Pathological case of the month. Intracranial plasma cell granuloma.
Explore the source record for details and available documents.
Brain Diseases↗
Biomedical subjects
K Washington
Publications and source records attributed to K Washington.
Hepatic cryoablation-induced acute lung injury: histopathologic findings.
We have previously shown that hepatic cryoablation (cryo), but not partial hepatectomy, induces a systemic inflammatory response, with distant organ injury and overproduction of NF-kappaB-dependent cytokines. Serum tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) levels are markedly increased 1 h and beyond after cryo compared with partial hepatectomy where no elevation occurs. NF-kappaB activation (by electrophoretic mobility shift assay) is strikingly increased in the noncryo liver (but not in the lung) at 30 min and in both the liver and lung tissue 1 h after cryo, returning to the baseline by 2 h and beyond. The current study investigated the histopathologic changes associated with cryoablation-induced acute lung injury. Animals underwent 35% hepatic resection or a similar volume hepatic cryo and were sacrificed at 1, 2, 6, and 24 h. Pulmonary histologic features were assessed using hematoxylin and eosin and immunoperoxidase staining with a macrophage-specific antibody (anti-lysozyme, 1:200 dilution, Dako, Carpinteria, CA). The following features were graded semiquantitatively (0-3): perivascular lymphoid cuffs, airspace edema and hemorrhage, margination of neutrophils within pulmonary vasculature, and the presence of macrophages with foamy cytoplasm in the pulmonary interstitium. Hepatic resection (n = 21) resulted in slight perivascular edema at 1, 2, 6, and 24 h post-resection, but there were no other significant changes. Pulmonary findings after hepatic cryo (n = 22) included prominent perivascular lymphoid cuffs 1 and 2 h following hepatic injury that were not present at any other time point (P 0.01). Marginating PMNs and foamy macrophages were more common after cryo at all time points (P<0.05, cryo vs resection). Severe lung injury, as evidenced by airspace edema and parenchymal hemorrhage, was present in four of six (67%) animals at 24 h (P 0.03). In follow-up studies immediate resection (n = 15) of the cryo-treated liver prior to thawing prevented the pulmonary changes. The findings of pulmonary perivascular interstitial macrophages 2 h following hepatic cryo suggests that hepatic cytokine production may induce downstream recruitment of pulmonary macrophages, which may contribute to subsequent severe lung injury. This study suggests that a soluble mediator from direct liver injury leads to neutrophilic lung inflammation and this is associated with the thawing phase of cryoablation.
Animals↗
Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation.
Morphologic assessment of dysplasia in Barrett esophagus, despite limitations, remains the basis of treatment. We rigorously tested modified 1988 criteria, assessing intraobserver and interobserver reproducibility. Participants submitted slides of Barrett mucosa negative (BE) and indefinite (IND) for dysplasia, with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), and with carcinoma. Two hundred fifty slides were divided into 2 groups. The first 125 slides were reviewed, without knowledge of the prior diagnoses, on 2 occasions by 12 gastrointestinal pathologists without prior discussion of criteria. Results were analyzed by kappa statistics, which correct for agreement by chance. A consensus meeting was then held, establishing, by group review of the index 125 slides, the criteria outlined herein. The second 125-slide set was then reviewed twice by each of the same 12 pathologists, and follow-up kappa statistics were calculated. When statistical analysis was performed using 2 broad diagnostic categories (BE, IND, and LG v HG and carcinoma), intraobserver agreement was near perfect both before and after the consensus meeting (mean kappa = 0.82 and 0.80). Interobserver agreement was substantial (kappa = 0.66) and improved after the consensus meeting (kappa = 0.70; P =.02). When statistical analysis was performed using 4 clinically relevant separations (BE; IND and LGD; HGD; carcinoma), mean intraobserver kappa improved from 0.64 to 0.68 (both substantial) after the consensus meeting, and mean interobserver kappa improved from 0.43 to 0.46 (both moderate agreement). When statistical analysis was performed using 4 diagnostic categories that required distinction between LGD and IND (BE; IND; LGD; HGD and carcinoma), the pre-consensus meeting mean intraobserver kappa was 0.60 (substantial agreement), improving to 0.65 after the meeting (P <.05). Interobserver agreement was poorer, with premeeting and postmeeting mean values unchanged (kappa = 0.43 at both times). Interobserver agreement was substantial for HGD/carcinoma (kappa = 0.65), moderate to substantial for BE (kappa = 0.58), fair for LGD (kappa = 0.32), and slight for IND (kappa = 0.15). The intraobserver reproducibility for the diagnosis of dysplasia in BE was substantial. Interobserver reproducibility was substantial at the ends of the spectrum (BE and HG/carcinoma) but slight for IND. Both intraobserver and interobserver variation improved overall after the application of a modified grading system developed at a consensus conference but not in separation of BE, IND, and LGD. The criteria used by the group are presented. HUM PATHOL 32:368-978.
