Methylation of p16 and hMLH1 genes in esophageal squamous cell carcinoma and reflux esophagitis / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the promoter methylation pattern of p16 and hMLH1 genes in esophageal squamous cell carcinoma and reflux esophagitis, and to correlate the results with clinical and pathologic findings.</p><p><b>METHODS</b>Twelve cases of normal esophagus, 13 cases of esophageal squamous cell carcinoma, 43 cases of reflux esophagitis with basal cell hyperplasia and 21 cases of reflux esophagitis with dysplasia, as confirmed by endoscopic and pathologic examination, were enrolled into the study. Genomic DNA was extracted. The promoter methylation status of p16 was measured by methylation-specific polymerase chain reaction. The promoter methylation status of hMLH1 was measured by sodium bisulfite-restriction enzyme digestion. Immunohistochemical study for p16 and hMLH1 proteins was also carried out.</p><p><b>RESULTS</b>The rates of p16 methylation in normal esophageal epithelium, basal cell hyperplasia, dysplasia and esophageal squamous cell carcinoma were 0/12, 14.0% (6/43), 38.1% (8/21) and 6/13, respectively. The p16 methylation correlated with the progress of esophageal lesions. On the other hand, the hMLH1 methylation was not observed in the normal esophageal epithelium and reflux esophagitis. One case of esophageal squamous cell carcinoma showed the presence of hMLH1 methylation. The hMLH1 promoter hypermethylation did not correlate with the clinical and pathologic features.</p><p><b>CONCLUSIONS</b>The p16 methylation may be one of the earliest events in the pathogenesis of esophageal squamous cell carcinoma and is also observed in reflux esophagitis. Reflux esophagitis may be related to the development of esophageal squamous cell carcinoma in Chinese population. In contrast, hMLH1 methylation may not be directly involved in the tumorigenesis of esophageal squamous cell carcinoma.</p>

Clinicopathologic study of sinonasal teratocarcinosarcoma and its contrast with olfactory neuroblastoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, diagnosis and differential diagnosis of sinonasal teratocarcinosarcoma (SNTCS) and olfactory neuroblastoma (ONB), and to discuss the histogenesis and possible relationship between SNTCS and ONB.</p><p><b>METHODS</b>Seven cases of SNTCS and 34 cases of ONB were retrieved from the pathological archives together with one case each of malignant teratoma and immature embryonic tissue at 8 weeks were collected from Beijing Tongren Hospital. The clinicopathologic features were analyzed and immunohistochemical staining was performed on paraffin sections.</p><p><b>RESULTS</b>Six of the SNTCS patients were male and one was female. The patients age range was 25 to 69 years (mean age 46). Four cases were initial presentation and three were recurrences. Histologically, the tumor shows multiple tissue components derived from three germ layers. There were mixture of teratoma-like tissue and carcinosarcoma. The components include fetal clear cell squamous epithelium derived from ectoderm. Glandular and tubular structures and ciliated columnar epithelium derived from endoderm. Fibroblasts, striated muscle, smooth muscle, cartilage and osteoid matrix derived from mesoderm. The carcinoma component exhibited mostly adenocarcinoma and squamous cell carcinoma, whereas the sarcoma component mostly exhibited rhabdomyosarcoma, leiomyosarcoma, and fibrosarcoma. In addition, carcinoid, and primitive mesenchymal tissue and the ONB component were also seen. The morphological characteristics of SNTCS comprised fetal clear cell squamous epithelium, carcinosarcoma and the ONB component. By immunohistochemistry, the epithelial component and cells with epithelium differentiation were positive for cytokeratin (pan) and EMA. The ONB component was positive for Syn, NSE, CD99, NF and CgA to different degrees. Neurofibril bundles were positive for S-100, and Flexner-Wintersteiner rosettes expressed cytokeratin (pan) and EMA. The spindle cells expressed vimentin, SMA, desmin, myosin and myoglobin. The primitive mesenchymal tissue expressed vimentin, and the mucoid materials and glycogen were positive for PAS. GFAP was negative in all cases. The 34 cases of ONB, included 18 men and 16 women, the age ranged from 12 to 72 years (mean 42.8 years). Microscopically, the tumor shows epithelial nests, net of angioma-like fibrous connective tissues, small round and spindle cells, glandular, squamous-like cells, and cells of rhabdomyoblastic differentiation, Homer-Wright and Flexner rosette, bundles of neurofibrils, etc. NSE and CgA were expressed in small cells. S-100 protein was positive in the areas of bunches of neurofibril. Cytokeratin (pan) was positive in epithelial cells. Myoglobin was positive in the cells of rhabdomyoblastic differentiation. The single case of immature malignant teratoma exhibited primitive nerve tissue, but fetal clear cell squamous epithelium was not found. In the immature embryonic tissue, rudimentary organs were formed, with fetal clear cell squamous epithelium lining present on the nasal and oral cavities surface.</p><p><b>CONCLUSIONS</b>SNTCS is a rare and aggressive malignant neoplasm. Most of ONB are low-grade malignant tumors. Morphological differences are the most important basis to make differentiate SNTCS from ONB. As SNTCS may demonstrate a multiplicity of structures and pleomorphism, inadequate sampling at biopsy, therefore, may lead to errors in diagnosis. No evidence show that SNTCS are derived from germ cells and sinonasal teratoid carcinosarcoma may be a more proper name. SNTCS probably arises from primitive totipotential cells of olfactory/sinonasal membrane, and the relationship between SNTCS and ONB needs further study.</p>

The changes of advanced glycation end products in a rat liver fibrosis model and the interventional effect of aminoguanidin / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the changes of advanced glycation end products (AGEs) in different phases of a rat liver fibrosis model induced by CCl4, and the interventional effect of aminoguanidin (AG).</p><p><b>METHODS</b>Fifty-four SD rats were divided into three groups: a control group, a CCl4 model group and an intervention group. Their blood serum AGEs and hyaluronic acid (HA) and AGEs in their liver homogenates were measured. These measurements were correlatively assessed to the degrees of liver fibrosis at different phases of the rat model before and after the intervention with aminoguanidin.</p><p><b>RESULTS</b>The content of AGEs in their blood sera and liver homogenates, and the level of blood serum HA, and the score of liver fibrosis degree at week 12 in our rat liver fibrosis mode groups were significantly higher than those in the control group (P < 0.01). In the intervention group with aminoguanidin, these figures were lower than those in the liver fibrosis model group (P < 0.05). The content of AGEs in their blood sera and liver homogenates had a linear correlation with the level of HA in their blood sera.</p><p><b>CONCLUSION</b>The contents of AGEs in their blood sera and liver homogenates were increased in the late phase of our rat liver fibrosis model. To some extent, the level of AGEs may reflect the fibrosis degree of the rat livers. Aminoguanidin has an interventional effect in our CCl4 induced rat liver fibrosis model.</p>