In order to elucidate the dynamic changes of oncogene expression in the sequential cascade of squamous metaplasia, dysplasia, and squamous cell carcinoma of the bronchial epithelium, hybridization in situ was employed with a biotinylated oncogene probe. The expression of c-myc was localized exclusively in nuclei. While normal bronchial epithelium revealed no discernible clumps of c-myc grains, except occasional grains less than 3 per cell, squamous metaplasia showed increased number of grains and a few clusters of c-myc grains. In dysplasia, c-myc expression was more intensive than in squamous metaplasia. Approximately, 1/3 to 2/3 of tumor cell populations of squamous cell carcinomas of the lung revealed tremendously increased c-myc expression. In addition clumpy grains of c-myc in squamous cell carcinoma appeared more frequently than in squamous metaplasia or dysplasia. The c-myc expression was found to vary between different samples and within each cancer, and not all cancer cells expressed c-myc. These data indicate that c-myc oncogene plays it's role on reprogramming for growth control of cell populations particularly in multistage carcinogenesis and progression of lung cancer. These dynamic alterations of c-myc expression suggest that neoplastic transformation may occur conceivably at the dysplastic phase eventually resulting in carcinoma in situ. This means, in turn, squamous dysplasia is a putative precancerous lesion of the human lung.
Bronchial Neoplasms/*genetics/pathology ; Carcinoma, Squamous Cell/*genetics/pathology ; Cell Transformation, Neoplastic/*genetics ; DNA ; Humans ; Metaplasia ; Nucleic Acid Hybridization ; *Oncogenes

To investigate the potential implication of the subtype of intestinal metaplasia in the progression to the gastric carcinoma, we analyzed the mutations of the p53 gene and microsatellite instability (MSI) both in the complete type (type I) and in the sulphomucin-secreting incomplete type (type III) intestinal metaplasia located adjacent to the gastric carcinoma. p53 mutations were observed in 13.3% of type I, in 6.6% of type III intestinal metaplasia, and in 40% of gastric carcinoma. The difference between p53 mutations observed in type I and type III intestinal metaplasia was not statistically significant. No identical mutation of the p53 gene was found in the intestinal metaplasia and carcinoma specimens from the patients. There was no case of intestinal metaplasia showing MSI. In gastric carcinomas, MSI was observed in six cases (40%). The cases harboring BAT-26 instability did not have the mutation of the p53 gene. These data suggest that intestinal metaplasia adjacent to gastric carcinoma, irrespective of its subtype, do not have the genetic alterations as showing in their carcinoma tissues.
Carcinoma/genetics/pathology ; Exons ; *Genes, p53 ; Humans ; Metaplasia/genetics/pathology ; *Microsatellite Repeats ; *Mutation ; Precancerous Conditions ; Stomach/*pathology ; Stomach Neoplasms/genetics/pathology ; Tumor Suppressor Protein p53/genetics/metabolism

Animals ; Carcinoma, Pancreatic Ductal ; genetics ; pathology ; Genes, ras ; genetics ; Humans ; Metaplasia ; MicroRNAs ; genetics ; Mutation ; Pancreatic Ducts ; pathology ; Pancreatic Neoplasms ; genetics ; pathology ; Pancreatitis ; genetics ; Signal Transduction

No abstract availble.
Gastritis, Atrophic/*genetics/metabolism ; *Gene Expression Profiling ; Humans ; Intestines/metabolism/*pathology ; Metaplasia/genetics/metabolism ; *Microarray Analysis ; Tumor Markers, Biological/metabolism

BACKGROUND/AIMS: The atrophic gastritis with intestinal metaplasia of gastric mucosa has been considered to be the major factor of carcinogenesis in the stomach. However, the key molecules are still poorly understood. To elucidate the molecular genetic basis, we report the results of our initial microarray data to analyze the genome pattern in patients with atrophic gastritis and intestinal metaplasia of the stomach. METHODS: We used oligonucleotide microarray technique to evaluate the gene expression profiles in atrophic gastritis with intestinal metaplasia, in comparison with those of normal mucosa. For the identification of differentially expressed genes, Significance Analysis of Microarrays (SAM) package method was used. The results were analyzed using global normalization, intensity dependent normalization, and box plot normalization. RESULTS: Eight genes including FABP, REG, OR6C1, MEP1, SLC6A1, SI, Mucin 1, and RAB23 in mucosa of atrophic gastritis and intestinal metaplasia were up-regulated by more than 10 times as compared with normal gastric mucosa. Only one gene, LOC44119 was down-regulated by more than 10 times of the expression as compared with normal gastric mucosa. In respect to the expression of known genes related to gastric carcinogenesis, 8 genes including FN1, SRMS, TP53, TP53IMP2, TP53I3, FGFR4, TGFB1, and TGFA showed up- and down-regulations more than 2 folds in expression pattern. CONCLUSIONS: We could identify a total genome pattern in patient with atrophic gastritis and intestinal metaplasia using oligonucleotide microarray. We believe that the current results will serve as a fundamental bioinformative basis for clinical applications in diagnosis and treatment of gastric cancer and precancerous lesion in the future.
Down-Regulation ; Gastritis, Atrophic/*genetics/metabolism ; Gene Expression Profiling ; Humans ; Intestines/*metabolism/*pathology ; Metaplasia/genetics/metabolism ; Microarray Analysis ; Tumor Markers, Biological/genetics/metabolism ; Up-Regulation

