Histological Types Of Gastric Carcinoma Research Articles

The relationship between HER2 expression and 18F-FDG in gastric carcinoma.

The aim of this retrospective study was to evaluate the relationship between human epidermal growth factor receptor 2 (HER2) expression and fluorine-18-fluorodeoxyglucose (18F-FDG) uptake in positron emission tomography with computed tomography (PET/CT) in gastric carcinoma. Gastric carcinoma patients who had 18F-FDG PET/CT scans before treatment were enrolled in this study. Ninety PET/CT images were evaluated before resection or neoadjuvant treatment of 69 patients with gastric carcinoma who had HER2 examination tests. The maximum standardized uptake value (SUVmax) at early (SUV1) and delayed images (SUV2) if any were calculated. In addition, liver SUVmax was measured from the normal liver parenchyma at the dual time (SUV1 liver and SUV2 liver). Tumor-to-liver SUVmax ratio (TLR), retention indexes (RI) from SUVmax, and TLR values obtained from dual-time images were calculated. Histological type of 69 patients were 85.5% adenocarcinoma, 10.1% signet ring cell carcinoma, 2.9% adenosquamous carcinoma, 1.4% mucinous adenocarcinomas. Human epidermal growth factor receptor 2 negative group included 56 (81.2%) patients and the positive group had 10 (14.35%) patients. We did not find any statistical difference for the values of SUVmax and tumor-to-liver SUVmax on all histological types of gastric carcinoma on the dual-phase PET scan. High-level SUV1 was found in the HER2 positive group (8.01±3.11) than negative group (6.15±3.76) in early PET/CT imaging (P=0.043) for adenocarcinoma patients. A positive correlation was observed between HER2 and SUV1 in adenocarcinoma patients (r=0.254,P=0.042). An inverse correlation was determined for histological grade with SUV1 (r=-0.29,P=0.048), TLR1 (r=-0.29,P=0.048) and TLR2 (r=-0.324, P=0.03). Patients with HER2 expression in gastric adenocarcinomas had higher SUVmax values, but no significant difference was found between the groups when the tumor/liver ratio was measured by SUVmax from normal liver parenchyma when background activity was excluded. Signet ring cell carcinoma type and the presence of the signet ring component had no effect on 18F-FDG uptake.

PREVALENCE OF HELICOBACTER PYLORI IN PATIENTS OF GASTRIC CARCINOMA

INTRODUCTION : H. pylori is a gastric pathogen that colonizes approximately 50%-60% of the world's population. Infection with H. pylori causes chronic inflammation and significantly increases the risk of developing duodenal, gastric ulcer disease and gastric carcinoma. This study is undertaken to determine the clinical and pathological profile of gastric carcinoma in our institute and to find out the prevalence of H. pylori infection in gastric carcinoma patients. MATERIALS AND METHODS :We conducted our study in the Department of Surgery, Dr. B. R. A. M. Hospital, Raipur, C.G. over a period of 18 months. It was a hospital based, cross-sectional observational study. During upper GI endoscopy, site of the lesion and macroscopic type of the lesions were identified and recorded. Multiple tissue biopsy samples (>10) were collected from non-necrosed region of cancer. One piece of each paired specimen were immediately subjected to RapidUrease Test dry kit (RUT) for detection of Helicobacter pylori. Further these biopsy specimens were subjected to modified giemsa staining and culture. RESULTS : Out of the 70 cases of gastric carcinoma, the prevalence of H.pylori was 64.28% . The most common age group associated with gastric carcinoma with H.pylori infection was more than 60 years. There was male predominance seen for both gastric carcinoma and gastric carcinoma positive for H.pylori infection. The most common lesion for gastric carcinoma and those positive for H.pylori was ulceroproliferative type. The most common site of stomach involved in cases of Gastric carcinoma associated with H.pylori infection was antrum+pylorus of stomach. The most common histological type of gastric carcinoma associated with H.pylori infection was poorly differentiated adenocarcinoma CONCLUSION : On the basis of our study it is evident that H.pylori is an independent risk factor for gastric carcinoma. .Infection with H. pylori causes chronic inflammation and significantly increases the risk of developing duodenal, gastric ulcer disease and gastric carcinoma.

