Metaplasia

Coexpression of cytochrome P450 monooxygenases (CYPs) and reductase was found in human gastric mucosa with intestinal metaplasia. Immunohistochemistry showed reactivity to P450 reductase in metaplastic epithelial cells and in pyloric gland cells in glands showing intestinal metaplasia. These cells exhibit NADPH-diaphorase activity. Reverse transcription-PCR analysis and Western blotting showed that CYP1A1 and CYP1A2 were expressed in specimens with intestinal metaplasia. Tissue distribution of CYP1A1 coincided with that of P450 reductase. However, immunoreactivity to CYP1A2 protein was localized only in the pyloric gland cells near the intestinal metaplastic gland. Salmonella typhimurium mutagen assay definitively revealed that microsomes prepared from gastric mucosa with intestinal metaplasia, in particular in the pyloric gland, functionally activated benzo(a)pyrene and 2-amino-3-methylimidazo [4,5-f]quinoline. These results indicate that carcinogen activation by CYP enzymes expres...

The formation of epithelial cell barriers results from the defined spatiotemporal differentiation of stem cells into a specialized and polarized epithelium, a process termed mesenchymal–epithelial transition. The reverse process, epithelial–mesenchymal transition (EMT), is a metastable process that enables polarized epithelial cells to acquire a motile fibroblastoid phenotype. Physiological EMT also plays an essential role in promoting tissue healing, remodeling or repair in response to a variety of pathological insults. On the other hand, pathophysiological EMT is a critical step in mediating the acquisition of metastatic phenotypes by localized carcinomas. Although metastasis clearly is the most lethal aspect of cancer, our knowledge of the molecular events that govern its development, including those underlying EMT, remain relatively undefined. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that oversees and directs all aspects of cell development, differentia...

We induced vitamin A depletion to define early and late changes during the histogenesis of squamous metaplasia of hamster tracheal epithelium. An early change is the "minimal morphological change" (MMC), in which the mucociliary epithelium is separated from the basement membrane by a continuous layer of basal cells. Immunohistochemistry showed an exclusive localization of the keratins K5 and K14 in basal cells of normal and MMC epithelia. At the MMC stage no staining was observed above the basal layer with antibodies to K5, but upon progression of the lesion to a squamous focus all cells from basal to terminally differentiated were positive for K5 and K14. In contrast, when we used antibodies to the keratins K6 or K13 all cells were negative in the normal epithelium and in the MMC epithelium. Successive layers of suprabasal squamous cells found in squamous metaplasia failed to express normal epidermal differentiation marker keratins K1 and K10 but expressed the proliferati...

Gastric biopsies of the non neoplastic area of 46 patients with gastric cancer and 59 gastric biopsies of dyspeptic patients without gastric cancer were reviewed by one pathologist, without knowing from which group they were coming, to determine the histopathologic findings. The results of both groups were compared. Intestinal metaplasia was found to be significantly higher in gastric cancer patients than in patients without neoplasia (54,3 and 25,4% respectively) (p=0,001). Also in patients with cancer and intestinal metaplasia, this was of the complete type in about 80% of the cases. A number of items were assessed using logistic regression, we found that the presence of complete metaplasia, gastric atrophy and hypertrophy of the mucinogenous vacuole correlates with the presence of gastric cancer (p=0,0159 0,0080 y 0,0280 respectively). H.pylori presence was similar in both groups. The study was done between November 1997 and November 1998 at the Cayetano Heredia National Hospital...

In patients with adenoma, assessing premalignant changes in the surrounding mucosa is important for surveillance. This study evaluated atrophic and metaplastic progression in the background mucosa of adenoma or early gastric cancer (EGC) cases. Among 146 consecutive patients who underwent endoscopic resection for intestinal-type gastric neoplasia, the adenoma group included 56 patients with low-grade dysplasia and the ECG group included 90 patients with high-grade dysplasia or invasive carcinoma. For histology, 3 paired biopsies were obtained from the antrum, corpus lesser curvature (CLC), and corpus greater curvature (CGC). Serological atrophy was determined based on pepsinogen A (PGA), progastricsin (PGC), gastrin-17, and total ghrelin levels. Topographic progression of atrophy and/or metaplasia was staged using the operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia assessment (OLGIM) systems. Rates of moderate-to-marked histological ...

