Scirrhous carcinoma of the stomach: a clinical and pathological study of 106 surgical cases

Clinical and pathological characteristics of scirrhous carcinoma of the stomach were studied in 106 cases treated by gastrectomy between 1973 and 1983. The male to female ratio was 0.58. The percentage of scirrhous carcinomas to all gastric carcinomas resected in the same period was three times higher in females than males. The age distribution of the patients suggested that there were two peaks in the forties and sixties in the male, and in the thirties and fifties in the female. The incidence of scirrhous carcinoma in all types of gastric carcinoma was significantly higher in the twenties, thirties and forties compared to the lowest incidence in the seventies. In the female group the primary lesion had a tendency to be adjacent to the fundic gland area and to avoid intestinal metaplasia. In the male the opposite was recognized. Cancer nests with single cells or only several cells were common in this type of carcinoma. These findings suggest that there might be two biologically different scirrhous carcinomas both in the male and the female, the appearance of single carcinoma cells might be favored by female sex hormones and young ages, and not only the original gastric mucosa but also mucosa with intestinal metaplasia could be precursors of single carcinoma cells.     

Expression of MUC2 in gastric carcinomas and background mucosae

BACKGROUND AND AIM: Gastric carcinomas contain elements of both intestinal and diffuse types. Such heterogeneous components may distort the evaluation of the role of the mucin MUC2 in gastric carcinoma. The role of MUC2 expression in background mucosa is not yet clarified. METHODS: We analyzed the expression of MUC2 in gastric mucosa and intestinal metaplasia adjacent to the tumoral area and carcinomas (n = 98) using immunohistochemistry. The immunoreactivity was quantified using an immunohistochemical scoring system. RESULTS: In the intestinal metaplasia adjacent to the tumoral area, MUC2 was detected in 76 (97.4%) of 78 intestinal metaplasia, and MUC2 expression was inversely associated with the depth of wall penetration (P = 0.026) and tumor stage (P = 0.021). Although the expression rate of MUC2 antigens was higher in intestinal-type adenocarcinoma than in diffuse-type adenocarcinoma, a significant correlation with pathologic staging of the TNM system (pTNM staging) and MUC2 expression could not be found in each subtype of gastric carcinomas. CONCLUSION: The expression of MUC2 in intestinal metaplasia was higher in tumors of earlier stages. These findings suggest that increased MUC2 expression in intestinal metaplasia in the neighborhood of the carcinomas may play an important role in gastric carcinomas. Further investigations regarding the role of MUC2 expression in gastric carcinoma and background mucosae are necessary.     

The intestinal and diffuse type of the gastric carcinoma (author's transl)

According to the Laurén classification 357 carcinomas of the stomach were reclassified into intestinal and diffuse types. 58.2% were assigned to the intestinal type, 37.5% to the diffuse and 4% to a "mixed" group. There is obvious correlation between the intestinal type, the patients' advancing age and the incidence of chronic, atrophising gastritis with intestinal metaplasia. The diffuse type on the other hand occurs irrespective of gastric changes - mostly in younger persons. The intestinal type of gastric carcinoma frequently is found in risk areas where incidence is "epidemic" in nature; morphology and genetic origin seem to be gastric mucosa changes and intestinal metaplasia or dysplasia. Classifying gastric carcinoma according to Laurén (two groups) is also an appropriate method in our regions as was confirmed by the results we obtained; it is superior to the much more differentiated macro- and microscopic classifications used so far. Because of its simplicity, it is better suited for epidemiological and pathogenetic studies of the gastric carcinoma.     

