A classification of gastric dysplasia

Epithelial dysplasia was studied in 53 surgical specimens of gastric carcinoma and eight gastric adenomas. A spectrum of dysplasia was observed, but there were two principal types. Type I resembled the epithelium lining colonic adenomas whereas type II was composed of eosinophilic cells with basally sited vesicular nuclei. These findings are compared with reports on heterogeneity within both gastric dysplasia and dysplasia in other areas of the gastrointestinal tract. A link is demonstrated between incomplete intestinal metaplasia, type II dysplasia and the more poorly differentiated cancers of intestinal type.     

The chemokine receptor CCR7 is expressed on epithelium of non-inflamed gastric mucosa, Helicobacter pylori gastritis, gastric carcinoma and its precursor lesions and up-regulated by H. pylori

CCR7 chemokine-receptor expression on tumour cells of gastric carcinoma has been associated with lymph-node metastasis and is thought to play an important role in metastasis. However, so far it is unknown whether CCR7 is newly up-regulated on gastric carcinoma or already expressed in non-neoplastic gastric epithelium. Therefore, epithelial CCR7 expression was investigated in the process of gastric carcinogenesis: non-inflamed mucosa --Helicobacter pylori gastritis -- intestinal metaplasia/dysplasia -- gastric carcinoma. CCR7 was expressed by gastric epithelium in non-inflamed gastric mucosa (n = 5), H. pylori gastritis (n = 17), intestinal metaplasia (n = 10), dysplasia (n = 3) and on tumour cells in 20 of 24 patients with gastric carcinoma (13/14 intestinal-type; 7/10 diffuse-type) as tested by immunohistochemistry. As CCR7 expression by gastric epithelium was significantly stronger in H. pylori gastritis than in non-infected mucosa, the influence of H. pylori on CCR7 receptor expression of gastric epithelial cells was investigated by fluorescence activated cell sorter analysis. H. pylori strains up-regulated the CCR7 chemokine-receptor in CCR7-positive cell lines. No difference in CCR7 up-regulation between cag(+) and cag(-)H. pylori strains was found. Epithelial CCR7 up-regulation by H. pylori may alter the metastatic fate of gastric carcinoma. Additionally, CCR7 expression not only on gastric carcinoma, but also on non-neoplastic gastric epithelium, suggests a novel biological function.     

Differential expression of cdk inhibitors p16, p21cip1, p27kip1, and cyclin E in cervical cytological smears prepared by the ThinPrep method

Our objective was to correlate p16, p21cip1, p27kip1, and cyclin E protein expression with the degree of dysplasia on ThinPrep Papanicolaou (Pap) smears using a modified immunoperoxidase staining. Smears read as normal, atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), or high-grade SIL (HSIL) were identified and tested for high-risk human papillomavirus (HR-HPV). Additional smears were processed for immunoperoxidase for p16, p21cip1, p27kip1, and cyclin E. Thirty-four smears were satisfactory for study. The p16 was positive in all nine HSIL, in four of nine LSIL, and in one of seven ASC-US. The p27kip1 was positive in all nine HSIL, in eight of nine LSIL, and in one of seven ASC-US. The p21cip1 was positive in all nine HSIL, in one of nine LSIL, and in one of seven ASC-US. Cyclin E was positive in seven of nine HSIL and in one of nine LSIL and in none of the ASC-US smears. Normal smears were negative for all the antigens. There was poor correlation of protein expression and HR-HPV infection. We concluded that p16, p21cip1, p27kip1, and cyclin E can be demonstrated on Pap smears and they are expressed differentially in dysplastic cells, with highest expression in HSIL. The p21cip1 and cyclin E showed the greatest correlation with HSIL.     

Localisation of the gene causing diaphyseal dysplasia Camurati-Engelmann to chromosome 19q13

Camurati-Engelmann disease, progressive diaphyseal dysplasia, or diaphyseal dysplasia Camurati-Engelmann is a rare, autosomal dominantly inherited bone disease, characterised by progressive cortical expansion and sclerosis mainly affecting the diaphyses of the long bones associated with cranial hyperostosis. The main clinical features are severe pain in the legs, muscular weakness, and a waddling gait. The underlying cause of this condition remains unknown.In order to localise the disease causing gene, we performed a linkage study in a large Jewish-Iraqi family with 18 affected subjects in four generations. A genome wide search with highly polymorphic markers showed linkage with several markers at chromosome 19q13. A maximum lod score of 4.9 (theta=0) was obtained with markers D19S425 (58.7 cM, 19q13.1) and D19S900 (67.1 cM, 19q13. 2). The disease causing gene is located in a candidate region of approximately 32 cM, flanked by markers D19S868 (55.9 cM, 19q13.1) and D19S571 (87.7 cM, 19q13.4).     