Gastric cancer with calcifications: A case report

BACKGROUNDMucinous gastric carcinoma (MGC) is a rare histological type of gastric carcinoma. Calcifications, seen on imaging and histopathological preparations, and which are infrequent in other types of gastric carcinoma, are characteristic of MGC. We present a patient with MGC with calcifications of the gastric wall and describe the computerized tomography (CT) features of the lesion and changes in the calcifications before and after chemotherapy.CASE SUMMARYA 61-year-old man was admitted to our hospital in May 2020 because of a large, tender abdominal mass. Abdominal CT showed diffuse, irregular thickening of the gastric walls, with miliary and punctate calcifications. There were metastases to the perigastric and retroperitoneal lymph nodes and also peritoneal seeding. Histological examination of a specimen obtained by endoscopic biopsy showed poorly differentiated calcified signet-ring cell gastric cancer. The patient was clinically staged with T4N+M1 disease. He was treated with docetaxel, cisplatin, and fluorouracil as first-line therapy, irinotecan combined with S-1 as second-line chemotherapy, and programmed cell death protein 1 as third-line therapy. The patient underwent a total of nine cycles of chemotherapy. Follow-up CT scans every 3 mo showed continually increasing calcifications. As of this writing, the patient has survived almost 1 year.CONCLUSIONIn this case report, we describe the histopathological and imaging characteristics of a patient with gastric cancer receiving chemotherapy. Multiple punctate calcifications were seen, which gradually increased during chemotherapy. Several possible mechanisms for the calcifications are described, but further research is needed. Future findings may lead to new approaches for the evaluation and treatment of such tumors.

Diet and gastric cancer

Context: Gastric cancer is the fifth most common malignancy, with a high incidence in Eastern Asian countries. Diet is an important risk factor in the genesis of gastric cancer, and the fact that it is modifiable warrants it to be studied extensively in relation to various clinicopathological parameters of gastric cancer. Aims: The present study was undertaken to study the dietary habits (vegetarian/nonvegetarian) among gastric carcinoma patients in the Indian context. Materials and Methods: We studied 100 consecutive cases of gastric carcinoma excluding tumors at gastroesophageal junction. Clinical data regarding food habits in the patients were collected by personal enquiry. Pathological characteristics including size, site, gross appearance, Lauren's histological type, and the World Health Organization (WHO) histological type were noted. Data analysis was done using Chi-square test. Results: Sixty-nine percent of gastric cancer patients were vegetarians and 31% were nonvegetarians. Statistically significant association between nonvegetarian diet and gastric cancer location at the lesser curvature was found (P ≤ 0.001). No statistically significant association between diet and gross appearance, Lauren's, and WHO histological type of gastric cancer was found. Conclusions: For anatomical locations, most gastric cancers located at lesser curvature had been developed among nonvegetarian patients, whereas we did not observe diet to be related to gross appearance and histological type of gastric carcinoma.

An association study of histological types of gastric carcinoma with Helicobacter pylori infection.

The aim of this study was to study the relation between histopathological classification of gastric carcinoma and Helicobacter pylori (H. pylori) infection. 200 patients with confirmed gastric carcinoma between January 2010 and January 2012 from our hospital were included. All these patients went through endoscopy and histological examinations for gastric carcinoma and immunological test for H. pylori infection. Patients were grouped according to the histological classification, and the infection rates of H. pylori in different groups were compared. Types of gastric cancer that was closely related to H. pylori infection were identified. Infection rate in patients with the intestinal type of gastric cancer was significantly higher compared to those with the diffuse type. For tubular type of carcinoma, the well to medium-differentiated group had a significantly higher infection rate than the poorly differentiated group. Helicobacter pylori infection and histological types were relevant. The effect of H. pylori infection on the intestinal type was more significant than that on the diffuse type. The infection rate of well-differentiated group was higher than that of the poorly differentiated group, which suggested an association between H. pylori infection and the degree of differentiation of tubular cancerous tissue.

