Jotaro Hata

Alpha1-antitrypsin, alpha1-antichymotrypsin, and alpha2-macroglobulin in human gastric carcinomas: A retrospective immunohistochemical study

One hundred twenty-six gastric carcinomas (68 advanced cancers and 58 early cancers) were examined immunohistochemically for alpha 1-antitrypsin (AAT), alpha 1-antichymotrypsin (ACT), and alpha 2-macroglobulin (AMG) within tumor cells. The incidence of these three protease inhibitors was markedly higher in advanced than in early cancers, regardless of the histologic type of gastric carcinoma. In advanced cancers the incidence of both AAT and AMG was significantly higher in well-differentiated adenocarcinomas than in poorly differentiated adenocarcinomas, but no difference was observed in the expression of ACT between these two types of advanced carcinomas. Eighty per cent of the AAT-positive advanced carcinomas had ACT, and 40 per cent of these tumors also contained AMG. The two-year survival rates clearly indicated that well-differentiated adenocarcinomas with AAT have worse prognoses than well-differentiated adenocarcinomas without AAT, but there was no relation between the expression of ACT or AMG and prognosis. These results strongly suggest that the presence of protease inhibitors in gastric carcinomas is related to the invasive growth of the tumors and that AAT is a tissue tumor marker of well-differentiated adenocarcinomas of the stomach. It may also serve as a biologic marker of high malignancy in patients with these gastric cancers.

Tubular adenoma of the human stomach. An immunohistochemical analysis of gut hormones, serotonin, carcinoembryonic antigen, secretory component, and lysozyme.

A total of 49 gastric tubular adenomas and 6 tubular adenomas with foci of adenocarcinoma from surgically resected stomachs were examined histologically and immunohistochemically for gut peptide hormones, serotonin, Carcinoembryonic antigen (CEA), secretory component (SC), and lysozyme. A variety of endocrine cells were detected in tubular adenoma with mild to moderate atypia. Both the frequency and distribution density were highest for serotonin‐containing EC cells, often showing hyperplasia, followed by glicentin‐containing L cells, somatostatin‐containing D cells and motilin‐containing Mo cells in the order given. Adenoma cells with SC immunoreactivity were more dominant than those with CEA immunoreactivity. In tubular adenoma with severe atypia, endocrine cells were markedly decreased, whereas adenoma cells with CEA immunoreactivity were increased. The distribution density of lysozyme‐containing cells in tubular adenoma of the intermediate zone and fundus was significantly higher than that of the antrum. In the subjacent mucosa of the adenoma, L cells and SC‐positive epithelial cells were detected in 24 and 33 cases, respectively. These findings suggest that gastric tubular adenoma develops from intestinal metaplasia. In addition, gastric tubular adenoma showed a tendency to lose various intestinal markers with increase of histologic atypicality.

Glicentin-containing cells in intestinal metaplasia, adenoma and carcinoma of the stomach

Glicentin-containing cells (Glic. cells) in intestinal metaplasia, adenoma and carcinoma of the stomach were examined using immunohistochemical techniques. Glic. cells first occurred in the gastric mucosa of the transitional area between metaplastic and intact gastric glands. They frequently showed hyperplasia or micronoduli in the budding area of the deeper metaplastic glands, but in completely intestinalized mucosa these endocrine cells decreased remarkably. Gastric adenomas with mild dysplasia had a good number of glicentin-immunoreactive cells which were located in the deeper adenoma glands. Gastrin- and somatostatin-positive cells were also detected in the adenomas. The incidence of glicentin-positive tumor cells was significantly higher in well differentiated adenocarcinoma than in poorly differentiated adenocarcinoma. Among the seven cases of scirrhous argyrophil cell carcinoma, three showed glicentin- and glucagon-immunoreactivity in the same area of the tumor. These findings suggest that the selective increase of Glic. cells in intestinal metaplasia may be closely related to the development of gastric adenoma. Glicentin positive tumor cells in gastric carcinomas can be regarded to be an expression of intestinal or fetal markers.

Gut endocrine cells in rat stomach carcinoma induced by N-methyl-N'-nitro-N-nitrosoguanidine.

SummaryGut endocrine cells in a total of 18 gastric adenocarcinomas in inbred Wistar rats induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) and gastrin or serotonin, were examined histologically, ultrastructurally, and immunohistochemically for gastrin, somatostatin, calcitonin, glicentin, and serotonin. A large number of argyrophil cells were observed in 17 tumors (94.4%) and 14 tumors (77.8%) had argentaffin cells. Immunohistochemically, C-terminal fragment of gastrin (G17) immunoreactivity was observed in 15 (82.2%) out of the 18 tumors, but 3 G17-positive tumors had no G 34 immunoreactive cells in rats treated with MNNG plus gastrin. Serotonin immunoreactivity was detected in 14 tumors (77.8%). Somatostatin immunoreactivity was detected in 7 of the 11 tumors (63.6%) in rats treated with MNNG plus gastrin whereas no tumor in rats treated with MNNG plus serotonin had somatostatin, the difference of the incidence being significant (P<0.05). One endocrine cell carcinoma which consisted mainly of serotonin-producing cells was observed in a rat treated with MNNG plus serotonin. Calcitonin and glicentin immunoreactivity was not demonstrated in any tumors. Ultrastructurally, three types of endocrine granule were found in the tumor cells.These data suggest that hormonal environment in stomach carcinogenesis may influence the expression of endocrine cells within the tumors.

Calcitonin in human gastric mucosa and carcinoma

SummaryThe localization of immunoreactive calcitonin (IR-CT) in the human gastric mucosa and tumor tissues was studied using an immunohistochemical peroxidase-antiperoxidase method. A small number of IR-CT-containing cells were observed in both infant and adult gastric antral mucosa and the ratio of IR-CT-containing cells to G cells was about 1:50-100. Moreover, tissue content of IR-CT in normal antral mucosa was 2.37±0.35 ng/g wet weight. IR-CT-containing cells and G cells decreased with the progress of chronic atrophic gastritis and were totally absent in intestinal metaplastic glands. IR-CT was detected in G cells, suggesting a paracrine relation between gastrin and CT. IR-CT was not found in tumor cells of 35 gastric adenomas and 40 well differentiated adenocarcinomas. On the other hand, it was demonstrated in a very small number of tumor cells in 4 of 46 poorly differentiated adenocarcinomas, and in a good number in 3 of 7 scirrhous argyrophil cell carcinomas. IR-CT in plasma could serve, therefore, as a tumor marker of scirrhous endocrine cell carcinoma, and its production in cancer cells was considered to be eutopic rather than ectopic.

Serotonin in tubular adenomas, adenocarcinomas and endocrine tumours of the stomach. An immunohistochemical study.

Serotonin was examined immunohistochemically in seven tubular adenomas, 194 adenocarcinomas and 41 endocrine cell tumours of the stomach. In tubular adenomas, serotonin-containing cells showing argentaffinity were present in the lower portion of the adenomatous glands and were considered to be an expression of intestinal character. Scattered serotonin-containing tumour cells were found in 60 (30.9%) of 194 adenocarcinomas regardless of their histological type. Cell fusions between carcinoma and enterochromaffin (EC) cells might be a possible mechanism for the occurrence of serotonin-containing cells within the tumour. In 17 (54.8%) of 31 endocrine cell carcinomas, serotonin-containing tumour cells were observed in a variable degree in contrast to the absence of these cells in classical carcinoid. Moreover, diffuse serotonin reactivity was found in four cases of scirrhous endocrine cell carcinoma. The histogenesis and the occurrence of serotonin-containing cells in each type of gastric tumour is also discussed.