胃癌及其癌前病变中细胞凋亡与细胞增殖间关系的研究

目的　通过观察胃癌及其癌前病变中细胞凋亡与细胞增殖间的关系,探讨细胞凋亡在胃癌发生中的作用．方法　利用脱氧核糖核酸末端转移酶介导的ｄ ＵＴＰ 缺口末端标记（ＴＵＮＥＬ） 技术及增殖细胞核抗原（ ＰＣＮＡ） 免疫组织化学染色对１０ 例正常胃粘膜、１６ 例萎缩性胃炎、３６ 例肠化生、２０ 例异型增生和５３ 例胃癌中的凋亡细胞、增殖细胞进行原位观察和比较．结果　萎缩性胃炎、肠化生、异型增生中凋亡细胞指数（１１－９ ％ ;１４－７ ％ ,８－０ ％ ） 均显著高于正常胃粘膜和 胃癌（３－５ ％ ,５－８ ％ ,ｔ ＝ ２－０５８ ～７－９０１ ,Ｐ＜ ０－０１ ～Ｐ ＜ ０－０５） ;异型增生、胃癌与肠化生相比,凋亡细胞明显减少、增殖细胞明显增多（ Ｐ＜ ０－０５） ;胃癌细胞增殖指数（４７－５ ％ ） 显著高于异型增生（３０－１ ％ ,Ｐ＜ ０－０１） ． 胃癌前病变及胃癌组织中的凋亡细胞指数与 增 殖细 胞指 数 呈显 著相 关（ ｒ ＝ ０－９６６ , － ０－８９７ ,Ｐ＜ ０－０５） ．结论　胃粘膜癌变过程中不仅存在活跃的细胞增殖,而且存在细胞凋亡异常． 高增殖能力的细胞可能通过选择而占据优势,导致胃癌的发生． 细胞凋亡与细胞增殖平衡失调在胃癌发病中可能起重要作用     

Atrophy-metaplasia-dysplasia-carcinoma sequence in the stomach: a reality or merely an hypothesis?

The results of recent investigations have suggested that the old hypothesis of an atrophy-metaplasia-dysplasia-carcinoma sequence in the stomach needs to be qualified. The most common cause of intestinal metaplasia is Helicobacter pylori gastritis. The consequence of this intestinal metaplasia is focal atrophy. Helicobacter pylori infection may also trigger an autoimmune gastritis of the corpus mucosa, with atrophy and intestinal metaplasia. Most intestinal metaplasias are only 'paracancerous' but not 'precancerous' lesions. Diffuse gastric carcinomas, such as the signet ring cell carcinoma, arise independently of intestinal metaplasia. Histogenetically, numerous carcinomas of the stomach are primarily of the gastric type, and may secondarily change into the intestinal type.High-grade intra-epithelial neoplasias (dysplasias) detected during the biopsy-based diagnostic work-up appear to be a marker for carcinoma and must, therefore, be removed endoscopically.The detection of intestinal metaplasia in routinely obtained biopsy material is subject to sampling error and is, therefore, not a suitable marker for an increased risk of a gastric carcinoma developing. As an alternative, the concept of gastritis of the carcinoma phenotype, which is more frequently found in early gastric carcinomas and in the relatives of gastric carcinoma patients, has been developed. In this concept, the diffuse parameters of grade and activity of the gastritis in the antrum and corpus, which are independent of sampling error, are subjected to a comparative analysis. A risk gastritis of the carcinoma phenotype is diagnosed when the grade and activity of the gastritis in the corpus are at least equally as pronounced as in the antrum. Currently, this concept is being tested in a prospective ongoing study. Future studies must show whether, and if so which, immunohistochemical or molecular-genetically detectable changes can be applied as risk markers in the diagnostic work-up. Helicobacter pylori eradication probably does not lead to complete regression of the intestinal metaplasia and ensuing focal atrophy. However, eradication of H. pylori does lead to the normalization of changes that can lead to mutations of the stem cells of the gastric mucosa (free radicals, nitric oxide, cell proliferation and vitamin C secretion).     

Epstein-Barr virus-associated gastric carcinoma and atrophic gastritis.

