Serum alkaline phosphatase activity is not a marker for neoplastic transformation of esophageal nodules in canine spirocercosis.

BACKGROUND: Spirocerca lupi is a nematode of Canidae that matures within the esophageal wall to form fibroblastic nodules with potential for malignant transformation. Diagnosis is based on histopathologic examination, but false-negative results may be obtained from samples collected by endoscopy. Serum alkaline phosphatase (ALP) activity, frequently increased in hepatobiliary disease, is also increased in a variety of neoplastic conditions in dogs, including appendicular osteosarcoma, and has also been reported to be increased in dogs with spirocercosis. OBJECTIVE: The aim of this study was to evaluate serum ALP activity as a marker for malignant transformation of esophageal nodules in S. lupi-infected dogs. METHODS: In this retrospective study, medical records of dogs diagnosed with spirocercosis from 1991 to 2008 were reviewed, and serum ALP activity determined at presentation was compared between dogs with nonneoplastic and neoplastic nodules. Owing to use of multiple analyzers, ratios of ALP activity to the upper reference interval for ALP were calculated and compared. RESULTS: Median ALP activity ratios were 0.65 (0.07-4.00) and 0.86 (0.10-3.40) for dogs with nonneoplastic (n=88) and neoplastic (n=32) nodules, respectively, with no significant difference (P=.18) and substantial overlap between groups. Tumors included osteosarcoma (15 dogs), fibrosarcoma (15 dogs), and anaplastic sarcoma (2 dogs); there was no difference in ALP activity between the dogs with osteosarcoma and fibrosarcoma. CONCLUSION: ALP is a poor marker of malignant transformation in canine spirocercosis.

p53 protein accumulation, iodine-unstained lesions, and alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotypes in Japanese alcoholic men with esophageal dysplasia.

Inactive heterozygous aldehyde dehydrogenase-2 (ALDH2(*)1/(*)2) and less-active alcohol dehydrogenase-1B (ADH1B(*)1/(*)1) increase the risk of esophageal cancer in East Asian drinkers, and esophageal cancer multiplicity is strongly associated with ALDH2(*)1/(*)2. p53 alterations are key molecular events in multifocal carcinogenesis in the esophagus. We studied 260 esophageal-cancer free Japanese alcoholics with esophageal dysplasia diagnosed by biopsy of distinct iodine-unstained lesions (DIULs) ≥5mm. The degree of p53 protein accumulation was positively associated with the degree of atypia (p<0.0001) and size (p=0.040) of DIULs and with the presence of multiple DIULs (p=0.070), but not with ALDH2(*)1/(*)2 or ADH1B(*)1/(*)1.

[Modern esophageal surgery and late functional results as equations with several unknowns--Hungarian Academy of Sciences Doctoral Thesis]. / A modern nyelôcsôsebészet és a késôi funkcionális eredmények "többismeretlenes egyenlete"--MTA Doktori Pályázat.

Using the same surgical method and anatomically ideal primary healing, the functional results could even be different later. Trying to identify various factors being responsible for the above differences, 637 patient's data, who underwent previous oesophago-gastric surgery between 1985-2005, were analyzed. Biochemical, histological and electrophysiological examinations had been evaluated. Developing hypertrophy-like metabolic changes and enteric ganglionitis as morphological alternations of LES muscles induced by GERD may be reasons for complaints after antireflux surgery. The marking of Z-line with endoscopic clips followed by an immediately upright contrast study and substractional evaluation is appropriate for detecting true short esophagus. Open surgical procedures are justified even in the new millennium in cases when the patient already underwent previous upper abdominal operations - due to an increased risk of injury because of adhesions - in cases of primarily recurrent paraesophageal hernias after an unsuccessful open and/or laparoscopic reconstruction, as well as in cases of reflux with complications. When adenocarcinomas of the gastro-oesophageal junction are examined preoperatively, the ratio of the performed catabolic - AMAN, CB, and DPP I - enzymatic activity of the tissue sample from the tumour and adjacent intact mucosa within 2 cm of the tumour may have a prognostic value even in the preoperative examination period, and neo-adjuvant treatment should be considered in these group of patients. The patients' post-operative complaints and symptoms change during the post-operative period and correlate with the parameters of the myoelectric and contractile activities of the "Akiyama stomach". Tachygastria seems to be the major pathogenetic factor involved in the contractile dysfunction. Gastro-jejuno-duodenal interposition represents an adequate 'second-best' method of choice if technical difficulties emerge with jejunal or colon interposition following limited resection of the oesophagus performed due to early Barrett's carcinoma or non-dilatable peptic stricture.

