 and -45) of six human gastric carcinoma cell lines variably expressed RUNX3 protein, consistent with the expression pattern of RUNX3 mRNA reported previously by Li et al. (Cell 2002;109:113-24). Immunohistochemistry disclosed RUNX3 protein in most chief cells and a few gastrin-containing G cells in normal mucosa, but not in intestinal metaplasia and carcinoma cells. CONCLUSIONS: These data suggest that RUNX3 may play a physiologic role in chief cells and G cells in gastric mucosa, and that suppression of RUNX3 expression in intestinal metaplasia and carcinoma of human stomach may be implicated in gastric carcinogenesis.

Amino Acid Sequence↗
PubMed1990

Mucin histochemistry and lectin binding sites in intestinal metaplasia of the urinary bladder.

We report a case of intestinal metaplasia of the bladder urothelium associated with dysplastic foci and a transitional cell carcinoma. A mixture of sialomucins, O-acetylated sialomucins and sulphomucins was found in the goblet cells. Neuraminidase resistant binding of the lectin peanut agglutinin was demonstrated in the brush border of columnar cells in intestinal metaplasia and diffusely in columnar cells in dysplastic foci. The histochemical findings are compared with those described in normal, dysplastic and neoplastic colonic mucosa.

Aged↗
PubMed1990

The histological and immunohistochemical evidence of squamous metaplasia from the myoepithelial cells in the breast.

Squamous metaplasia in the breast is well documented. However, the putative cell of origin for the squamous epithelium is not clear. This paper describes a case of fibroadenoma of the breast with myoepithelial hyperplasia and squamous metaplasia. The histological finding of transition between myoepithelial cells and squamous cells and the immunohistochemical expressions of actin and S-100 in the metaplastic squamous cells support the myoepithelial origin of squamous epithelium in the breast.

Actins↗
PubMed1991

The L1 antigen and squamous metaplasia in the bladder.

The L1 antigen was investigated as a marker of squamous differentiation in urothelium using a monoclonal antibody Mac387, and the results were compared with the expression of high molecular weight cytokeratins. L1 antigen was consistently demonstrated in all instances of partial and complete squamous metaplasia and in squamous carcinomas. In contrast, pure transitional cell carcinomas (except one with minor focal staining), adenocarcinomas and normal and hyperplastic urothelium did not label. In a few squamous carcinomas in situ, the pattern of labelling obtained with Mac387 was different from that seen in invasive squamous carcinomas and metaplasias. Compared with high molecular weight cytokeratins, the expression of L1 was more intense in areas of squamous differentiation. L1 expression, as identified by antibody Mac387, may therefore serve as a useful marker of squamous differentiation in urothelial lesions.

Antibodies, Monoclonal↗
PubMed1993

Necrotizing squamous metaplasia in herpetic tracheitis following prolonged intubation: a lesion similar to necrotizing sialometaplasia.

In the last year we have encountered three cases of clinically inapparent herpes simplex virus (HSV) tracheitis in biopsies from patients undergoing tracheostomy following prolonged intubation. The diagnosis was based on finding characteristic inclusion-bodies on haematoxylin and eosin stained sections and was confirmed by immunohistochemical staining of infected cells with antibodies to HSV. A prominent mononuclear infiltrate, originally described in HSV oesophagitis, was recognized in two cases. Diffuse squamous metaplasia of both surface and glandular epithelium adjacent to necrotic ulcerated areas was evident in all three cases. Where extensive, the necrotizing squamous metaplasia of the glandular/ductal component was similar to necrotizing sialometaplasia of salivary glands, and likewise simulated squamous or mucoepidermoid carcinoma.

Adult↗
PubMed1995

Melanotic oncocytic metaplasia of the nasopharynx.

Two cases of melanotic oncocytic metaplasia occurring in the nasopharynx are reported. One presented with serous otitis media and the other with tinnitus. Nasoscopic examination revealed a small brown nodule obstructing the Eustachian tube in both cases. While oncocytic metaplasia of the nasopharynx is not too uncommon, melanin pigmentation of the nasal or nasopharyngeal mucosa is very rare. To our knowledge, their combination has not been described.