Although Epstein-Barr virus (EBV) has been reported to be present in some 7% of gastric carcinomas, the nature of the background gastric mucosa of carcinoma has not been elucidated. The authors evaluated the degree of gastritis in the background gastric mucosa of EBV-associated gastric carcinoma. EBV was detected using in situ hybridization for EBV-encoded small ribonucleic acid 1 (EBER-1) in carcinoma cells. The authors compared gastritis in surgically resected stomachs with 8 EBER-1-positive and 16 EBER-1-negative gastric carcinomas of a similar histologic type using histologic variables of the Updated Sydney System. All eight lesions of EBER-1-positive gastric carcinomas had intestinal metaplasia in the background. Mild to moderate glandular atrophy was common in both groups. Many of the tested lesions, 87.5% of EBER-1-positive and 62.5% of EBER-1-negative lesions, were located near the mucosal atrophic border. The background gastric mucosa for EBV-associated gastric carcinomas is rich in atrophic changes. EBV-associated gastric carcinomas are located near the mucosal atrophic border.     

Gastric carcinoma in young Hong Kong Chinese

Gastric carcinomas usually occur in older people. Those occurring in the young are uncommon. The pathological and clinical features of gastric carcinomas were reviewed in 42 Chinese patients who were 35 years of age and younger. The data were obtained from the record files of the University Department of Pathology, Queen Mary Hospital for the period 1976-85. The patients comprised 4% of the total cases of gastric carcinomas in that period. These patients (age range: 20-35 years, mean: 30 years) showed a male to female ratio of 1:2.5 which differs from the usual male preponderance seen in gastric carcinoma. Among the 27 cases with known staging, 22 (81.5%) were stage III or IV. Twenty-five cases had an ulcerative appearance. All were adenocarcinomas and the majority (83.3%) were poorly differentiated. Associated dysplasia was found in 35 (83.3%) cases, although only 14 of these were in association with poorly differentiated adenocarcinomas. Intestinal metaplasia was found in 13 cases and, when present, involved less than 30% of the mucosa. Only two cases were of type III metaplasia. The findings show that gastric carcinoma in young Chinese tended to occur more frequently in females, presented at late stages, showed poor glandular differentiation, was frequently associated with gastric dysplasia and had minimal association with intestinal metaplasia.     

Calcitonin in human gastric mucosa and carcinoma

Summary The 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.Supported in part by Grant-in Aid for Cancer Research from the Ministry of Education, Science and Culture (No. 59010074).     

Atrophy–metaplasia–dysplasia–carcinoma sequence in the stomach: a reality or merely an hypothesis?

The results of recent investigations have suggested that the old hypothesis of an atrophy–metaplasia–dysplasia–carcinoma sequence in the stomach needs to be qualified. The most common cause of intestinal metaplasia is Helicobacter pylori gastritis. The consequence of this intestinal metaplasia is focal atrophy.Helicobacter pylori infection may also trigger an autoimmune gastritis of the corpus mucosa, with atrophy and intestinal metaplasia. Most intestinal metaplasias are only ‘paracancerous’ but not ‘precancerous’ lesions. Diffuse gastric carcinomas, such as the signet ring cell carcinoma, arise independently of intestinal metaplasia. Histogenetically, numerous carcinomas of the stomach are primarily of the gastric type, and may secondarily change into the intestinal type.High-grade intra-epithelial neoplasias (dysplasias) detected during the biopsy-based diagnostic work-up appear to be a marker for carcinoma and must, therefore, be removed endoscopically.The detection of intestinal metaplasia in routinely obtained biopsy material is subject to sampling error and is, therefore, not a suitable marker for an increased risk of a gastric carcinoma developing. As an alternative, the concept of gastritis of the carcinoma phenotype, which is more frequently found in early gastric carcinomas and in the relatives of gastric carcinoma patients, has been developed. In this concept, the diffuse parameters of grade and activity of the gastritis in the antrum and corpus, which are independent of sampling error, are subjected to a comparative analysis. A risk gastritis of the carcinoma phenotype is diagnosed when the grade and activity of the gastritis in the corpus are at least equally as pronounced as in the antrum. Currently, this concept is being tested in a prospective ongoing study. Future studies must show whether, and if so which, immunohistochemical or molecular-genetically detectable changes can be applied as risk markers in the diagnostic work-up.Helicobacter pylori eradication probably does not lead to complete regression of the intestinal metaplasia and ensuing focal atrophy. However, eradication ofH. pylori does lead to the normalization of changes that can lead to mutations of the stem cells of the gastric mucosa (free radicals, nitric oxide, cell proliferation and vitamin C secretion).     