Intestinal-type gastric cancer is often preceded by intestinal metaplasia in humans. The genetic events responsible for the transdifferentiation that occurs in intestinal metaplasia are not well understood. Cdx2, a transcription factor whose expression is normally limited to the ...

After breast augmentation, additional operations are often needed for revision or explantation. Although the surgeon may elect to leave the capsule in situ during these procedures, excised capsule tissue may be examined histopathologically for cancer cells. The authors assessed pathologic findings from breast implant capsules submitted for histopathologic examination and evaluated whether it is oncologically safe to leave capsule tissue in situ. The authors searched PALGA, the nationwide histopathology and cytopathology data network and registry in the Netherlands, for primary capsulectomy specimens excised between 2003 and 2012. The authors applied a sensitive search strategy with low specificity that included female and breast as the sex and anatomic location keywords, and wildcards were used to detect different spellings. Cases were excluded if previous examinations showed compatibility with a history of breast cancer, prophylactic mastectomy, or prophylactic oophorectomy. The pa...

Background Gastric cancer (GC) is one of the most common cancers worldwide and shows remarkable geographical variation even within countries such as China. Iinqu County in Shandong Province of northeast China has a GC rate that is 15 times higher than that of Cangshan County in ...

After breast augmentation, additional operations are often needed for revision or explantation. Although the surgeon may elect to leave the capsule in situ during these procedures, excised capsule tissue may be examined histopathologically for cancer cells. The authors assessed pathologic findings from breast implant capsules submitted for histopathologic examination and evaluated whether it is oncologically safe to leave capsule tissue in situ. The authors searched PALGA, the nationwide histopathology and cytopathology data network and registry in the Netherlands, for primary capsulectomy specimens excised between 2003 and 2012. The authors applied a sensitive search strategy with low specificity that included female and breast as the sex and anatomic location keywords, and wildcards were used to detect different spellings. Cases were excluded if previous examinations showed compatibility with a history of breast cancer, prophylactic mastectomy, or prophylactic oophorectomy. The pa...

Reflectance spectroscopy is an emerging technology which provides rapid and safe evaluation of tissue for dysplasia and ischemia. The probe-based devices can be passed through most endoscopes. Current applications include detection of dysplasia in Barrett's esophagus, colitis, and colon polyps.

Children chronically exposed to high levels of ozone (O3), the principal oxidant pollutant in photochemical smog, are more vulnerable to respiratory illness and infections. The specific factors underlying this differential susceptibility are unknown but may be related to air pollutant-induced nasal alterations during postnatal development that impair the normal physiological functions (e.g., filtration and mucociliary clearance) serving to protect the more distal airways from inhaled xenobiotics. In adult animal models, chronic ozone exposure is associated with adaptations leading to a decrease in airway injury. The purpose of our study was to determine whether cyclic ozone exposure induces persistent morphological and biochemical effects on the developing nasal airways of infant monkeys early in life. Infant (180-day-old) rhesus macaques were exposed to 5 consecutive days of O3 [0.5 parts per million (ppm), 8 h/day; “1-cycle”] or filtered air (FA) or 11 biweekly cycles of O3 (FA da...

Three hundred and fifty biopsies from patients undergoing upper gastrointestinal endoscopy were studied for histopathological changes, H. pylori infection and argyrophilic nucleolar organizer region (AgNOR) counts. Histopathological examination revealed normal gastric mucosa in 10 (2.85%), gastritis in 254 (72.56%), intestinal metaplasia in 12 (4.0%), dysplasia in 13 (3.7%) and adenocarcinoma in 61 (17.4%). The mean (SD) AgNOR count was 1.66 (0.20) in normal, 2.43 (0.64) in gastritis, 3.09 (0.52) in intestinal metaplasia, 4.17 (0.31) in dysplasia, and 6.57 (0.98) in carcinoma. A statistically significant difference was observed between the AgNOR count of normal gastric mucosa and gastritis (p<0.001), gastritis and dysplasia (p<0.001), and dysplasia and adenocarcinoma (p<0.001). A statistically significant increase in mean AgNOR count was found with increase in H. pylori density in gastric biopsies (p<0.001) with gastritis. No significant difference was observed between mean AgNOR count of intestinal and diffuse type carcinomas. The AgNOR count in gastric biopsies with adenocarcinoma and H. pylori infection was 7.03 (0.85) as compared to 6.89 (0.73) in gastric biopsies with evidence of adenocarcinoma but without H. pylori infection. The difference was not statistically significant. The findings support the role of H. pylori as a promoting agent in gastric carcinogenesis by stimulating gastric epithelial cell proliferation at the stage of chronic inflammation, thereby making the cells more susceptible to endogenous or exogenous carcinogenic agents.