Retinoid Receptors in Gastric Cancer: Expression and Influence on Prognosis

Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses, α, β and γ. At present, little is known about retinoid expression and influence on prognosis in gastric cancers. We retrospectively analyzed the expression of the subtypes RARα, RARβ, RARγ, RXRα, RXRβ, RXRγ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using real- time PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). RARα, RARβ, RARγ and RXRγ positively correlated with each other (p<0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p<0.01), with lower RARβ, RARγ and RXRα expression significantly related to advanced stages (p<=0.01). Tumors with poor histopathologic grade had lower levels of RARα and RARβ in different histological types of gastric carcinoma (p<0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p<0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p=0.007, HR=0.41, 95.0% CI 0.21-0.80). Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer.

Gastric carcinoma and chronic gastritis: epigenetic regulation of CDH1 (E-Cadherin), CDKN2A (p16INK4A), PTGS2 (COX-2) and EGFR genes through methylation.

The genetic and epigenetic alterations are being studied as one of the causes of gastric cancer (GC) progression and development. DNA methylation is an epigenetic alteration which leads to suppressor gene silencing and proto-oncogene activation, playing an important role in carcinogenesis. The histological types of gastric carcinoma have different genetic paths and the knowledge of the molecular bases of tumoral progression leads to diagnostic accuracy and attempted therapy. CDH1 (E-cadherin) and CDKN2A (p16(INK4A)) genes are thought to be tumoral suppressor genes and PTGS2 (COX-2) and genes are involved in tumour regulation and growth. In one hand, gene silencing as an epigenetic phenomenon, and in the other hand, gene expression enhancement due to possible demethylation, simultaneously, can facilitate carcinogénesis and tumoral progression. Our aim was to relate CDH1, p16(INK4A), COX-2 and EGFR genes DNA methylation with the several histological types of gastric carcinoma and chronic gastritis. We studied 55 formalin fixed paraffin embedded gastric biopsies: 35 were GC specimens (12 diffuse type, 15 intestinal type and 8 indeterminate type, according to Laurén's classification) and 20 samples had chronic gastritis (CG). The DNA was treated with sodium bisulfite after extraction and then performed Methylation Specific PCR (MSP). Statistical analysis was based on chi-square test and Exact Fisher's test. CpG island methylation was detected in 94% of the GC samples for CDH1, 91% for COX-2, 80% for p16(INK4A) and no methylation was detected in EGFR gene (0%). In CG, CpG island methylation was found in 100% for CDH1 and COX-2 genes, 90% for p16(INK4A) and 20% for EGFR. These results reveal significant differences in EGFR gene methylation distinguishing GC from CG (p < 0, 01), suggesting that gene demethylation leads to malignant transformation and favours the use of tyrosine-kinase inhibitors in its treatment. Genes COX2 e p16INK4A lower methylation in intestinal and diffuse types of GC, favours their different role in respective histogenesis.

Prognostic significance of the expression of MUC1 and collagen type IV in advanced gastric carcinoma

Scirrhous gastric carcinoma is characterized by excessive deposition of collagen in the stroma. However, the clinical significance of this fibrosis of the stomach has not been clarified. The aim of this study was to examine the fibrotic mechanism in several histological types of gastric carcinoma, and the combination of MUC1 and collagen type IV as a possible predictor of patient survival. One hundred and two paraffin-embedded specimens of gastric carcinoma were examined by immunohistochemical staining using monoclonal antibodies against collagen type IV and MUC1. Collagen type IV-positive expression was significantly associated with depth of wall penetration (P = 0.025) and stage (P = 0.023). There was a significant relationship between MUC1-positive expression and interstitial collagen type IV-positive expression (P = 0.035). Survival was shorter for patients with the combination of MUC1-positive expression and interstitial collagen type IV-negative expression than for those with other expression patterns. In patients with differentiated-type advanced gastric carcinoma, the combination of MUC1-positive and interstitial collagen type IV-negative expression may be a marker of unfavourable prognosis.

Prognostic significance of histological type in gastric carcinoma with invasion confined to the stomach wall.

Survival was determined after resection for the two main histological types of gastric carcinoma, intestinal (n = 223) and diffuse (n = 170), in 393 patients with pT1 or pT2 tumours. Lymph node metastases were present in 94 patients. The 10-year survival rate was significantly lower for patients with intestinal-type than for those with diffuse-type carcinoma (72 versus 91 per cent, P < 0.005). In patients without nodal involvement, the 10-year survival rate was still lower for those with intestinal-type cancer (70 versus 94 per cent, P < 0.01). Recurrence of carcinoma was more often by haematogenous dissemination in patients with intestinal-type cancer. Although the results of resection for pT1 or pT2 gastric carcinoma can be acceptable, the introduction of adjuvant therapy based on histological findings may be necessary for patients with the intestinal type of cancer to prevent haematogenous spread of carcinoma to the liver.

Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas.

Intestinal metaplasia (IM) is part of a stepwise sequence of alterations of the gastric mucosa, leading ultimately to gastric cancer, and is strongly associated with chronic Helicobacter pylori infection. The molecular mechanisms underlying the onset of IM remain elusive. The aim of this study was to assess the putative involvement of two intestine-specific transcription factors, CDX1 and CDX2, in the pathogenesis of gastric IM and gastric carcinoma. Eighteen foci of IM and 46 cases of gastric carcinoma were evaluated by immunohistochemistry for CDX1 and CDX2 expression. CDX1 was expressed in all foci of IM and in 41% of gastric carcinomas; CDX2 was expressed in 17/18 foci of IM and in 54% of gastric carcinomas. In gastric carcinomas, a strong association was observed between the expression of CDX1 and CDX2, as well as between the intestinal mucin MUC2 and CDX1 and CDX2. No association was observed between the expression of CDX1 and CDX2 and the histological type of gastric carcinoma. In conclusion, these results show that aberrant expression of CDX1 and CDX2 is consistently observed in IM and in a subset of gastric carcinomas. The association of CDX1 and CDX2 with expression of the intestinal mucin MUC2, both in IM and in gastric carcinoma, indirectly implies that CDX1 and CDX2 may be involved in intestinal differentiation along the gastric carcinogenesis pathway.

Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma

Background & Aims:Interleukin (IL)-1 gene cluster proinflammatory polymorphisms have been associated with development of gastric atrophy and with increased risk of gastric carcinoma. We aimed to determine the association between IL-1 loci polymorphisms and increased risk of gastric carcinoma in samples from a Portuguese population, and to find whether there was any relationship with the histologic types of gastric carcinoma. Methods: In a case-control study including 220 controls and 152 patients with gastric carcinoma (intestinal, 76; diffuse, 37; and atypical, 39), both the IL-1B–511 biallelic polymorphism and the IL-1RN penta-allelic variable number of tandem repeats were genotyped. Results: We found a significant association between the IL-1 polymorphisms and increased risk for tumor development in patients with intestinal-type gastric carcinoma. A trend towards an increased risk of tumor development was also observed in patients with diffuse-type gastric carcinoma. No significant relationship was observed in patients with atypical carcinoma. Carriers of IL-1B-511T and IL-1RN*2 homozygotes had increased risk for developing intestinal-type gastric carcinoma with odds ratios of 2.7 (95% confidence interval [CI], 1.5–4.9) and 3.1 (95% CI, 1.5–6.5), respectively. Statistical analysis showed an interaction between the 2 loci with the risk conferred by the IL-1B-511T allele substantially increased (odds ratio, 9.0; 95% CI, 3.5–23.0) in individuals homozygous for the IL-1RN*2 allele. Conclusions: Our results provide further support to the association between IL-1 gene cluster proinflammatory polymorphisms and increased risk of gastric carcinoma. Furthermore, we found evidence pointing to the existence of a synergistic interaction between the IL-1B and IL-1RN polymorphisms.GASTROENTEROLOGY 2001;121:823-829