Aged↗
PubMed2005

Effect of suplatast tosilate on goblet cell metaplasia in patients with asthma.

BACKGROUND: Goblet cell metaplasia is a pathologic characteristic of asthma, associated with excess mucus secretion. Interleukin (IL)-4 and IL-13 plays an important role in mucus hypersecretion. Suplatast tosilate (suplatast), an antiallergic agent, is a Th2 cytokine inhibitor that suppresses the synthesis of IL-4, IL-5, IL-13, and eosinophilic airway inflammation. OBJECTIVE: We examined the effects of suplatast on mucus production in bronchial biopsy specimens taken from asthmatic subjects. METHODS: Oral suplatast 300 mg daily, or placebo was administered for 3 months in a double-blind, parallel-group study in 25 patients with asthma. Biopsy specimens were evaluated at before and after treatment for alcian blue/period acid-Schiff (AB/PAS), MUC5AC staining in bronchial epithelium and IL-4+, IL-13+ cells as well as inflammatory cells in lamina propria. RESULTS: There were significant decreases in the percentage of AB/PAS (P < 0.01) and MUC5AC (P < 0.01) stained area in the suplatast group. These changes were accompanied by significant decreases in IL-4+ and IL-13+ cells in suplatast-treated subjects. Additionally, we have observed that the number of infiltrating eosinophils and CD4+ T cells significantly decreased. CONCLUSIONS: These findings suggest that suplatast prevents goblet cell metaplasia through modulation of Th2 cytokine production and the recruitment of eosinophils and CD4+ T cells in the asthmatic airways.

Administration, Oral↗
PubMed1983

Induction of squamous metaplasia: requirement for cell multiplication, and competition with lobuloalveolar development in cultured mammary glands.

Mouse mammary glands were previously shown to undergo either of two courses of development and differentiation in whole organ culture. The combination of insulin, prolactin, aldosterone, and hydrocortisone induces a structural development of lobuloalveoli, followed by casein production. In the second course, the mixture of dibutyryl cyclic AMP, prostaglandins E1, E2 and B1, and papaverine brings about an extensive squamous metaplasia and excessive keratinization. In the present study, the foci of the metaplastic squamous cells appeared to originate from single or very few cells. A preferential stimulation of squamous cell multiplication was involved in the induction process. Twice the relative number of nuclei incorporated 3H-thymidine in the squamous metaplastic cells than in the surrounding cuboidal epithelium, according to autoradiography. The necessity for cell multiplication was indicated by the reversible and complete inhibitions of both the metaplastic squamous development and 3H-thymidine incorporation by 1 mM hydroxyurea in the culture medium. Simultaneous inductions of both courses of development and differentiation revealed a competitive and reciprocal relationship between the two pathways. The concurrent expressions of both courses were considerably less than those achieved when either pathway was induced alone. Only the combination of the three types of inducers of squamous metaplasia was able to compete effectively with the hormonal induction of lobuloalveolar development and differentiation. The findings suggest that individual metaplastic squamous foci may originate as clones of cells by processes that require cell multiplication, rather than through a direct non- replicative conversion of pre-existent cells of the cuboidal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

A histopathological study on the islets of Langerhans and ductal epithelial metaplasia in atrophic lobuli of pancreas.

In autopsy material isolated islets of Langerhans are frequently encountered in the fatty or the fibrous tissue replacing the pancreatic lobuli. The incidence of isolated islets of Langerhans was 27.0% in the file of a series of randomly selected 100 autopsy cases and increased with advancing age. Fifteen cases of these 27 showed multiple foci and the total number of foci counted 60. Fifty-two foci (86.7%) were found in the subcapsular area. Clusters of elastic fibers were found in 36 foci (60.0%). Small pancreatic ducts with goblet cell metaplasia were found in 29 foci (48.0%) in the surrounding tissue of the remaining islets of Langerhans. Squamous metaplasia was identified in only 1 focus (0.2%), and luminal dilatation of the duct was found in 4 foci (0.7%). Serial sections showed that the small duct ended without connection to acinar cells. "The isolated islets of Langerhans" should be the result of the atrophy of pancreatic lobuli subsequent to disappearance of acinar cells.