OBJECTIVETo study the cytokeratin 18 and 13 and their gene (CK) expression in post-operation maxillary cyst linings with metaplastic epithelium.

METHODSCK expressions were examined with immunohistochemistry in 46 post-operative maxillary cyst (POMC) which were lined with pseudostriated columnar cells only (13 cases), both kinds of columnar and squamous cells (30 cases) and squamous cells only (3 cases).

RESULTSThe expressions of CK8, CK13 and CK18 were observed in 39, 9 and all of the 43 columnar epithelial linings, respectively. Metaplastic squamous epithelia expressed more CK13 and less CK18 and CK8. Of the 33 metaplastic linings, 24 expressed CK8, 23 CK13 and 26 linings expressed CK18. The expression of CK13- and CK18-mRNA was generally correlated with the protein expression level. By in situ hybridization, CK18-mRNA expression was observed not only in 26 metaplastic linings which were positive for CK18 protein but also in five of the seven metaplastic linings which did not express CK18 protein. In addition, RT-PCR revealed an expression of CK18-mRNA in all metaplastic squamous linings although the expression level was weaker than that in the columnar epithelial linings. The CK13-mRNA was expressed in a fashion inverse to the CK18-mRNA.

CONCLUSIONSThese results indicate that CK18-mRNA is preserved through metaplasia although the protein expression decreases and metaplastic squamous cells differentiate with a decrease of CK18 and an increase of CK13 expression.

Epithelial Cells ; metabolism ; pathology ; Humans ; Jaw Cysts ; etiology ; metabolism ; pathology ; Keratin-13 ; biosynthesis ; genetics ; Keratin-18 ; biosynthesis ; genetics ; Maxillary Diseases ; etiology ; metabolism ; pathology ; Metaplasia ; metabolism ; pathology ; Postoperative Complications ; RNA, Messenger ; genetics

OBJECTIVETo evaluate the effect of IL-1beta on the expression of CDX2 in human gastric epithelial cell line GES-1 and its role in the intestinal metaplasia.

METHODSGES-1 cells were treated with IL-1beta in different concentrations and the expressions of CDX2 mRNA and protein were detected by real-time PCR, immunocytochemistry and Western blot at different time points. GES-1 cells were then pre-treated with NF-KappaB pathway inhibitor PDTC, and the expression of CDX2 mRNA and protein induced by IL-1beta were detected. The cell ultra-structure of GES-1 cells was observed by electronic microscope after GES-1 being treated with IL-1beta for 25 days.

RESULTSLevels of CDX2 mRNA and protein were 0.0749 + or - 0.0021 and 0.56 + or - 0.04 in the cells treated with 1 microg/L IL-1beta(P<0.05). After pre-treatment with PDTC, levels of CDX2 mRNA and protein were 0.0006 + or - 0.0002 and 0.40 + or - 0.06(P<0.05). Some changes in the cell ultra-structure of GES-1 were found by electronic microscope when GES-1 was treated with IL-1beta for 25 days.

CONCLUSIONIL-1beta can stimulate CDX2 mRNA and protein expression in GES-1 cells through the NF-KappaB signal pathway, indicating that IL-1beta plays an important role in the intestinal metaplasia.

CDX2 Transcription Factor ; Cell Line ; Epithelium ; metabolism ; pathology ; Gastric Mucosa ; cytology ; metabolism ; pathology ; Homeodomain Proteins ; metabolism ; Humans ; Interleukin-1beta ; pharmacology ; Metaplasia ; RNA, Messenger ; genetics