Algorithms↗
Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study.
The objective of endoscopic surveillance in Barrett esophagus (BE) is to assess the risk of subsequent development of invasive carcinoma. Criteria for morphologic evaluation of dysplasia, the presumed precursor lesion, have been established, although there are surprisingly few data in the literature correlating biopsy diagnosis of dysplasia with outcome. We collected follow-up information on 138 patients with BE whose initial endoscopic biopsy specimens had been selected for submission in an interobserver variability study performed by 12 pathologists with special interest in gastrointestinal pathology and reviewed blindly twice each by all the participants. Cases were scored as BE with no dysplasia, atypia indefinite for dysplasia (IND), low-grade dysplasia (LGD), high-grade dysplasia (HGD), intramucosal carcinoma, and frankly invasive carcinoma, thus generating 24 scores on each biopsy specimen. Clinical follow-up was obtained and correlated with both the submitting diagnoses and majority diagnoses. Kaplan-Meier statistics were used to compare both the submitting and majority diagnoses with outcome using detection or documentation of invasive carcinoma as the endpoint. Using the submitting diagnoses, no invasive carcinomas were detected in 44 cases diagnosed as BE (median follow-up, 38.5 months). Carcinomas were detected in 4 of 22 (18%) cases submitted as IND (median progression-free survival of 62 months), in 4 of 25 (15%) cases of LGD (median progression-free survival of 60 months), in 20 of 33 cases of HGD (median progression-free survival, 8 months), and all 13 (100%) cases submitted as adenocarcinoma. Grade on initial biopsy correlated significantly with progression to invasive carcinoma (log-rank P =.0001). Majority diagnosis was achieved in 99 of the cases. Using the majority diagnoses, no invasive carcinomas were found in 50 cases of BE (median follow-up, 48 months), and carcinomas were detected in 1 of 7 (14%) IND cases (80% progression-free survival at 2 months), 3 of 15 (20%) LGD (median progression-free survival, 60 months), 9 of 15 (60%) HGD (median progression-free survival, 7 months), and all 12 (100%) carcinoma. Initial grading again correlated significantly with progression to invasive carcinoma (log-rank P =.0001). However, there were 39 cases without a majority diagnosis. Among these, no carcinomas developed in 8 cases with an average score between BE and IND. Carcinomas were detected in 9 of 21 (43%) cases with an average score between IND and LGD, and 7 of 10 (70%) cases with an average score between LGD and HGD. There were ulcers in 8 of 39 cases (20%) of the "no-majority" group and in 13 of 99 (13%) of the majority cases. Of 21 total ulcerated cases, cancer was demonstrated in 15 (71%) of these on follow-up. These data support combining the IND and LGD categories for surveillance purposes. Cases without dysplasia may be followed up conservatively. The data obtained from submitted diagnoses as opposed to those from blind review suggest that knowledge of the clinical findings aids in diagnosis. The data also support the assertion that HGD is strongly associated with invasive carcinoma. Rebiopsy of ulcerated areas should be considered because they may harbor malignancy. Histologic grading of dysplasia using established criteria is a powerful prognosticator in BE. HUM PATHOL 32:379-388.
Adolescent↗
Contemporary trends and practice strategies in pediatric occupational and physical therapy.
This paper identifies and reflects on recent trends in pediatric occupational therapy and physical therapy practice. These trends were initially identified by the student authors for a Maternal and Child Health (MCH) leadership seminar, which was conducted as part of the postprofessional graduate program in physical therapy at the University of Washington. Trends were then reviewed and discussed among the student and faculty authors. Consensus was reached on the most important trends, which were subsequently summarized in this paper. The first part of the paper reviews the impact of these trends on current and future clinical practices in health, educational, and community-based settings. The second part of the paper offers proposed directions to meet the challenges presented by the trends in four key areas; (1) research, (2) professional education, (3) enhancing family-centered care, and (4) advocacy.