Over-expression of cyclooxygenase-2 in endoscopic biopsies of ectopic gastric mucosa

Ectopic gastric mucosa (EGM) is considered to be a congenital condition. Rare cases of adenocarcinoma have been described. There are no data justifying regular biopsies or follow-up. Cyclooxygenase-2 (COX-2) is a protein involved in gastrointestinal tumor development by inhibiting apoptosis and regulating angiogenesis. The aim of this prospective study was to evaluate COX-2 expression in EGM and compare it with normal tissue and Barrett's esophagus. We evaluated 1327 patients. Biopsies were taken from the inlet patch for histological evaluation and from the gastric antrum to assess Helicobacter pylori infection. Biopsies taken from normal esophageal, gastric antrum and body mucosa and Barrett's esophagus were retrieved from a tissue bank. EGM biopsies were evaluated with respect to type of epithelium, presence of H. pylori, and inflammation. COX-2 was detected by immunohistochemistry using the avidin-biotin complex. EGM islets were found in 14 patients (1.1 percent). Histological examination revealed fundic type epithelium in 58.3 percent of cases, H. pylori was present in 50 percent and chronic inflammation in 66.7 percent. Expression of COX-2 was negative in normal distal esophagus, normal gastric antrum and normal gastric body specimens (10 each). In contrast, EGM presented over-expression of COX-2 in 41.7 percent of cases and Barrett's esophagus in 90 percent of cases (P = 0.04 and 0.03, respectively). COX-2 immunoexpression in EGM was not related to gender, age, epithelium type, presence of inflammation or intestinal metaplasia, H. pylori infection, or any endoscopic finding. Our results demonstrate up-regulation of COX-2 in EGM, suggesting a possible malignant potential of this so-called harmless mucosa.

Over-expression of cyclooxygenase-2 in endoscopic biopsies of ectopic gastric mucosa.

Ectopic gastric mucosa (EGM) is considered to be a congenital condition. Rare cases of adenocarcinoma have been described. There are no data justifying regular biopsies or follow-up. Cyclooxygenase-2 (COX-2) is a protein involved in gastrointestinal tumor development by inhibiting apoptosis and regulating angiogenesis. The aim of this prospective study was to evaluate COX-2 expression in EGM and compare it with normal tissue and Barrett's esophagus. We evaluated 1327 patients. Biopsies were taken from the inlet patch for histological evaluation and from the gastric antrum to assess Helicobacter pylori infection. Biopsies taken from normal esophageal, gastric antrum and body mucosa and Barrett's esophagus were retrieved from a tissue bank. EGM biopsies were evaluated with respect to type of epithelium, presence of H. pylori, and inflammation. COX-2 was detected by immunohistochemistry using the avidin-biotin complex. EGM islets were found in 14 patients (1.1%). Histological examination revealed fundic type epithelium in 58.3% of cases, H. pylori was present in 50% and chronic inflammation in 66.7%. Expression of COX-2 was negative in normal distal esophagus, normal gastric antrum and normal gastric body specimens (10 each). In contrast, EGM presented over-expression of COX-2 in 41.7% of cases and Barrett's esophagus in 90% of cases (P = 0.04 and 0.03, respectively). COX-2 immunoexpression in EGM was not related to gender, age, epithelium type, presence of inflammation or intestinal metaplasia, H. pylori infection, or any endoscopic finding. Our results demonstrate up-regulation of COX-2 in EGM, suggesting a possible malignant potential of this so-called harmless mucosa.

Comparison of glutathione S-transferase-Pi expression at mRNA levels in oesophageal mucosa using RT-PCR-ELISA in individuals with reflux diseases, adenocarcinoma and squamous cell carcinoma.