Adult↗
PubMed1991

Tubular adenoma of the gallbladder with squamoid spindle cell metaplasia. Report of three cases with immunohistochemical study.

Three cases of tubular adenoma of the gallbladder with squamoid spindle cell metaplasia are reported. Two of the three patients, who were middle-aged Japanese, had a solitary polyp in the gallbladder, and the other had three polyps. All the lesions were detected incidentally by ultrasonography. The polyps were pedunculated with a fine or frail stalk, and ranged from 0.5 to 3.9 cm in diameter. Histologically, they were tubular adenomas accompanied by scattered foci composed of a compact collection of short-spindle or oval cells with mild atypia. These cells did not retain intercellular bridges, and lacked intracellular keratinization. Immunohistochemically, the spindle cells stained positively for high-molecular-weight cytokeratin (EAB 903, a marker of squamous cell differentiation), whereas adenoma cells lining the tubules were negative for this antigen. Therefore, the spindle cell component is considered to represent squamoid metaplasia of adenoma cells.

Adenoma↗
PubMed1997

Carcinoma of the lung in Okinawa, Japan: with special reference to squamous cell carcinoma and squamous metaplasia.

In Okinawa, a subtropical island in southern Japan, squamous cell carcinoma (SCC), especially the well-differentiated form, is prevalent, while this form is relatively rare in both the mainland and other countries (e.g. United States of America). More patients with SCC from Okinawa, moreover, were positive for human papillomavirus (HPV) DNA by polymerase chain reaction (PCR) (79%), and harbored HPV types 6, 16 and 18, in combination. On the other hand, less than 30% of the mainland patients were positive for HPV DNA by PCR. Those patients who were positive all harbored only one HPV type. Furthermore, in Okinawa, there were a significant number of cases with adenosquamous carcinoma, and they too were positive for HPV DNA. The SCC and the adenocarcinoma cells adjacent to the SCC component in these cases were also positive for HPV DNA, and such adenocarcinoma cells were enlarged in size with relatively wide cytoplasm. The authors postulate that HPV infects adenocarcinoma cells and changes them to enlarged cells, followed by squamous metaplasia. In this report, HPV DNA was transfected to adenocarcinoma cells (cultured cell lines) and this showed that HPV causes squamous metaplasia. In addition, aberrant expression of p53 was demonstrated in a large number of the SCC cases in Okinawa. The enlarged adenocarcinoma cells adjacent to the SCC components in adenosquamous carcinomas also showed aberrant expression of p53. The recent advances in the studies of anti-oncogenes, p53, etc. and oncogenes are outlined. It is to be noted that the molecular mechanisms of carcinogenesis in the lung have been studied in general, classifying lung tumors into two groups, namely, small cell carcinoma (SCLC) and non-small cell carcinoma (NSCLC). However, because human lung cancer is represented by a wide variety of histologic types, molecular genetic studies according to a more detailed histological subclassification is needed.

Adult↗
PubMed1997

Mucinous adenocarcinoma arising in a giant urachal cyst associated with pseudomyxoma peritonei and stromal osseous metaplasia.

An unusual urachal lesion, which is a mucinous adenocarcinoma arising in a giant urachal cyst and is associated with pseudomyxoma peritonei and stromal osseous metaplasia of the cyst wall, was examined in a 45-year-old male. The cyst was encapsulated, measured 22 x 20 x 20 cm and weighed 3800 g. The unilocular cavity was filled with mucin. Most of the cystic cavity was lined with tall, simple or stratified columnar epithelium with a focus of papillary projection into the cavity. These findings suggest that this cystic lesion represents cystadenoma rather than a simple cyst. Foci of invasive moderately differentiated mucinous adenocarcinoma were detected in the area of macroscopic papillary fronds. Carcinoembryonic antigen and CA19-9 were immunohistochemically positive for tumor cells and their serum levels were also elevated. Stromal dystrophic calcification was extensively observed in the cyst wall with foci of osseous metaplasia. Mucinous implants, which histologically demonstrated adherent mucinous masses without epithelial components on the surface, were observed in the pelvic and abdominal cavity, indicating pseudomyxoma peritonei.