Female↗
Treatment of Ménétrier's disease with a monoclonal antibody against the epidermal growth factor receptor.
Explore the source record for details and available documents.
Anaphylaxis↗
Prevalence and prognostic significance of neuroendocrine cells in esophageal adenocarcinoma.
Neuroendocrine differentiation is common in adenocarcinomas of the stomach and colon and may be associated with a slightly better prognosis in gastric adenocarcinoma. We studied neuroendocrine differentiation in esophageal adenocarcinomas and associated Barrett's esophagus (BE) to determine association with patient outcome. Fifty-eight cases of esophageal adenocarcinoma (15 biopsies, 43 resections) from 52 patients were stained with a monoclonal antibody to chromogranin (CG). Medical records were reviewed for tumor stage, response to therapy, and patient survival. Thirty-two patients received radiation and chemotherapy, and four received radiation. Twelve of 58 (20.7%) esophageal adenocarcinomas contained scattered CG-positive cells. Tumors with CG-positive cells were moderately to poorly differentiated, and many consisted of large cribriform glands, similar to intestinal-type adenocarcinomas. One case of small cell carcinoma of the esophagus was weakly CG positive; another was negative. Neuroendocrine differentiation was retained in lymph node metastases in two cases but lost in three other cases. In 10 CG-negative primary tumors, lymph node metastases were also negative. For five of six patients with paired biopsy/resection specimens, no CG-positive cells were seen in either specimen; one patient had CG-positive cells only in the resection. There was no difference in tumor stage at surgery or survival time between CG-positive and CG-negative tumors. BE was present in 34 cases and contained CG-positive cells in 21 of 34 (61.8%). Low-grade dysplasia contained CG-positive cells in 11 of 14 cases (78.6%) and high-grade dysplasia in 3 of 6 cases. Fourteen of 21 (66.7%) adenocarcinomas associated with CG-positive BE were negative for CG. In summary, neuroendocrine differentiation is common in BE and is retained in low- and high-grade dysplasia but is usually lost in esophageal adenocarcinoma. The presence of scattered neuroendocrine cells does not affect patient outcome.
Adenocarcinoma↗
Hepatic stellate cell activation in nonalcoholic steatohepatitis and fatty liver.
Factors associated with the development of fibrosis in nonalcoholic steatohepatitis (NASH) are largely unknown, although an association with increased hepatic iron has been suggested. Hepatic stellate cells are the principal collagen-producing cells in many liver diseases and when activated express alpha-smooth muscle actin (alpha-SMA). Hepatic stellate cell activation and association with fibrosis, necroinflammatory activity, steatosis, and stainable iron in 60 cases of NASH and 16 cases of steatosis were evaluated. All 76 patients were obese or had other risk factors for NASH. All biopsy specimens were stained for alpha-smooth muscle actin to evaluate the pattern of hepatic stellate cell activation and were evaluated for inflammatory activity (0 to 3), fibrosis (0 to 4), and stainable iron stores (0 to 4). The zonal location of activated stellate cells was recorded, and the degree of activation was graded as high-grade or low-grade based on the percentage of lobular alpha-SMA+ cells. Activated stellate cells were identified in the hepatic lobule in 74 of 76 biopsy specimens and graded as low-grade in 26 and high-grade in 48. Zone 3 was involved in 72 of 74 positive cases, and in 33 cases, the activated stellate cells were preferentially located in zone 3. The degree of stellate cell activation correlated with fibrosis but not with inflammatory activity, severity of steatosis, or stainable iron. In most cases, the degree of stellate cell activation paralleled the degree of hepatic fibrosis, but in 25 cases, the degree of hepatic stellate cell activation was greater than expected, raising the question of whether such patients are at risk for disease progression.
Actins↗
Targeted disruption of the Kvlqt1 gene causes deafness and gastric hyperplasia in mice.