OBJECTIVES: To develop a RT-PCR technique coupled with Enzyme Linked Immunosobant Assay (ELISA) i.e. RT-PCR-ELISA for measurement of class-Pi glutathione S-transferase (GST-P)-specific mRNA in esophageal diseases. METHODS: In this study, 66 esophageal tissue biopsies diagnosed as non-erosive reflux disease (NERD), gastroesophageal reflux disease (GERD), adenocarcinoma (ADC), and squamous cell carcinoma (SCC) were used. Standardization of the RT-PCR-ELISA was carried out using specific GST-Pi and beta-actin primers, biotin labeled probe, DIG-labeling RT-PCR and anti-DIG-HRP conjugate. RESULTS: The results of RT-PCR-ELISA based on OD ratio of GST-Pi mRNA/beta-actin showed that there was no significant difference in GST-Pi expression in normal, NERD and GERD samples. Overexpression of GST-Pi in malignant tissues (ADC and SCC) was distinguishable. The OD ratio of GST-Pi mRNA expression to beta-actin mRNA was 1.17+/-0.13 and 1.3+/-0.13 in ADC and SCC samples, respectively, which is significantly higher (P<0.05) than matching control (0.78+/-0.06 and 0.85+/-0.07). CONCLUSIONS: RT-PCR-ELISA showed that GST-Pi expression was not altered in GERD and NERD esophagus, whereas, in ADC and SCC samples, it was significantly higher (P<0.05) as compared to inflamed and normal tissues.

Esophageal ATP synthase and keratinocyte growth factor gene expression changes after acid and bile-induced mucosal damage.

OBJECTIVE AND DESIGN: Intramural gene expression changes may be critically involved in tissue damage, defense and repair after esophageal regurgitation. The aims were to characterize the consequences of short-term exposure to luminal bile, acid, or bile mixed with acid on the beta-ATPase, keratinocyte growth factor 1 (KGF-1) and KGF receptor (KGF-R) expressions within the mucosa and the muscle layer in a large animal model. MATERIALS AND SUBJECTS: Esophageal segments of anesthetized dogs were exposed to saline (n = 3), diluted canine bile (n = 6), hydrochloric acid (n = 5) or bile + hydrochloric acid (n = 5), and tissue biopsies were taken at the end of the 180-min observation period. Semiquantitative reverse transcriptase polymerase chain reactions were carried out and the degree of histological damage was evaluated on the 0-16-grade Geisinger scoring scale. RESULTS: Acid exposure was followed by a significant decrease in the level of beta-ATPase expression in the mucosa, and parallel increases in KGF-1 and KGF-R expression. Corresponding changes in the muscle layer were not significant. Bile alone evoked more severe tissue damage, with significantly decreased beta-ATPase levels in both the mucosa and the muscle, whereas the KGF-1 expression did not change significantly. The bile + acid treatment induced an intermediate state, with significant beta-ATPase transcription level decreases in both layers, while the mucosal KGF-1 expression was lower than that following acid treatment alone. CONCLUSIONS: The acid-induced transcriptional level downregulation of mucosal beta-ATPase gene expression in the smooth muscle layer was exacerbated by bile, but the concomitant KGF and KGF-R gene expression changes may indicate the start of a consecutive repair process.

Expression of cyclooxygenase-2 (COX-2) in human esophageal cancer and in vitro inhibition by a specific COX-2 inhibitor, NS-398.

BACKGROUND: The purpose of the present paper was to study the expression of cyclooxygenase-2 (COX-2) in normal squamous epithelium, squamous dysplasia and squamous cell carcinoma (SCC) of the esophagus, to elucidate the role of COX-2 in esophageal carcinogenesis, and to evaluate the in vitro effect and mechanism of a COX-2 inhibitor, NS-398, in inducing growth inhibition and apoptosis of human esophageal cancer cells. METHODS: Biopsy specimens of esophageal dysplasia (n = 21), and surgical resections of SCC (n = 37) were compared with normal esophagus (n = 37) and analyzed by RT-PCR. Human esophageal cells were used for the study. Anti-proliferative effect was measured by MTT, apoptosis was determined by DNA fragmentation assay. RESULTS: Marked COX-2 expression was shown in SCC and esophageal squamous dysplasia, and no marked COX-2 expression was observed in the normal squamous epithelium, respectively. NS-398 could inhibit esophageal cells growth in a dose-dependent manner, induce apoptosis, and elevate caspase-3 activity in vitro. CONCLUSIONS: This study provides evidence that COX-2 is upregulated in the majority of cases of squamous dysplasia and SCC of esophagus, and that NS-398 can inhibit growth and induce apoptosis via activating caspase-3 activity in vitro. These results suggest that selective inhibitors of COX-2 may be an effective preventive and therapeutic option for esophageal carcinoma.

Telomerase activity and expression of telomerase genes in squamous dysplasia and squamous cell carcinoma of the esophagus.