Pathology and prognosis of gastric carcinoma

The most important parameters predicting outcome of patients with gastric carcinoma are the depth of wall invasion and the status of lymph node metastasis, but the prognostic significance of histologic type is unclear. The aim of this study was to clarify the prognostic value of two major histologic types of gastric carcinoma, that is well and poorly differentiated types. Histopathologic findings and outcomes of 504 patients with gastric carcinoma were evaluated by well and poorly differentiated types. Well differentiated gastric carcinoma (WGC) included papillary and tubular adenocarcinomas, poorly differentiated medullary carcinoma, and well differentiated mucinous carcinoma; whereas poorly differentiated gastric carcinoma (PGC) included poorly differentiated scirrhous carcinoma, signet ring cell carcinoma, and poorly differentiated mucinous carcinoma. Patients with WGC were characterized by old age, male predominance, tumor location in the lower third of the stomach, small tumor size, and liver metastasis; whereas patients with PGC were distinguished by their tumor location in the middle third of the stomach, serosal invasion, lymph node metastasis, advanced stage, and peritoneal dissemination. The overall 5-year survival rate for patients with WGC was higher than that for patients with PGC (76% vs. 67%; P = 0.058), especially for patients with >/= 10 cm tumors (42% vs. 14%; P = 0.017). The 5-year survival rate for patients with serosa positive but node negative tumors was higher in WGC patients than in PGC patients (83% vs. 59%; P = 0.086); whereas the 5-year survival rate for patients with serosa negative but node positive tumors was lower in WGC patients than in PGC patients (63% vs. 88%; P = 0.008). Multivariate analysis indicated that among pathologic variables of the tumor, histologic type (WGC vs. PGC) was one of the independent prognostic factors. Histologic type is important for estimating the tumor progression and outcomes of patients with gastric carcinoma. In addition to the depth of wall invasion and status of lymph node metastasis, histologic type, including well or poorly differentiated type, should be evaluated in the management of gastric cancer.

Pathology and prognosis of gastric carcinoma

BACKGROUND The most important parameters predicting outcome of patients with gastric carcinoma are the depth of wall invasion and the status of lymph node metastasis, but the prognostic significance of histologic type is unclear. The aim of this study was to clarify the prognostic value of two major histologic types of gastric carcinoma, that is well and poorly differentiated types. METHODS Histopathologic findings and outcomes of 504 patients with gastric carcinoma were evaluated by well and poorly differentiated types. Well differentiated gastric carcinoma (WGC) included papillary and tubular adenocarcinomas, poorly differentiated medullary carcinoma, and well differentiated mucinous carcinoma; whereas poorly differentiated gastric carcinoma (PGC) included poorly differentiated scirrhous carcinoma, signet ring cell carcinoma, and poorly differentiated mucinous carcinoma. RESULTS Patients with WGC were characterized by old age, male predominance, tumor location in the lower third of the stomach, small tumor size, and liver metastasis; whereas patients with PGC were distinguished by their tumor location in the middle third of the stomach, serosal invasion, lymph node metastasis, advanced stage, and peritoneal dissemination. The overall 5-year survival rate for patients with WGC was higher than that for patients with PGC (76% vs. 67%; P = 0.058), especially for patients with ≥ 10 cm tumors (42% vs. 14%; P = 0.017). The 5-year survival rate for patients with serosa positive but node negative tumors was higher in WGC patients than in PGC patients (83% vs. 59%; P = 0.086); whereas the 5-year survival rate for patients with serosa negative but node positive tumors was lower in WGC patients than in PGC patients (63% vs. 88%; P = 0.008). Multivariate analysis indicated that among pathologic variables of the tumor, histologic type (WGC vs. PGC) was one of the independent prognostic factors. CONCLUSIONS Histologic type is important for estimating the tumor progression and outcomes of patients with gastric carcinoma. In addition to the depth of wall invasion and status of lymph node metastasis, histologic type, including well or poorly differentiated type, should be evaluated in the management of gastric cancer. Cancer 2000;89:1418–24. © 2000 American Cancer Society.

Relationship of Tumoral Hyaluronic Acid and Cathepsin D Contents with Histological Type of Gastric Carcinoma

The aim of this work was to evaluate the cytosolic contents of hyaluronic acid (HA) and cathepsin D (CatD) in gastric carcinomas and their possible relationships with the clinicopathological parameters of the tumors. Our study demonstrated a wide variability in the cytosolic levels of HA (mean +/- SEM: 3748 +/- 411 ng/mg protein) and cathepsin D (52 +/- 4 pmol/mg protein) in the tumors of 78 gastric cancer patients. In addition, the tumoral contents of HA and CatD were significantly higher (p<0.005) in diffuse type (HA: 6027 +/- 1099 ng/mg protein; CatD: 75 +/- 13 pmol/mg protein) than in intestinal type (HA: 2735 +/- 242 ng/mg protein; CatD: 42 +/- 3 pmol/mg protein) carcinomas. These data suggest that both markers may contribute to the biological characterization of gastric carcinomas.