The KvLQT1 gene encodes a voltage-gated potassium channel. Mutations in KvLQT1 underlie the dominantly transmitted Ward-Romano long QT syndrome, which causes cardiac arrhythmia, and the recessively transmitted Jervell and Lange-Nielsen syndrome, which causes both cardiac arrhythmia and congenital deafness. KvLQT1 is also disrupted by balanced germline chromosomal rearrangements in patients with Beckwith-Wiedemann syndrome (BWS), which causes prenatal overgrowth and cancer. Because of the diverse human disorders and organ systems affected by this gene, we developed an animal model by inactivating the murine Kvlqt1. No electrocardiographic abnormalities were observed. However, homozygous mice exhibited complete deafness, as well as circular movement and repetitive falling, suggesting imbalance. Histochemical study revealed severe anatomic disruption of the cochlear and vestibular end organs, suggesting that Kvlqt1 is essential for normal development of the inner ear. Surprisingly, homozygous mice also displayed threefold enlargement by weight of the stomach resulting from mucous neck cell hyperplasia. Finally, there were no features of BWS, suggesting that Kvlqt1 is not responsible for BWS.
Animals↗
Cholestatic jaundice with skin desquamation in a 12-year-old girl.
Explore the source record for details and available documents.
Atropine↗
Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer.
Esophageal cancer is a major cause of morbidity and mortality worldwide. Although patients often present with apparently resectable disease, systemic spread frequently occurs before the development of symptoms and detection of tumor. The use of combined chemoradiation therapy, particularly before resection, appears to prolong survival and increase cure rates in certain histologic subtypes. Four randomized phase III trials compared preoperative chemoradiotherapy plus surgery with surgery alone. In trials including only patients with squamous histology, no improvement in survival was observed with preoperative chemoradiation therapy; however, in a trial including only patients with adenocarcinoma histology, improved median and overall survival were observed. Paclitaxel has been evaluated as a single agent in a phase II trial in previously untreated patients with locally advanced unresectable or metastatic esophageal cancer; the overall response rate was 32% and median survival was 13.2 months. Paclitaxel-based combinations also have been evaluated in esophageal cancer; particularly encouraging preliminary results have been achieved with paclitaxel/cisplatin/5-fluorouracil. Because paclitaxel is a potent radiosensitizer, it also has been evaluated in combination with radiation therapy for esophageal and other thoracic cancers, alone and in combination with other chemotherapeutic agents. Preliminary results suggest that neoadjuvant therapy with paclitaxel-based combinations (including 5-fluorouracil and cisplatin) and radiation is highly active, with variable toxicity. A goal of future trials is to assess paclitaxel-based combined modality therapy in combination with other new chemotherapeutic agents.
Antineoplastic Agents, Phytogenic↗
Acute lung injury after hepatic cryoablation: correlation with NF-kappa B activation and cytokine production.
BACKGROUND: Previous clinical reports have documented multisystem organ injury after hepatic cryoablation. We hypothesized that hepatic cryosurgery, but not partial hepatectomy, induces a systemic inflammatory response characterized by distant organ injury and overproduction of nuclear factor kappa B (NF-kappa B)-dependent, proinflammatory cytokines. METHODS: In this study, rats underwent either cryoablation of 35% of liver parenchyma or a similar resection of left hepatic tissue. Serum tumor necrosis factor-alpha and macrophage inflammatory protein-2 levels and NF-kappa B activation were assessed by electrophoretic mobility shift assay at 30 minutes 1, 2, 6, and 24 hours after either procedure. RESULTS: Cryoablation of 35% of liver (n = 22 rats) resulted in lung injury and a 45% mortality rate within 24 hours of surgery, whereas 7% treated with 35% hepatectomy (n = 15 rats) died during the 24 hours after surgery (P < .05, cryoablation vs hepatectomy). Serum tumor necrosis factor-alpha and macrophage inflammatory protein-2 levels were markedly increased in rats (n = 10 rats) 1 hour after hepatic cryoablation compared with rats that underwent partial hepatectomy (P < .005). We evaluated NF-kappa B activation by electrophoretic mobility shift assay in nuclear extracts of liver and lung after cryosurgery and found that NF-kappa B activation was strikingly increased in the liver but not the lung at 30 minutes and in both organs 1 hour after cryosurgery, and returned to baseline in both organs by 2 hours. In rats undergoing 35% hepatectomy, no increase in NF-kappa B activation was detected in nuclear extracts of either liver or lung at any time point. CONCLUSIONS: These data show that hepatic cryosurgery results in systemic inflammation with activation of NF-kappa B and increased production of NF-kappa B-dependent cytokines. Our data suggest that lung injury and death in this animal model is mediated by an exaggerated inflammatory response to cryosurgery.