We studied 111 gastrectomies from patients harboring primary adenocarcinomas (30 intestinal and 30 diffuse type) and 51 gastric lymphomas. For comparative purposes, we analized 86 stomachs from patients who died of diseases other than gastric malignancies. Histopathological ...

Experiments were designed to define the ability of retinoic acid to block the estrogen-induced metaplasia in the mouse anterior prostate gland (coagulating gland), and to elucidate some of the biochemical correlates of the actions and interactions of these two compounds. In castrated mice, the estrogen-induced metaplasia of epithelial cells consisted of multi-layered, nonpolarized cells, which accumulated to fill the lumen of the acini. Retinoic acid had no discernable effect on epithelial morphology of castrates, but significantly reduced the estrogen-induced metaplasia. Likewise, the estrogen-induced increases in the prostatic wet weight, ratio of ribonucleic to deoxy ribonucleic acids (RNA/DNA) and glycosyltransferases, as well as the decreases in 21,000 and 28,000 Mr soluble proteins were prevented by retinoic acid; the retinoid had no effect on these various parameters when administered alone to castrates. In contrast, the cyclic 3',5'-adenosine monophosphate (cAMP)-dependent phosphorylations at 16,000, 18,000, and 25,000 Mr and the activities of the type II cAMP-dependent kinase were uniformly reduced by both estradiol and retinoic acid. Tests of the action of the anti-estrogen LY-156758 on estrogen and retinoid effects showed that for those parameters on which retinoic acid was anti-estrogenic, LY-156758 was also anti-estrogenic. However, the qualitatively similar effects of retinoic acid and estradiol, which were confined to selected aspects of protein phosphorylation, were not antagonized by LY-156758. It is concluded that in the mouse anterior prostate, retinoic acid has both anti-estrogenic and estrogenic actions, and the latter may occur independently of the estrogen receptor.

Intestinal metaplasia (IM) is a gastric cancer precursor lesion (GCPL) and an extremely high risk factor for progression to gastric cancer (GC). Clinical guidelines recommend that patients with extensive IM undergo a gastroscopy every 3 years. However, protein biomarkers that indicate a transition from IM to GC are lacking. Our group recently identified an interferon-alpha (IFNα)-responsive gene, Schlafen 4 (Slfn4), in immune cells that correlates with metaplastic changes in Helicobacter-infected mice. We therefore tested the hypothesis that a human homolog of Slfn4, namely, Schlafen 5 (SLFN5), correlates with progression of GCPL to GC. Jurkat T-lymphoid and HL-60 myeloid cell lines were treated with IFNα, and SLFN5 mRNA was quantified by quantitative PCR. SLFN5 protein expression in the inflamed gastric mucosa was co-localized to specific immune cell types by immunohistochemistry using CD20, CD2, and MAC2 antibodies. SLFN5 expression was also determined by immunohistochemistry in f...

To identify the main determinants of cellular atypia detection in the cervical screening program in the state of Rio de Janeiro, Brazil, using data from the Cervical Cancer Information System SISCOLO. A random sample of 65 535 Pap smears performed in 2007 was obtained from SISCOLO. This sample was used to produce a logistic regression model to identify variables that impact the process of detecting cellular atypia. A ROC curve was used to define the most suitable cutoff point to classify the presence or absence of atypia. A sensitivity analysis was performed to assess the impact on the model of factors related to the organization of the service model. The variables of impact were "reference…

Upper gastrointestinal endoscopy was performed on 14 of our 18 long-term (more than 2 years) gastric tube esophagus survivors, with special attention paid to cervical gastric metaplasia. Barrett's esophagus was found in 10 patients. In eight cases, this could also be histologically verified. Three patients had esophagitis, but no verified gastric metaplasia. Isotope reflux studies were performed on six patients, all having both endoscopically and histologically shown pathology in the cervical esophagus. Reflux was provoked by putting patients in different positions. Only one patient showed gastrotubal reflux, and only in the prone Trendelenburg position. We conclude that Barrett's esophagus is a common complication of gastric tube patients, and is probably due to acid secreted by the tube itself. Life-long endoscopic follow-up of these patients is warranted.