Endoscopic diagnosis of intestinal metaplasia in asymptomatic (control) volunteers.

The F-P border and strain phenomenon of the gastric mucosa were investigated by the application of methylene blue dye spraying method in endoscopy to 105 asymptomatic control volunteers and the following results were obtained; 1. The pyloric metaplasia is observed in the fundic gland area from the twenties in age and becomes increasing in its number and move widely spreading from the lesser curvature to the anterior and/or posterior wall of the corpus with advancing age. 2. The intestinal metaplasia arises from the thirties in age. 3. The intestinal metaplasia is observed either in the pyloric gland area of following the pyloric metaplasis in the fundic gland area. 4. Histologically, the strain phenomenon of the gastric mucosa is closely related to the intestinal metaplasia. Then, methylene blue dye spraying method is reevaluated to be useful for a precise endoscopic diagnosis of intestinal metaplasia.     

Helicobacter pylori infection and expression of the angiogenic factor platelet-derived endothelial cell growth factor by pre-neoplastic gastric mucosal lesions and gastric carcinoma

BACKGROUND: Expression of the angiogenic factor platelet-derived endothelial cell growth factor is induced in some gastric carcinomas. Whether angiogenesis is induced early in the development of gastric pre-neoplastic lesions and whether Helicobacter pylori infection affects platelet-derived endothelial cell growth factor expression is not known. AIM: To assess whether chronic gastritis, intestinal metaplasia, gastric dysplasia and gastric carcinomas express platelet-derived endothelial cell growth factor and whether Helicobacter pylori infection might affect the expression of platelet-derived endothelial cell growth factor in these lesions. PATIENTS AND METHODS: Patients with gastric carcinomas, atrophic gastritis with associated intestinal metaplasia, dysplasia and controls without infection or carcinoma were studied. RESULTS: Platelet-derived endothelial cell growth factor was detected by immunohistochemistry in 9 out 19 gastric carcinomas (45%). Only focal immunostaining was detected in intestinal metaplasia adjacent to dysplasia and in dysplastic cells. Of the tumours, 90% contained platelet-derived endothelial cell growth factor-positive interstitial cells. A significant correlation was found between active Helicobacter pylori infection and a larger number of platelet-derived endothelial cell growth factor-positive interstitial cells in areas of intestinal metaplasia (p<0.05). CCONCLUSION:Helicobacter pylori infection does not influence the expression of platelet-derived endothelial cell growth factor, once gastric cancer has developed. However, Helicobacter pylori infection may increase the extension of expression of platelet-derived endothelial cell growth factor by infiltrating interstitial cells in premalignant lesions, such as intestinal metaplasia, which may help create a favourable environment for tumour development. This may possibly be due to non-specific increase in recruitment of inflammatory cells caused by Helicobacter pylori infection. Further studies, with a larger number of samples, are now needed in order to confirm this finding.     

Differences in proximal （cardia） versus distal （antral） gastric carcinogenesis via retinoblastoma pathway