Adenocarcinoma, Mucinous↗
PubMed1997

Primary squamous metaplasia of the breast.

A case of primary or idiopathic squamous metaplasia of the breast occurring in a 45-year-old woman is presented. Immunohistochemical studies suggested that the metaplasia had arisen in ductular epithelium. No evidence of neoplasia was identified.

Biomarkers, Tumor↗
PubMed1998

Primary localized amyloid tumor of the breast with osseous metaplasia.

A case of primary localized amyloid tumor of the breast is described. It is an extremely rare condition and has not been seen in literature in Japan. A 76-year-old woman visited a hospital because of a painless, hard mass of the right breast. A relatively well demarcated, calcified mass was excised under clinical diagnosis of fibroadenoma. Histologically, massive eosinophilic amorphous material was deposited in breast stroma. It was stained red-orange by Congo red and displayed apple-green birefringence under polarized light. The staining persisted after incubation with KMnO4 and immunolabeling by immunoglobulin chi-light chain antiserum, consistent with the amyloid of AL (Achi) type. Osseous metaplasia with bone marrow cavity, foreign body type giant cells in response to amyloid, and scattered plasma cell infiltration were also recognized. Osseous metaplasia in the breast amyloid tumor has been reported in only one case before. To date, the patient has not developed any clinical or laboratory evidence of systemic amyloidosis or multiple myeloma.

Aged↗
PubMed2004

Chronology of the Barrett's metaplasia-dysplasia-carcinoma sequence.

The objective of this study was to assess the course over time of the Barrett's metaplasia-dysplasia-carcinoma sequence. The method used was a retrospective analysis of the medical records of a patient series with a median follow-up of 25 months. The study was undertaken in a university hospital foregut laboratory. The progress of seven patients was followed through the sequence of Barrett's esophagus, low-grade dysplasia and high-grade dysplasia to cancer. They all underwent subsequent esophagectomy and were found to have intramucosal adenocarcinoma. The main outcome measure was the time from the first diagnosis of intestinal metaplasia to the development of low-grade dysplasia, high-grade dysplasia and adenocarcinoma. Low-grade dysplasia developed in a median of 24 months, high-grade dysplasia after a median of 33 months and cancer after 36 months. All patients underwent esophagectomy with reconstruction and no patient has had a recurrence at a median follow-up of 25 months (range 10-204 months). Patients on Barrett's surveillance who develop early esophageal adenocarcinoma did so within approximately 3 years after the diagnosis of non-dysplastic Barrett's esophagus.

Adenocarcinoma↗
PubMed1985

Adenomatous metaplasia (nephrogenic adenoma) of urothelium. An analysis of 70 cases.

A retrospective analysis of 70 cases of adenomatous metaplasia seen in the St Peter's Hospitals over a 15-year period has been carried out. The lesions occurred at all ages (7-81 years) and in both sexes (51 males, 19 females) and were found throughout the urinary tract from pelvis to urethra. In the pelvis and ureter the finding was usually an incidental one in association with stones or chronic inflammation; ulceration was a frequent accompaniment. Most vesical and urethral lesions followed a surgical procedure months or years previously, the patients re-presenting with haematuria or irritative bladder symptoms. The endoscopic appearances varied but there was often a striking correlation between the location of the lesions and the site of previous surgery. The association of adenomatous metaplasia with ulceration and previous surgery leads us to suggest that it is merely an unusual response to wound healing and attempts to treat it by diathermy resection are, therefore, likely to meet with limited success. Cystoscopic follow-up of persistent lesions gives no reason to suppose they are pre-malignant.