Acute Disease↗
Alterations in colonic mucosal vessels in patients with cirrhosis and noncirrhotic portal hypertension.
Changes in intestinal mucosal microvasculature as a cause of lower gastrointestinal hemorrhage in patients with portal hypertension have been well documented clinically, but the analogous histomorphological changes have not been well characterized. The goal of this study was to evaluate qualitative and quantitative changes in colonic mucosal vessels in patients with cirrhosis or clinically evident portal hypertension and to correlate these changes with endoscopic and clinical findings. Colon biopsy or resection specimen slides from 46 patients with biopsy-proven cirrhosis (44 patients) or noncirrhotic portal hypertension (two patients) were reviewed. Immunoperoxidase stain for CD34 antigen was used to facilitate visualization of mucosal vessels, and vessel diameter was measured with a micrometer. Patients with inflammatory bowel disease were excluded. Twenty-four normal colon biopsy specimens served as controls. Mucosal vessels were divided into superficial, intermediate, and deep layers. As a group, the cirrhotic patients had a significantly higher mean diameter of vessels in all three layers. Qualitatively, increased numbers of small vessels and prominent branching were noted, especially in the superficial and intermediate layers. Tortuous, thick-walled vessels, suggesting arterialization of venules, were present in some cases. Eleven patients had endoscopic findings suggestive of vascular abnormalities, including erythematous mucosal patches, red macules, and telangiectasias. Eighteen had esophageal varices, and five had portal gastropathy. Nineteen patients had gastrointestinal (GI) bleeding, localized to the lower GI tract in 11. These qualitative and quantitative findings suggest that colonic mucosal vascular lesions are common in portal hypertension and may represent a potential source of clinically significant lower GI hemorrhage in these patients.
Adult↗
Can experimental models of rodent implantation glioma be improved? A study of pure and mixed glioma cell line tumours.
To evaluate the hypothesis that co-implantation of different rodent glioma cell lines might result in experimental brain tumours that more closely resemble human gliomas the neuropathology and immunocytochemical features of implantation gliomas derived from single cell lines (C6, A15A5, F98), two cell lines admixed 50:50 prior to implantation (C6 + F98 and C6 + A15A5) and three cell lines equally admixed (C6 + A15A5 + F98) was studied in the adult Wistar rat. Tumours grew consistently following implantation of the single and the two admixed cell lines, however tumour growth following triple mix implantation was considerably and consistently impaired. The tumours derived from admixed cell lines showed regional heterogeneity with areas characteristic of both the primary cell lines. Foci of lymphocytic infiltrates, tumoural necrosis, often with pseudopallisading, and peritumoural edema were consistent features of all tumours. Limited parenchymal and more extensive perivascular tumoural invasion was seen predominantly in tumours containing the C6 cell line. There were no significant differences in GFAP, vimentin and HSP70 staining between the mixed tumours, although the pure F98 and A15A5 tumours were, unlike the pure C6 gliomas, S-100 negative. Using PCNA expression as a measure of the tumour proliferation all except the tumours derived from the three cell lines mix, which had a staining index of 7-10%, had focal staining indices in viable tumour of between 40-80%. There was focal positive staining in both perilesional brain and in regions of all tumours for the macrophage markers ED-1 and ED-2. None of the three cell lines stained in vitro for either ED1 and ED2 but all were constitutively positive in vitro for OX-6, a proposed marker for antigen presenting cells. The macrophage and lymphocytic response suggest a vigorous but largely ineffective immunological response had been mounted against all tumours. The consistent failure of the triple mix tumours to grow is unexplained. This work has shown the feasibility of producing 'mixed' cell line experimental gliomas by combining two cell lines at the time of innoculation. However, the relative failure to produce (i) mixed tumours that have properties not inherent to either parent cell line and (ii) implantation glioma with three cell lines suggest there are limits to this approach. Admixture of cell lines at the time of implantation therefore does not make experimental glioma models that more closely resemble natural gliomas, and also has some particular disadvantages. This experimental approach is therefore not recommended for use in the study of tumour biology and in evaluating the effectiveness of novel therapies.
Animals↗
Functional studies on the anti-pathoangiogenic properties of CM101.