AIM: Disruption of cell cycle regulation is a critical event in carcinogenesis, and alteration of the retinoblastoma (pRb) tumour suppressor pathway is frequent. The aim of this study was to compare alterations in this pathway in proximal and distal gastric carcinogenesis in an effort to explain the observed striking epidemiological differences. METHODS: Immunohistochemistry was performed to investigate expression of p16 and pRb in the following groups of both proximal (cardia) and distal (antral) tissue samples: (a) biopsies showing normal mucosa, (b) biopsies showing intestinal metaplasia and, (c) gastric cancer resection specimens including uninvolved mucosa and tumour. RESULTS: In the antrum there were highly significant trends for increased p16 expression with concomitant (and in the group of carcinomas inversely proportional) decreased pRb expression from normal mucosa to intestinal metaplasia to uninvolved mucosa (from cancer resections) to carcinoma. In the cardia, there were no differences in p16 expression between the various types of tissue samples whereas pRb expression was higher in normal mucosa compared with intestinal metaplasia and tissue from cancer resections. CONCLUSION: Alterations in the pRb pathway appear to play a more significant role in distal gastric carcinogenesis. It may be an early event in the former location since the trend towards p16 overexpression with concomitant pRb underexpression was seen as early as between normal mucosa and intestinal metaplasia. Importantly, the marked differences in expression of pRb and p16 between the cardia and antrum strongly support the hypothesis that tumours of the two locations are genetically different which may account for some of the observed epidemiological differences.     

Differences in proximal (cardia) versus distal (antral) gastric carcinogenesis via retinoblastoma pathway

AIM: Disruption of cell cycle regulation is a critical event in carcinogenesis, and alteration of the retinoblastoma (pRb)tumour suppressor pathway is frequent. The aim of this study was to compare alterations in this pathway in proximal and distal gastric carcinogenesis in an effort to explain the observed striking epidemiological differences.METHODS: Immunohistochemistry was performed to investigate expression of p16 and pRb in the following groups of both proximal (cardia) and distal (antral) tissue samples: (a) biopsies showing normal mucosa, (b) biopsies showing intestinal metaplasia and, (c) gastric cancer resection specimens including uninvolved mucosa and tumour.RESULTS: In the antrum there were highly significant trends for increased p16 expression with concomitant (and in the group of carcinomas inversely proportional)decreased pRb expression from normal mucosa to intestinal metaplasia to uninvolved mucosa (from cancer resections)to carcinoma. In the cardia, there were no differences in p16 expression between the various types of tissue samples whereas pRb expression was higher in normal mucosa compared with intestinal metaplasia and tissue from cancer resections.CONCLUSION: Alterations in the pRb pathway appear to play a more significant role in distal gastric carcinogenesis.Tt may be an early event in the former location since the trend towards p16 overexpression with concomitant pRb underexpression was seen as early as between normal mucosa and intestinal metaplasia. Importantly, the marked differences in expression of pRb and p16 between the cardia and antrum strongly support the hypothesis that tumours of the two locations are genetically different which may account for some of the observed epidemiological differences.     

Hypergastrinaemia induced by partial corpectomy results in development of enterochromaffin-like cell carcinoma in male Japanese cotton rats

BACKGROUND: Among inbred female cotton rats (Sigmodon hispidus) 25%-50% of the animals develop spontaneous gastric carcinomas, whereas males have an incidence of less than 1%. The carcinomas are enterochromaffin-like (ECL)-cell derived. Animals with gastric carcinomas also have hypergastrinaemia and gastric hypoacidity, but the mechanism behind the hypoacidity is unknown. Carcinomas have been found in all female cotton rats with spontaneous hypergastrinaemia lasting more than 4 months, and a gastrin receptor antagonist prevents the development of carcinoma. The purpose of the present study was to investigate whether induced hypergastrinaemia in male cotton rats would also result in carcinomas. METHODS: Hypergastrinaemia was induced by partial corpectomy of male cotton rats, aiming at removal of 80%-90% of the corpus. A control group was sham-operated. RESULTS: All partially corpectomized animals developed persistent hypergastrinaemia. Six months after the operation, 9 out of 13 partially corpectomized animals developed gastric cancer. In the dysplastic mucosa surrounding the tumours there was an increase in chromogranin A immunoreactive cells, where numerous cells also were stained using the Sevier-Munger technique. Tumour tissue also contained cells that were chromogranin A positive and stained by Sevier-Munger. CONCLUSIONS: ECL-cell carcinomas can be induced in male cotton rats by partial corpectomy. This supports a previous statement that spontaneous carcinomas in female cotton rats are caused by gastric hypoacidity and hypergastrinaemia. In hypergastrinaemic animals, ECL-cell carcinomas develop independently of gender within a relatively short period of time, and cotton rats therefore represent an interesting model for studying gastric carcinogenesis.     