BACKGROUND: Telomerase maintains telomere length and is considered to be necessary for the indefinite proliferation of human cells. Activation of telomerase plays a key role in the malignant transformation process. The aim of this study was to study the regulation of telomerase, and to explore the possibility of telomerase as a biomarker in squamous carcinogenesis of the esophagus. METHODS: Twenty-nine esophageal squamous cell carcinomas (ESCC) and its corresponding adjacent normal tissues, and 47 epithelial squamous dysplasia tissues were analyzed by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique for the mRNA expression of three major telomerase subunits: human telomerase RNA (hTR), telomerase protein component 1 (TP1), and human telomerase reverse transcriptase (hTERT) and by telomeric repeat amplification protocol assay (TRAP) for telomerase activity. RESULTS: For the expression of hTR and TP1 mRNA, there were no significant differences among ESCC, dysplasia and normal tissues (P > 0.05). In contrast, hTERT mRNA expression was detected in 28 of 29 ESCC (96.6%), in 23 of 47 dysplasia (48.9%), and only in two of 29 normal tissues (7.5%). Telomerase activity was positive in 25 of 29 ESCC (86.2%), in 21 of 47 (44.7%) epithelial dysplasia tissues, and in none of normal tissue. All together, 95 of 105 cases (90.48%) were concordant for both results, i.e., telomerase activity positive and hTERT positive or telomerase activity negative and hTERT negative tissues, and telomerase activity correlated with hTERT mRNA expression (P < 0.001). CONCLUSIONS: Higher telomerase activity and hTERT mRNA expression were shown during an early stage in the esophageal carcinogenesis. Activation of telomerase activity was strongly correlated with hTERT mRNA expression, suggesting hTERT is a major regulator of telomerase activity, and telomerase activation may play a critical role in esophageal carcinogenesis. Therefore, telomerase, especially hTERT can be used as a potential molecular biomarker of ESCC.

Benznidazole-induced ultrastructural and biochemical alterations in rat esophagus.

Benznidazole (Bz) is a drug used in the chemotherapy of the acute and intermediate phases of Chagas' disease (American Trypanosomiasis), an endemic parasitic disease afflicting more than 16 million people in Latin America. Serious toxic side effects of Bz have been reported in treated human beings and in experimental animals. Bz toxicity would be linked to its nitroreductive bioactivation to reactive intermediates and to the corresponding amine known to occur in vivo and mediated by different enzymatic systems. In the present study the presence of Bz nitroreductases in rat esophagus and the occurrence of Bz induced esophageal cell injury are described. Already 1 and 3 h after an intragastric Bz administration to Sprague-Dawley male rats (240-260 g body weight) at a dose of 100 mg/kg esophageal levels of the drug were 66.4+/-4.0 and 149.2+/-14.3 nmol per g tissue, respectively. The esophageal mucosa homogenates exhibited Bz nitroreductase activity attributable to the participation of cytochrome P450 reductase and xanthine oxidoreductase (XOR). The ultrastructural observation of esophageal tissue from Bz treated animals 24 h after its administration evidenced: detachment and conglomeration of polyribosomes, reduction in the presence of desmosomes and of the amount of bacteria on its surface. The potential significance of these alterations is not fully clear at present. However, these deleterious effects might be additive or synergistic with those induced by the evolution of the disease.

Telomerase activity and expression of human telomerase catalytic subunit gene in esophageal tissues.

BACKGROUND: Telomerase, the ribonucleoprotein enzyme that synthesizes telomeric DNA, is thought to be necessary for cellular immortality and carcinogenesis. Telomerase activity is associated with the majority of malignant human cancers. The mRNA that encodes the telomerase catalytic subunit (human telomerase repeat transcriptase; hTERT) has recently been identified, and the expression of the hTERT gene is thought to regulate the activation of telomerase. However, the expression of hTERT mRNA in esophageal tissues has not been reported. We investigated hTERT gene expression in cancerous and noncancerous esophageal tissues, and determined the relationship between hTERT mRNA expression and telomerase activity. METHODS: Tissues from esophageal carcinomas in 14 patients, reflux esophagitis in 12 patients, esophageal acanthosis in 2 patients, esophageal papilloma in 1 patient, radiation esophagitis in 1 patient, and normal esophageal epithelium in 11 patients (including 3 specimens of normal epithelium from patients with esophageal carcinoma) were examined. All specimens were taken endoscopically. hTERT gene expression was investigated using reverse transcription-polymerase chain reaction (RT-PCR). Quantitative analysis of telomerase activity was analyzed by fluorescence telomeric repeat amplification protocol (F-TRAP) assay. RESULTS: Thirteen of the 14 (93%) esophageal carcinoma specimens expressed hTERT mRNA and revealed detectable telomerase activity. Noncancerous esophageal lesions had not only hTERT mRNA expression with a high frequency (14 of 16 cases; 88%) but also detectable telomerase activity (12 of 13 cases; 92%). Normal esophageal epithelium also highly expressed hTERT mRNA (10 of 11 cases; 91%) and revealed detectable telomerase activity (all 9 cases; 100%). In 32 of the 35 specimens analyzed for both hTERT mRNA and telomerase activity (91%), the expression of hTERT mRNA was consistent with detectable telomerase activity. CONCLUSIONS: The expression of hTERT mRNA was detected not only in cancerous but also in noncancerous esophageal tissues at a high frequency. This result was different from that reported for other gastrointestinal epithelium. Moreover, telomerase activity in esophageal carcinoma was significantly stronger than that in reflux esophagitis and normal epithelium. In addition, there was a strong relation ship between the detection of telomerase activity and the expression of hTERT mRNA in cancerous and noncancerous esophageal tissues. Thus, the qualitative analysis of hTERT mRNA expression may not be useful as a biomarker of carcinoma in esophageal tissues. Nevertheless, the quantitative analysis of telomerase activity may be somewhat useful.