Substantial reduction of the gastric carcinoma critical region at 6q16.3-q23.1

Deletions of the long arm of chromosome 6 are a common event in gastric carcinomas. In a previous study, deletion mapping of 6q identified two smallest regions of overlap (SROs) of heterozygous deletions: one interstitial, spanning 12-16 cM, bordered by D6S268 (6q16.3-q21) and ARG1 (6q22.3-q23.1), and one distal to IFNGR1 (6q23-q24), spanning more than 30 cM. Loss of heterozygosity (LOH) of the interstitial SRO was detected in 50% of informative tumors. We analyzed 60 primary gastric tumors with 19 highly polymorphic markers from 6q16.3-q23.3 to delimit the interstitial SRO further. Of the 50 tumors that were informative for at least one locus, 18 (36%) showed allelic imbalance (AI). The overlap of these cases allowed us to define an SRO of approximately 3 Mb flanked by D6S278 and D6S404. AI or LOH of this region occurs in all histologic types of gastric carcinoma and in early stages of development, indicating that loss of a gene from this region of 6q is a crucial step in a main route of gastric carcinogenesis. For cases with retention of 6q, alternative routes of gastric carcinogenesis may exist. Genes Chromosomes Cancer 26:29-34, 1999.

Substantial reduction of the gastric carcinoma critical region at 6q16.3-q23.1

Deletions of the long arm of chromosome 6 are a common event in gastric carcinomas. In a previous study, deletion mapping of 6q identified two smallest regions of overlap (SROs) of heterozygous deletions: one interstitial, spanning 12-16 cM, bordered by D6S268 (6q16.3-q21) and ARGI (6q22.3-q23.1), and one distal to IFNGRI (6q23-q24), spanning more than 30 cM. Loss of heterozygosity (LOH) of the interstitial SRO was detected in 50% of informative tumors. We analyzed 60 primary gastric tumors with 19 highly polymorphic markers from 6q16.3-q23.3 to delimit the interstitial SRO further. Of the 50 tumors that were informative for at least one locus, 18 (36%) showed allelic imbalance (Al), The overlap of these cases allowed us to define an SRO of approximately 3 Mb flanked by D6S278 and D6S404. Al or LOH of this region occurs in all histologic types of gastric carcinoma and in early stages of development, indicating that loss of a gene from this region of 6q is a crucial step in a main route of gastric carcinogenesis. For cases with retention of 6q, alternative routes of gastric carcinogenesis may exist. (C) 1999 Wiley-Liss, Inc.

Expression of CD44 containing variant exon 9 (CD44v9) in gastric adenomas and adenocarcinomas: relation to the proliferation and progression.

The expression of CD44 splice variant containing exon 14 (variant exon 9: CD44v9) was examined immunohistochemically in non-neoplastic mucosa, adenoma and adenocarcinoma of the stomach and analyzed the relation with the expression of Ki-67 antigen and p53 protein. In non-neoplastic gastric mucosa, basolateral membrane of the epithelial cells in the pyloric glands showed the expression of CD44v9. The epithelial cells in the intestinal metaplastic mucosa of the stomach sometimes expressed CD44v9. In the neoplastic lesions, the expression of CD44v9 was detected in 20% (34/170) of the adenomas and 28% (132/478) of the adenocarcinomas, respectively. The incidence of CD44v9 expression did not differ among histological type of gastric carcinoma. Twelve per cent of the adenocarcinomas showed strong expression of CD44v9, whereas non of the adenomas did. The incidence of CD44v9 expression was significantly higher in carcinomas invading into muscularis propria or the cases of stages 3 and 4 in comparison with that in carcinomas limited to submucosa or the stages 1 and 2 cases (p<0.05). The incidence of positive cases was higher in carcinomas with lymph node metastasis than those without metastasis (p<0.05). The expression of CD44v9 was significantly correlated with the expression of Ki-67 (p<0.05). It was also correlated with the expression of p53 protein in the tumor cells (p<0.01). These findings overall suggest that the expression of CD44v9 may be associated with the development as well as progression of the gastric carcinomas.

Cellular and molecular pathology of gastric carcinoma and precursor lesions: A critical review.