Group B streptococcus (GBS) isolated from human neonates diagnosed with sepsis and respiratory distress produces a polysaccharide exotoxin (CM101) which has been previously described as GBS toxin. CM101 infused i.v. into tumor-bearing mice causes rapid tumor neovascularitis, infiltration of inflammatory cells, inhibition of tumor growth and tumor apoptosis. CM101 has successfully completed phase I studies in refractory cancer patients with very encouraging results. We have now demonstrated a mechanism of action for CM101. Using a normal mouse tumor model, we have examined tumor and normal tissues which were harvested at 0, 5, 15, 30 and 60min post-infusion of either CM101 or dextran. We present evidence that CM101 is rapidly (within the first 5min) bound to the tumor neovasculature. Complement is activated by the alternative pathway (C3) and leukocytes start to infiltrate the tumor within the first 5min. Through RT-PCR and immunohistochemical techniques, we demonstrate that proinflammatory cytokines, interleukin-6 and tumor necrosis factor (TNF)-alpha, are up-regulated in infiltrating leukocytes and TNF receptor 2 is up- regulated in the targeted tumor neovasculature. Combined, these events constitute possible explanations for the observed pathophysiology of tumor ablation.
Journal Article↗
The Bayley Scales of Infant Development-II and children with developmental delays: a clinical perspective.
Explore the source record for details and available documents.
Developmental Disabilities↗
Liver regeneration is transiently impaired in urokinase-deficient mice.
To test the hypothesis that urokinase-type plasminogen activator (uPA) plays an important role in liver regeneration in vivo, partial hepatectomy was performed on wild-type and uPA-deficient (uPA-/-) mice. Mice were studied at 24, 44, and 96 h and at 8 days and 4 wk post-partial hepatectomy for evidence of regeneration, as measured by mitotic indexes and [3H]thymidine incorporation. In wild-type mice, thymidine incorporation peaked at 44 h and this index was reduced by 47% in uPA-/- mice (P = 0.02). By 8 days, however, liver mass was comparable in both groups. Histological analysis revealed the presence of focal areas of fibrin deposition and cellular loss by 24 h that were more severe and prevalent in uPA-/- mice than in wild-type mice (62 and 23%, respectively; chi2 = 3.939, P = 0.047). In contrast, regeneration was not impaired in uPA receptor (uPAR)-deficient mice at 24 and 44 h. Taken together, these data indicate that uPA, independent of its interaction with the uPAR, plays an important role in liver regeneration in vivo.
Animals↗
Expression of beta-catenin, alpha-catenin, and E-cadherin in Barrett's esophagus and esophageal adenocarcinomas.
Loss of expression and function of the E-cadherin/catenin membrane complex can result in loss of cell adhesion and contribute to invasive or metastatic potential in carcinomas. The aim of this study was to examine the expression of alpha- and beta-catenin and E-cadherin in Barrett's esophagus with and without dysplasia and in esophageal adenocarcinomas and to identify any relationship with tumor growth pattern and clinical outcome. Immunoperoxidase staining for alpha- and beta-catenin and E-cadherin was performed on specimens of Barrett's esophagus with and without dysplasia and on 54 esophageal adenocarcinoma specimens. Membranous staining for all of the components was seen in normal gastric and esophageal mucosa. Abnormal expression of beta-catenin, alpha-catenin, and E-cadherin was significantly associated with higher degrees of dysplasia in Barrett's esophagus. Fourteen of 16 cases of high grade dysplasia and 7 of 7 cases of intramucosal carcinoma showed abnormal expression of beta-catenin, compared with 3 of 6 cases indefinite for dysplasia and 11 of 17 cases with low grade dysplasia (P = 0.022). Similar results were seen for expression of alpha-catenin (P < .01) and E-cadherin (P = .049). In esophageal adenocarcinomas, preserved expression of these proteins occurred more frequently in well-differentiated tumors; abnormal expression was more common in diffusely infiltrative poorly differentiated tumors that did not form glands. Focal nuclear staining for beta-catenin was present in two high-grade dysplasias, two intramucosal carcinomas, and five adenocarcinomas. No survival advantage was demonstrated for patients whose tumors retained expression of these cell adhesion components. In conclusion, abnormal expression of the E-cadherin/catenin membrane complex is common in esophageal adenocarcinoma and occurs early in the dysplasia/carcinoma sequence in Barrett's esophagus, indicating that disturbances in this cell adhesion complex might be important in tumorigenesis and tumor progression in this disorder.
Adenocarcinoma↗