Reduced Fhit expression occurs in the early stage of esophageal tumorigenesis: no correlation with p53 expression and apoptosis.

The FHIT gene, encompassing the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene involved in multiple tumors, including esophageal carcinoma. We analyzed Fhit expression using an immunohistochemical method in invasive carcinoma, carcinoma in situ (CIS) and dysplasia, in paraffin sections of 75 esophageal squamous cell carcinomas (ESCs) to further elucidate the role of Fhit protein in esophageal carcinogenesis. In addition, we also examined whether Fhit expression correlated with p53 expression and apoptosis. Compared to adjacent normal mucosa, significant loss or reduction of Fhit expression was noted in 67 of 75 (89.3%) invasive ESCs, in 13 of 19 (68.4%) CIS lesions, and in 10 of 23 (43.5%) dysplastic lesions. There was a progressive loss or reduction of Fhit expression with progressive increases in the severity of histopathological changes (p < 0.001). However, there was no association between Fhit expression and clinicopathological findings, including tumor stage, lymph node metastasis, or overall survival. Moreover, Fhit expression was not significantly associated with p53 expression and apoptosis. These results indicate that abnormal Fhit expression is a common event in the early stage of ESC development and may occur independently of p53 expression and apoptosis mechanisms.

Eicosanoids and the esophagus.

Eicosanoids are products of arachidonic acid metabolism. Among the products produced are the prostaglandins and leukotrienes, products which are known to play important roles in health and disease of many gastrointestinal tissues. Here, we review current knowledge about eicosanoids in the esophagus, including production in healthy and diseased tissues and potential physiologic and pathophysiologic effects in two important esophageal mucosal disorders, reflux esophagitis and esophageal cancer.

Topoisomerase II alpha expression in esophageal squamous cell carcinoma.

BACKGROUND: DNA topoisomerase II alpha (topo II alpha) is associated with active cell proliferation of mammalian cells. Topo II alpha overexpression has been reported in a number of human malignancies and is considered to be related to their biological behaviors. MATERIALS AND METHODS: We examined the expression of topo II alpha immunohistochemically in 136 cases of human esophageal squamous cell carcinoma, 10 foci of squamous dysplasia and 10 non-pathologic squamous epithelium. We calculated the labeling index (LI) or the percentage of immunopositive cells for Topo II alpha and Ki67, and Topo II alpha LI/Ki67 LI (T/K ratio). These findings were then correlated with clinicopathological features of the patients including their clinical outcome. RESULTS: Both topo II alpha and Ki67 immunoreactivity were detected in the nuclei. A significant positive correlation was obtained between Topo II alpha and Ki67 LIs in all the specimens examined. Topo II alpha LI and T/K ratio were 24.5 +/- 8.0% and 1.04 +/- 0.64 for carcinoma, 19.1 +/- 15.2% and 0.68 +/- 0.29 for dysplasia and 14.0 +/- 14.1% and 0.55 +/- 0.17 for non-pathologic epithelium, respectively. Topo II alpha LI and T/K ratio in carcinoma cases were significantly higher than those of normal epithelium. Topo II alpha LI alone did not correlate with any of clinicopathological parameters examined but among carcinoma cases, cases with lymph nodes metastasis or higher histological stages had significantly higher T/K ratio than those without lymph node metastasis or lower histological stages. In addition, carcinoma cases with T/K ratio of greater than 0.8 demonstrated significantly worse prognosis than those with T/K ratio of smaller than 0.8. CONCLUSIONS: The relative overexpression of topo II alpha as compared with Ki67, i.e., increased T/K ratio was detected in esophageal squamous cell carcinoma and is considered to represent a dysregulation or qualitative alteration in topo II alpha, possibly associated with malignances, as reported in other human cancers. In addition, topo II alpha overexpression may also be correlated with the aggressive biological behavior of the patients with esophageal squamous cell carcinoma.