The cellular and molecular pathology of gastric cancer and its precursors are reviewed and discussed. Gastric carcinogenesis is a multistep phenomenon, beginning with precancerous conditions. Among these, adenoma is a direct precursor, because of the dysplastic nature of its cells. However, gastric adenoma is relatively rare. Chronic atrophic gastritis (CAG) is the most common precancerous condition, in which intestinal metaplasia often occurs. Carcinoma develops in CAG through stages of hyperplasia and dysplasia involving both metaplastic and non-metaplastic glands. Molecular alterations, including replication error and p53 and APC gene mutation and aneuploidy have been found in some of these conditions, confirming their role in carcinogenesis. Carcinomas of the stomach are heterogeneous in cellular composition. Both intestinal and gastric types of cells are found in all types of tumors, indicating the unique characteristics of gastric cancer. Many molecular lesions have been found in gastric carcinomas. Basic changes involve replication errors, telomerase activity, and aberrant CD44 transcripts. Many other changes often show differences in the frequency of their occurrence between the two major histological types of gastric carcinoma: well differentiated versus poorly differentiated, or intestinal type versus diffuse type. The timing and frequency of these changes in the stomach differ from the timing and frequency in colonic carcinogeneis. Pathological evaluation remains reliable and meaningful, in basic research as well as clinical management. To obtain correlation with molecular alterations, the need for detailed pathologic classification of gastric carcinoma is recognized, taking into account its biologic behavior and grades of cell differentiation.The cellular and molecular pathology of gastric cancer and its precursors are reviewed and discussed. Gastric carcinomas are unique in their heterogeneity in both cellular composition and molecular changes.

Invasive potentials of gastric carcinoma cell lines: role of alpha 2 and alpha 6 integrins in invasion.

The potentials of the two major histological types of gastric carcinoma to invade through extracellular matrices were studied with cell lines. We found that the invasive potential of intestinal-type carcinoma cells (MKN-28 and MKN-74) were higher than those of diffuse-type carcinoma cells (MKN-45 and KATO-III). To investigate whether the alpha 2 and alpha 6 integrin adhesion molecules are responsible for, or involved in carcinoma invasion. We further studied alpha 2 and alpha 6 expression patterns in these two types of cell line. Although fluorescence-activated cell sorting analysis revealed that all cells examined invariably expressed these integrin molecules, their expressional patterns were different among different cell lines. The intestinal-type carcinoma cells expressed integrins mainly along the cell-cell contact region, whereas the diffuse-type carcinoma cells showed a diffuse cytoplasmic pattern of integrin expression. Invasion by MKN-28, MKN-74 and MKN-45 cells through reconstituted basement membrane or type I collagen gel was significantly inhibited (P < 0.05) by 50 micrograms/ml anti-(alpha 2 integrin) or anti-(alpha 6 integrin) monoclonal antibodies. Our results suggest that active invasiveness is stronger in the intestinal-type than in the diffuse-type carcinoma cells and that alpha 2 and alpha 6 integrins play important roles in invasion of both types of gastric carcinoma cell lines.

Immunohistochemical evaluation of lymph node micrometastases from gastric carcinomas.

The clinicopathologic significance of micrometastases to lymph nodes, consisting of a single carcinoma cell or a small cluster of carcinoma cells and confirmed only by special staining, was evaluated in patients with gastric carcinoma. The authors studied 2446 lymph nodes removed during surgery for 109 cases of gastric carcinoma, including Stages I, II, III and IV. Tissue preparations were stained with hematoxylin and eosin (H&E), Alcian blue in combination with periodic acid-Schiff stain, and antibodies against cytokeratin and carcinoembryonic antigen (CEA). Metastases were confirmed in 230 lymph nodes (9.4%) stained with H & E, and an additional 201 lymph nodes (17.6%) had micrometastases identified only by immunostaining for cytokeratin (197 lymph nodes) and/or CEA (66). Carcinomas with micrometastases had significantly worse prognoses at Stage II. Between the two histologic types of gastric carcinoma, the diffuse type had more micrometastases than the intestinal type. The findings of this study indicate that the presence of micrometastases in lymph nodes is an indispensable factor in determining the prognosis of gastric carcinoma patients.