幽门螺杆菌及胃粘膜肠上皮化生与CD_(44)V_6表达的关系

目的　探讨幽门螺杆菌 (Hp)感染及慢性萎缩性胃窦炎伴肠上皮化生与CD4 4V6表达程度之间的关系。方法　以单克隆抗体及免疫组化技术等方法对Hp阴性单纯慢性胃炎、Hp阴性萎缩性胃炎伴肠上皮化生、Hp阳性萎缩性胃窦炎伴肠上皮化生、胃窦腺癌的胃镜下活检组织标本进行测定分析。结果　在Hp阴性单纯性胃炎组粘膜上皮未见CD4 4V6表达 ,Hp阴性萎缩性胃窦炎伴肠上皮化生、Hp阳性萎缩性胃窦炎伴肠上皮化生、胃窦腺癌各组CD4 4V6表达程度依次逐渐升高 ,各组之间比较差异有显著性 (P <0 .0 5 )。结论　CD4 4V6的表达可能是上皮细胞癌前病变出现的早期生物学信号 ,肠上皮化生细胞可能诱导CD4 4V6的表达 ,而Hp感染则有促进这种诱导表达的作用。     

Re-evaluation of Histogenesis of Gastric Carcinomas: A Comparative Histopathological Study Between Helicobacter pylori-Negative and H. pylori-Positive Cases

We histopathologically re-evaluated the histogenesis of gastric carcinomas from comparative studies between Helicobacter pylori-positive and H. pylori-negative cases using the gastritis score from the Updated Sydney System. The incidence of H. pylori-negative gastric carcinomas was 3.11% (12/386); they are likely to develop in the fundic gland mucosa, and show a gastric phenotype by mucin immunohistochemistry. Even in cases of completely gastric and predominantly gastric phenotypes, CDX2 protein was expressed in most cases (90.9% of pT1 and 100% of pT2-3), indicating a possibility that intestinalization of carcinoma cells occurs independently of the background mucosa. Regarding the degree of gastritis of background mucosa surrounding 143 H. pylori-positive differentiated-type adenocarcinomas, the mean score ranged from 1.497 to 1.713. Our data support the hypothesis that intestinal metaplasia is not a precancerous but a paracancerous lesion, and most gastric adenocarcinomas develop in mildly to moderately atrophic mucosa with H. pylori-infection, i.e., ongoing atrophy.     

Apoptotic cell death and its relationship to gastric carcinogenesis

AIM: To investigate the apoptotic process of cells with in the intestinal metaplasia areas co-localizing with chronic gastritis and gastric carcinomas and to analyze the involvement of proteins regulating apoptosis in the process of intestinal metaplasia related gastric carcinogenesis. METHODS: Forty-two gastric carcinoma and seventeen chronic gastritis cases were included in this study. All cases were examined for the existence of intestinal metaplasia. Ten cases randomly selected from each group were processed for TUNEL assay. TUNEL positive cells within the intestinal metaplasia areas, co-localizing either to gastric carcinoma or chronic gastritis, were counted and converted to apoptotic indices. In addition, p53, bcl-2 and bax expression patterns within these tissues were analyzed on the basis of immunohistochemistry. RESULTS: Twenty-eight of the cases were intestinal and 14 of the cases were diffuse type adenocarcinomas. 64% (27/42) of the gastric carcinoma cases had intestinal metaplasia. Intestinal metaplasia co-localized more with intestinal type carcinomas compared with diffuse type carcinomas [75% (21/28) vs 42% (6/14), respectively; P ≤0.05]. The mean apoptotic index in tumor cells was 0.70±0.08. The mean apoptotic index in intestinal metaplasias co-localizing to tumors was significantly higher than that of intestinal metaplasias co-localizing to chronic gastritis (0.70±0.03 vs 0.09±0.01, respectively; P≤0.05). p53 positivity was not observed in areas of intestinal metaplasia adjacent to tumors or chronic gastritis. Intestinal metaplasia areas adjacent to tumors showed lower cytoplasmic bcl-2 positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [55.5% (15/27) vs 70.5% (12/17), respectively]. On the other hand, intestinal metaplasia areas adjacent to tumors showed significantly higher cytoplasmic bax positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [44.4% (12/27) vs 11.7% (2/17), respectively; P ≤0.05]. CONCLUSION: Existence of apoptotic cells on the basis of TUNEL positivity is shown in intestinal metaplasias co-localizing to both diffuse and intestinal type gastric cancers in this study. Our results also suggested bax expression dependent induction of apoptosis especially in intestinal metaplasia areas adjacent to tumors. These findings strongly support the involvement of apoptotic mechanisms in the process of gastric carcinogenesis especially in the transition from intestinal metaplasia to gastric cancer. It may be suggested that induction of apoptosis in intestinal metaplasia areas adjacent to tumors may involve different mechanisms than induction by chronic inflammation.     