Ornithine decarboxylase activity in Barrett's esophagus: a potential marker for dysplasia.

Ornithine decarboxylase activity is known to be increased in certain premalignant conditions. We determined the activity of this enzyme in mucosal biopsy specimens from 15 patients with Barrett's esophagus. Ornithine decarboxylase was greater in Barrett's mucosa than in squamous esophageal or gastric mucosa. In Barrett's mucosa from 4 patients with dysplasia, the enzyme activity was greater than in 11 patients without dysplasia (1.6 +/- 0.35 vs. 0.19 +/- 0.08 U/mg protein; p less than 0.005). Increased ornithine decarboxylase activity in biopsy specimens of Barrett's mucosa may represent a marker for dysplasia.

Immunohistochemical localization of pepsinogen A and C containing cells in Barrett's oesophagus.

No data are available on the localization of Pepsinogen A (PGA = PG I) and Pepsinogen C (PGC = PG II) positive cells in Barrett's epithelium. Endoscopic biopsy specimens were taken from the columnar epithelium from 23 patients (n = 93), and in addition from the cardia from eight healthy control subjects (n = 38). The tissue was stained by the immunoperoxidase technique with specific anti-pepsinogen antisera, and double immunostained for PGA and PGC. In the Barrett's epithelium PGA was found in 28 out of 93 biopsy specimens (30.1%) and PGC in 55 out of 93 (59.1%). Chief cells always stained both for PGA- and PGC +. PGA + and PGC + cells were found each in 100% of the biopsy specimens with fundic type epithelium, in 21.7% and 70.7% of biopsy specimens with junctional type, in 0% and 26.1% of biopsy specimens with specialized epithelium and in 12.5% and 43.5% of biopsy specimens with mixed junctional/specialized features respectively. Dysplastic epithelium stained always negatively with both anti-pepsinogen antisera. In most control cardia biopsy specimens PGA as well as PGC were demonstrable; occasionally clear mucous glands were PGA - and PGC+. It is concluded that pepsinogen-containing cells can be accurately identified in the Barrett's epithelium; their presence seems related to the histological cell type. Identification of pepsinogen positive cells may contribute to a more accurate morphological classification of the Barrett's epithelium.

Gastric proteases in Barrett's esophagus.

Precursors of the gastric proteases pepsinogen A (pepsinogen I) and pepsinogen C (pepsinogen II) and slow-moving protease were demonstrated in biopsy specimens from Barrett's epithelium in 21 of 22 patients with Barrett's esophagus; in 14 of them, in variable combinations at different sites. In 13 of 19 patients (68.4%) with detectable pepsinogen A, different isozymogen patterns were found between the Barrett's epithelium and the gastric corpus mucosa. Discrepancies consisted mainly of a stronger pepsinogen 5 band in the Barrett's epithelium, with a higher incidence in biopsy specimens with features of dysplasia than with no or indefinite dysplasia; the difference was, however, not statistically significant. Zymograms of 69 biopsy specimens from Barrett's epithelium were correlated with the histologic type: pepsinogen A and C were most frequently found in the fundic type, least often in the specialized intestinal type. In control gastric corpus biopsy specimens, pepsinogen A and C as well as slow-moving protease were always detectable. The observed variability of gastric protease patterns, in particular of pepsinogen A isozymograms, may be due to differences in expression within the pepsinogen A cluster, suggesting a deregulation of gene expression or partial deletion of the pepsinogen A gene cluster.

Esophageal columnar epithelial beta-galactosidase and beta-glucuronidase.

We have compared the activity of the lysosomal enzymes, beta-galactosidase and beta-glucuronidase, in esophageal columnar, gastric fundic, and small intestinal epithelia. Beta-Galactosidase activity in esophageal columnar epithelium was less than that in intestinal tissue. Beta-Glucuronidase activity in the esophageal columnar epithelium was greater than that in gastric fundic tissue. Thus, this unique epithelium has enzyme characteristics which are dissimilar to both intestinal and gastric fundic tissue. This tends to support previous findings that suggested a metaplastic derivation.