Exome sequencing reveals a novel COL2A1 mutation implicated in multiple epiphyseal dysplasia

Mutations in the COMP, COL9A1, COL9A2, COL9A3, MATN3, and SLC26A2 genes cause approximately 70% of multiple epiphyseal dysplasia (MED) cases. The genetic changes involved in the etiology of the remaining cases are still unknown, suggesting that other genes contribute to MED development. Our goal was to identify a mutation causing an autosomal dominant form of MED in a large multigenerational family. Initially, we excluded all genes known to be associated with autosomal dominant MED by using microsatellite and SNP markers. Follow‐up with whole‐exome sequencing analysis revealed a mutation c.2032G>A (p.Gly678Arg) in the COL2A1 gene (NCBI Reference Sequence: NM_001844.4), which co‐segregated with the disease phenotype in this family, manifested by severe hip dysplasia and osteoarthritis. One of the affected family members had a double‐layered patella, which is frequently seen in patients with autosomal recessive MED caused by DTDST mutations and sporadically in the dominant form of MED caused by COL9A2 defect.     

Primary adrenocortical nodular dysplasia with Cusghing's syndrome and cardiac myxomas

Summary In a family with 4 children, 2 had slowly developing Cushing's syndrome and were adrenalectomized between the ages of 18 and 28 years. As in other cases with familial Cushing's syndrome, primary adrenocortical nodular dysplasia, the so-called adrenocortical adenomatosis, was demonstrated. The brother, now 39 years old, is in good health. The sister, however, died at the age of 36 years. Autopsy revealed a cardiac myxoma of the left atrium. A cardiac myxoma had been found incidentally at autopsy of these two patients' oldest brother, a boy who died at the age of 4 years. Both siblings with Cushing's syndrome presented additional Peutz-Jegher-like hyperpigmentation and myxomatous tumours of the skin. Identical observations of familial adrenocortical nodular dysplasia, Cushing's syndrome and cardiac myxomas have not been reported to date. However, the familial occurrence of cardiac myxomas and adrenocortical dysplasia in combination with bilateral large cell calcifying Sertoli cell tumours of the testis has been published recently.     

Heritable dentin defects: Nosology,pathology, and treatment

Heritable dentin defects have been divided into 2 main categories: dentinogenesis imperfecta (DI) and dentin dysplasia (DD). Recent studies have shown that they share many features in common. Of the connective tissue diseases, only osteogenesis imperfecta (OI) has been linked to these disorders. So far, no definitive relation between the type of OI and the dental involvement can be established. Familial occurrence of DI with OI cannot be comprehensively explained by mutations in type I collagen genes. No information about the gene defects in DD is available. At the ultrastructural level, the organization of the normally cross-striated collagen fibers in the dentin matrix varies markedly in patients affected by DI.     

Hyperplastic foci in chronic liver disease: Their proliferative activity assessed by nucleolar organizing region

In the cirrhotic and precirrhotic liver, there may be small foci with increased cellularity and amphophilic cytoplasm. These are microscopic lesions that do not form macroscopically detectable nodules, which differ from the macroscopically apparent nodules of dysplastic nodules. In the present study, we assessed the proliferating activity of 12 hyperplastic foci in 11 patients with cirrhosis or chronic hepatitis, by staining for agyrophilic nucleolar organizing regions (AgNOR). The mean AgNOR count per nucleus in the hyperplastic foci ranged from 0.96 to 1.36 (mean, 1.13; SD 0.12), and from 0.81 to 1.06 (mean, 0.94; SD 0.08) in the controls. The AgNOR count In the hyperplastic foci was significantly higher than that In the controls (P> 30.01). Small hyperplastic foci show Increased proliferative activity. Further study on these foci is required to clarify their relation to hepatocarcinogenesis.