Adenoma↗
PubMed2001

Effect of lifestyle, smoking, and diet on development of intestinal metaplasia in H. pylori-positive subjects.

OBJECTIVES: This study aimed to evaluate the influence of environmental and sociodemographic factors and the effect of smoking, alcohol, and dietary habits on the risk of gastric intestinal metaplasia (IM) in Helicobacter pylori-infected subjects. METHODS: The investigation was based on 2598 consecutive volunteer blood donors tested for the presence of antibodies against H. pylori from March 1995 to March 1997. Endoscopy with multiple biopsies was offered to all H. pylori-positive, symptomatic subjects. The presence or absence of IM was diagnosed by gastric biopsies. A serologically H. pylori-positive subject with gastric IM was defined as a case, whereas serologically H. pylori-positive subjects without IM were used as controls. All patients answered a detailed questionnaire collecting sociodemographic characteristics and smoking, alcohol drinking, and dietary habits. Odds ratios (ORs) and their 95% CIs were estimated by unconditional logistic regression, including terms for age and sex, to assess the association between the data collected and IM. RESULTS: Three hundred forty-four subjects with serological H. pylori infection and upper-GI symptoms underwent GI endoscopy, during which biopsies were taken for histological diagnosis. Histology revealed metaplasia in 74 subjects (21.5%). Incomplete IM was found in 37.8% of these cases. No significant associations were found between IM and anthropometric or sociodemographic factors. There was a significant association between age and IM (chi2 for trend, 6.67; p value, 0.009). Current smokers of over 20 cigarettes per day had a 4-fold risk of IM (OR, 4.75, 95% CI, 1.33-16.99). A 2-fold increased risk was found for high butter consumers (OR, 2.17; 95% CI, 1.14-4.11). No significant specific associations were found between the variables studied and complete or incomplete IM. CONCLUSIONS: This study found that smoking and high butter consumption may increase the risk of having gastric IM in H. pylori-positive subjects.

Adult↗
PubMed2001

Short segment Barrett's esophagus: relationship of age with extent of intestinal metaplasia.

OBJECTIVE: Short segment Barrett's esophagus (SSBE) is defined by the presence of intestinal metaplasia in biopsies obtained from mucosa with an appearance suggestive of Barrett's that extends <3 cm into the esophagus. It has been suggested that this lesion may represent a stage in an ongoing process of Barrett's esophagus progression. If so, then the prevalence of SSBE would be expected to decrease with advancing age, and patients followed over time should exhibit an increase in the extent of columnar-lined esophagus. The aim of this study was to determine whether SSBE length progresses or regresses over time by following a prospective cohort and by assessing the relationship between age and the length, as well as prevalence of SSBE. METHODS: The study included consecutive patients who were evaluated prospectively by an upper endoscopy and were found to have SSBE between October, 1983, and December, 1999, at the Southern Arizona VA Health Care System. All patients underwent a systematic biopsy protocol, and a designated pathologist who reviewed all specimens confirmed the diagnosis of Barrett's esophagus. Patients were subsequently interviewed for demographic information. In those patients who were enrolled into our surveillance program, SSBE length was remeasured and intestinal metaplasia reconfirmed on follow-up endoscopies. RESULTS: Of 343 patients with endoscopically proven Barrett's esophagus, 116 (33.8%) were found to have SSBE. Almost all were male (97.4%) and white (85.3%), with a mean age of 60.1+/-1.0 yr. The prevalence of SSBE increased with age and reached a plateau during the seventh decade of life. One-way analysis of variance showed that there was no significant difference in the mean length of SSBE among the various age groups (p = 0.84). This trend was maintained when only the white group was assessed. Follow-up endoscopies were performed in 57 patients, revealing a mean interval of 64 months to the latest endoscopy, with no significant difference in SSBE length between the first and last endoscopy (p = 0.16). CONCLUSIONS: The prevalence of SSBE increases with age until the seventh decade of life. Finding that SSBE length does not change across the various age groups and during a 64-month mean follow-up, suggests that SSBE does not progress over time.

Adult↗