Intestinal metaplasia (IM) has been regarded as a premalignant condition. However, the pathogenesis of IM is not fully understood. The aim of this study was to evaluate the role of CDX1 and CDX2 in the formation of IM and the progression to dysplasia and gastric cancer (GC). A total of 270 subjects included 90 with GC, dysplasia and age- and sex-matched controls. Real-time PCR (RT-PCR) was performed with body specimens for CDX1 and CDX2. The expression of CDX2 was significantly higher in H. pylori positive group than H. pylori negative group (P = 0.045). CDX1 and CDX2 expression increased proportional to the IM grade of the body (P < 0.001). CDX2 expression was significantly higher in incomplete type of IM than in complete type (P = 0.045). The expression of CDX1 in dysplasia group was significantly higher than in the control group (P = 0.001); in addition, CDX1 and CDX2 in cancer group was significantly higher than control group (P < 0.001, and P < 0.001, respectively). Aberrant expression of CDX1 and CDX2 correlated with H. pylori infection and grade of IM in the body. Furthermore, the results suggest that CDX1 and CDX2 play a role in the progression to GC and dysplasia.
Aged ; Female ; Helicobacter Infections/complications/microbiology ; Helicobacter pylori/isolation & purification ; Homeodomain Proteins/*genetics/metabolism ; Humans ; Intestinal Diseases/*genetics/microbiology/pathology ; Male ; Metaplasia/pathology ; Middle Aged ; Polymerase Chain Reaction ; Precancerous Conditions/metabolism/pathology ; Stomach Neoplasms/etiology/*genetics/microbiology

OBJECTIVETo evaluate the relationship between mitochondrial DNA instability (mtMSI) and interleukin-8 (IL-8) activity in gastric mucosa of various lesions.

METHODSIL-8 level in gastric mucosa was assayed using ELISA method. The mtMSI was detected by PCR-SSCP techniques.

RESULTSmtMSI was observed in 11 out of 30 (36.7%) gastric cancers, 2 of 15 (13.3%) intestinal metaplasia, 2 of 10 dysplasia and 1 of 10 chronic atrophic gastritis. IL-8 level in mtMSI+ group [(76.8 +/- 3.8) pg/mg] was significantly higher than that in mtMSI- group [(48.3 +/- 3.6) pg/mg, P < 0.05].

CONCLUSIONmtMSI closely correlates with IL-8 level in gastric mucosa and is involved in gastric carcinogenesis.

DNA, Mitochondrial ; genetics ; Enzyme-Linked Immunosorbent Assay ; Gastric Mucosa ; metabolism ; pathology ; Gastritis, Atrophic ; genetics ; metabolism ; Genomic Instability ; Humans ; Interleukin-8 ; metabolism ; Metaplasia ; genetics ; metabolism ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Precancerous Conditions ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; metabolism

Objective: To study the clinicopathologic and genetic features of papillary cystic low-grade mucoepidermoid carcinoma (LG-MEC) and cystadenoma. Methods: A retrospective review was performed on salivary gland tumor patients with papillary cystic architecture who presented to department of oral pathology, Peking University School and Hospital of Stomatology between January 2010 and June 2022. Among this cohort, there were 17 males and 17 females with a range age of 23-82 years [(55.6±14.6) years]. Diagnosis was confirmed by histological, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis. Finally, 15 papillary cystic LG-MEC and 19 cystadenoma patients were included in the present study. All patients were followed clinically and radiologically, and the duration of follow-up ranged from 1 to 141 months. Results: All neoplasms showed papillary proliferation with multilocular or giant cystic tumors. Papillary cystic LG-MEC was characterized by epidermoid cells, intermediate cell and mucous cells with multiple lining-layers. Papillary cystic LG-MEC had mild cellular atypia and a pushing infiltration. Cystadenoma was characterized by cuboidal, columnar and ciliated pseudostratified columnar lining epithelium. Squamous metaplasia, mucinous metaplasia and acidophilic degeneration could also be observed focally in cystadenoma. For IHC staining, papillary cystic LG-MEC showed diffusely and strongly positive for mucin 4 (MUC4) (15/15) and mucin 5 Subtype AC (MUC5AC) (4/15) in the epidermoid cells, intermediate cell and mucous cells. The epidermoid cells and intermediate cells were diffusely positive for p40 and p63. The Ki-67 index was about 10%-15% in LG-MEC. As a contrast, p40 (17/19) and p63 (14/15) were only detected in the basal cells of cystadenoma. Cystadenoma showed focal MUC5AC (4/19)expression and MUC4 (19/19)diffuse expression. In addition, the Ki-67 index was 5%-10% in cystadenoma. The MAML2 gene translocation was detected in 11 LG-MEC patients, but none in cystadenoma. Conclusions: The differential diagnosis points between papillary cystic LG-MEC and cystadenoma included the specific epidermoid cells, intermediate cells and mucus cells in LG-MEC, cell atypia, the pushing-infiltration pattern, diffuse expression of p40 and p63 in the lining epithelium, and a MAML2 gene rearrangement. The molecular test of MAML2 should be recommended to reduce missed LG-MEC diagnoses.
Male ; Female ; Humans ; Carcinoma, Mucoepidermoid/pathology* ; In Situ Hybridization, Fluorescence ; Ki-67 Antigen/genetics* ; Biomarkers, Tumor/analysis* ; Salivary Gland Neoplasms/diagnosis* ; Transcription Factors/metabolism* ; Cystadenoma ; Metaplasia