Histological and ultrastructural changes induced by selenium in early experimental gastric carcinogenesis

AIM: To investigate the effect and significance of selenium in early experimental gastric carcinogenesis. METHODS: Weaning male Wistar rats were divided randomly into normal control group, experiment control group, low selenium (2 mg/L) group and high selenium (4 mg/L) group. Wistar rat gastric carcinogenesis was induced by /V-methyl-/V-nitro-/V-nitroso guanidine (MNNG) (20 mg/kg) gavage daily for 10 d. Na_2SeO_3 was given by piped drinking 1 wk prior to MNNG gavage. The rats were killed at the 43~(rd) wk. The surface characteristics of gastric mucosa were observed with naked eyes. Histopathologic changes of rat gastric mucosa were observed by HE staining and AB-PAS methods. The changes of cellular ultrastructure were observed under transmission electron microscope. Statistical analysis was carried out by SPSS. RESULTS: The incidence rate of gastric mucosa erosion, hemorrhage and intestinal metaplasia was 0, 45.5%, 66.7%, and 92.9%, respectively (92.9% vs 45.5%, P<0.05) in the normal control group, experiment control group, low selenium group, and high selenium group. Leiomyoma formed in the process of inducement of rat gastric carcinoma. Dietary Na_2SeO_3 (2 and 4 mg/L) slightly increased the incidence rate of leiomyoma (0, 23%, 46.6%, and 46.6%). gastric mucosa did not change in the course of rat gastric carcinogenesis. Dietary Na_2SeO_3 by pipe drinking could expand the intracellular secretory canaliculus of parietal cells and increase the number of endocrine cells and lysosomes. CONCLUSION: Dietary Na_2SeO_3 by pipe drinking aggravates gastric erosion, hemorrhage and promotes intestinal metaplasia of gastric mucosa. The mechanism may be related with the function of parietal cells.     

Immunohistochemical Study of Estrogen Receptor in the Penetrating Type of Early Gastric Cancer

Abstract: The estrogen receptor was studied in a total of 42 cases of gastric carcinoma which included 14 cases of the penetrating type of early gastric carcinoma (PEN), 14 cases of the common type of early gastric carcinomas (EA) and 14 cases of the advanced gastric carcinomas (AD). An immunohistochemical study using the anti-ER-D5 antibody revealed that the detection of estrogen receptor-positive tumor cells was significantly higher in the PEN group and in the AD group than in the EA group. Moreover, the incidence of estrogen receptor immunoreactivity in infiltrative and scirrhous PENs was significantly higher than that in non-infiltrative and non-scirrhous PENs. These results suggests that the estrogen receptor may play an important role in infiltrative proliferation and scirrhous growth in the PENs. Furthermore, the results indicated that ER immunostaining procedures applied to endoscopic biopsy specimens could be useful for the endoscopic diagnosis of PEN-type early gastric cancer.