The two histological main types of gastric carcinoma; diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification

Pathology and genetics of tumors of soft tissue and bone

A model for gastric cancer epidemiology.

The calcium-dependent homophilic cell adhesion molecule and candidate suppressor gene, E (epithelial)-cadherin, plays a major role in the organization and integrity of most epithelial tissues Diffusely growing gastric carcinomas show markedly reduced homophilic cell-to-cell interactions We speculated that mutations in the E-cadherin gene may be responsible for the scattered phenotype of this type of carcinoma For that reason we have examined E-cadherin in 26 diffuse type, 20 intestinal type and 7 mixed gastric carcinomas (Lauren9s classification) at the DNA, RNA, and protein levels Reverse transcription polymerase chain reaction and direct sequencing of amplified E-cadherin complementary DNA fragments revealed inframe skipping of either exon 8 or exon 9 in 10 patients with diffuse tumors and an exon 9 deletion in one patient with a mixed carcinoma; both exons encode putative calcium binding domains These alterations were not seen in nontumorous gastric tissues Splice site mutations responsible for the exon deletions were identified in six of these patients, eliminating the possibility of alternative splicing mechanisms Five of these splice site alterations were confirmed as somatic mutations Non-splice site mutations were observed in three diffuse type tumors, namely a 69-base pair deletion of exon 10 and two point mutations, one of which destroys a putative calcium binding region Immunohistochemical evaluation showed E-cadherin immunoreactivity in tumors and lymph node metastases of patients expressing abnormal mRNA The allelic status of the E-cadherin gene was analyzed in one patient, revealing loss of heterozygosity with retention of a mutated E-cadherin allele Overall, E-cadherin mutations were identified in 50% (13 of 26) of the diffuse type and in 14% (1 of 7) of the mixed carcinomas In contrast, two silent E-cadherin mutations (not changing the amino acid sequence) were detected in two tumors of the intestinal type Our study provides strong in vivo evidence that E-cadherin gene mutations may contribute to the development of diffusely growing gastric carcinomas and support a tumor/metastasis suppressor gene hypothesis

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E-cadherin gene mutations provide clues to diffuse type gastric carcinomas.

Carcinogenesis of Helicobacter pylori

Summary PLO-SL (polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy) is a recessively inherited disorder characterized by systemic bone cysts and progressive presenile frontal-lobe dementia, resulting in death at

Assignment of the Locus for PLO-SL, a Frontal-Lobe Dementia with Bone Cysts, to 19q13

Intracellular cysts were often found in the tumour cells in gastric carcinomas of intestinal as well as diffuse type in specimens from stomachs resected for gastric cancer. In the light microscope, the cysts appeared usually as solitary cytoplasmic vacuoles. In the electron microscope, the intracellular cysts were seen as round cavities, often containing homogenous or granular mucous material which stained with the periodic acid-silver methenamine (PASM)-method. Relatively long microvilli were lining the cysts and, not infrequently, abundant cytoplasmic microfilaments would surround the cyst wall. Similar cysts have been observed in a number of other tumours and, accordingly, their diagnostic significance must be considered in connection with other methods such as differential staining of cellular mucosubstances.

Intracellular cysts in gastric carcinoma.

Extraskeletal retroperitoneal osteosarcoma probably arising from myositis ossificans

(1945). Heterotopic tumors with an intestinal mucous membrane structure in the nasal cavity. Acta Oto-Laryngologica: Vol. 33, No. 6, pp. 471-485.

Heterotopic tumors with an intestinal mucous membrane structure in the nasal cavity.

More than 50 cases of polycystic lipomembranous osteodysplasia (PLO) with sclerosing leukoencephalopathy (SL) have been described in Finland, Sweden Japan, and in the USA. Radiographic bone changes, including symmetrical cystic lesions in the small bones of the extremities and trabecular loss in the distal ends of the long tubular bones, represent primary abnormalities in the diagnosis of the disease. Neuropsychiatric symptoms, frontal syndrome, and pyramidal signs make the patients dangerous to themselves. They are often involved in traffic accidents and are prone to multiple spontaneous or almost spontaneous fractures. PLO usually starts with slight bone pain around the age of 20 years. Progress is very slow during the next ten years, but faster after the age of 40 years. The patients usually die before the age of 50 years having total dementia and epileptiform convulsions.

Osmo H. Järvi

Papers

Assignment of the Locus for PLO-SL, a Frontal-Lobe Dementia with Bone Cysts, to 19q13

Intracellular cysts in gastric carcinoma.

Extraskeletal retroperitoneal osteosarcoma probably arising from myositis ossificans

Heterotopic tumors with an intestinal mucous membrane structure in the nasal cavity.

Radiologic bone changes of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy.