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

On the role of heterotopias of the intestinal epithelium in the pathogenesis of gastric cancer

In a series of 235 autopsies, changes in the subcapscular thoracic fascia similar to elastofibroma dorsi (Jarvi & Saxen 1959, -et al. 1969) were found in 39 cases, all at least 58 years old. In people over 55 years, the frequency was 24.4 per cent in females and 11.2 per cent in males. In addition to hypertrophy and secondary degeneration of elastic fibres, necrosis of collagenous-, adipose-, muscular-, and nervous tissue, as well as formation of clefts, cysts and bursae was found in 85 per cent of cases presenting elastic changes--both in connection with them and outside the degenerated areas--as well as in 39 per cent of cases where no elastic degeneration occurred. Other changes included extensive scarring of the tissue, followed by reduction of fat and, more seldom, oedema and inflammatory infiltration. Breaks in the elastic cage, necrosis and fibrosis of arterial walls were found in 44 per cent of cases of elastic degeneration and in 14 per cent of cases without degeneration. In veins, more extensive wall fibrosis occurred, leading to necrosis; in cases of elastic degeneration the adventitial elastic network was also involved. Venous changes were found in 90 per cent of the cases of elastic degeneration and in 30 per cent of cases without degeneration. Direct mechanical stress on elastic tissue may be an important cause of hypertrophy and secondary degeneration of elastic fibres, and also of diffuse increase of collagenous tissue. On the other hand, nutritional deficiency due to failing resistance of the vascular system against friction of the scapula and streching movements of the upper extremities may play a main part in necrotic tissue changes.

Subclinical elastofibromas in the scapular region in an autopsy series.

In view of uncertainty regarding the criteria and significance of gastric dysplasia as a precancerous lesion, members of the Pathology Panel of the International Study Group on Gastric Cancer (ISGGC) reviewed microslides of 93 gastric lesions showing varying degrees of mucosal abnormality, and reached the following consensus: (1) immature and proliferating gastric epithelium can be divided into two categories: hyperplastic and dysplastic; (2) the term dysplasia, especially of high-grade type, should be restricted to precancerous lesions, and hyperplasia is applied to regenerative changes; (3) regenerative hyperplasia may be simple or atypical, but dysplasia includes both moderate and severe abnormalities, since they often coexist and can not be sharply separated; and (4) occasionally the possibility of malignancy can not be excluded in a severely dysplastic epithelium; in such a case rebiopsy and diligent follow-up are necessary to establish the diagnosis. Criteria for diagnosing dysplasia and hyperplasia are presented and discussed. The opinions are offered as guidelines for establishing the diagnosis of gastric dysplasia and for prospective studies.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819841101%2954%3A9%3C1794%3A%3AAID-CNCR2820540907%3E3.0.CO%3B2-W

Gastric dysplasia. Significance and pathologic criteria

On the cellular structures of the epithelial invasions in the glandular stomach of mice caused by intramural application of 20-methylcholantren.

Samples from 56 resected stomachs, including 28 cases of intestinal and 14 of diffuse type gastric carcinoma, were studied by electron microscopy. The main ultrastructural features of intestinal and diffuse type gastric carcinomas were described and compared to the ultrastructure of normal gastric mucosal cells and cells occurring in intestinal metaplasia of the gastric mucosa. Many similarities were demonstrated between intestinal metaplasia and intestinal type carcinomas. The cells of diffuse type carcinomas closely resembled the goblet cells of intestinal metaplasia. Microvilli, similar to those in the brush border of the intestinal columnar cells, could be demonstrated in the carcinomatous surface epithelium and occasionally also in individually spreading cells of the diffuse type carcinoma. Intracellular cysts with microvilli on the cyst wall were occasionally found in both types of carcinoma. The histogenetic origin of gastric carcinoma was discussed.

Osmo H. Järvi

Papers

On the role of heterotopias of the intestinal epithelium in the pathogenesis of gastric cancer

Subclinical elastofibromas in the scapular region in an autopsy series.

Gastric dysplasia. Significance and pathologic criteria

On the cellular structures of the epithelial invasions in the glandular stomach of mice caused by intramural application of 20-methylcholantren.

Ultrastructure of intestinal and diffuse type gastric carcinoma