Young Gastric Cancer Research Articles

Age and Severity of Mucosal Lesions Influence the Performance of Serologic Markers in Helicobacter pylori–Associated Gastroduodenal Pathologies

The course of Helicobacter pylori infection and antibody response to CagA in patients with preneoplastic lesions and gastric cancer has not been thoroughly studied. We aimed to study H. pylori infection and antibody response to CagA in patients with non-atrophic gastritis, preneoplastic lesions, and gastric cancer. We studied patients attending one Oncology Hospital and one General Hospital in Mexico City. Diagnosis was based on endoscopy and histopathology in biopsies from six stomach regions. H. pylori infection was assessed by histology and serology, and antibodies against CagA were measured with immunoassay. We included 618 patients, 368 with non-atrophic gastritis, 126 with precancerous lesions, and 65 with gastric cancer; in addition, 59 patients with duodenal ulcer were studied. Detection of infection and IgG against CagA had a significant increase from non-atrophic gastritis to mild and up to advanced stages of metaplasia (P < 0.05), followed by decreased infection and IgG to CagA in patients with gastric cancer (P < 0.05). However, infection and CagA antibodies were associated with young gastric cancer cases. Duodenal ulcer showed a significant association with infection detected by histology and serology, particularly among women, and a trend to associate with IgG to CagA. This study shows that H. pylori infection and CagA are risk markers for intestinal metaplasia. The prevalence of these risk markers decreases in gastric cancer, probably reflecting that infection decreases after advanced atrophy and metaplasia in the gastric mucosa. State of the disease, age, and sex influence the association of H. pylori infection and IgG response to CagA with gastroduodenal diseases.

T2064 Clinicopathological Characteristics and Prognosis of Young Age Gastric Cancer : Analysis of 3,362 Consecutive Gastric Cancer Patients

T2064 Clinicopathological Characteristics and Prognosis of Young Age Gastric Cancer : Analysis of 3,362 Consecutive Gastric Cancer Patients

高齢者胃癌と若年者胃癌の臨床病理学的特徴

高齢者胃癌と若年者胃癌の臨床病理学的特徴

DNA copy number changes in young gastric cancer patients with special reference to chromosome 19.

Only a few cytogenetic and genetic studies have been performed in gastric cancer patients in young age groups. In the present study we used the comparative genomic hybridisation (CGH) method to characterise frequent DNA copy number changes in 22 gastric cancer patients of 45 years or younger and three gastric cancer cell lines established from patients younger than 45 years. Analysis of DNA copy number changes revealed frequent DNA copy number increases at chromosomes 17q (52%), 19q (68%) and 20q (64%). To confirm the CGH results and to characterise the amplicon region on the most frequently amplified chromosome, chromosome 19, we carried out fluorescence in situ hybridisation (FISH) analysis and Southern blot analysis. Fluorescence in situ hybridisation with the bacterial artificial chromosome (BAC) clone mapped to 19q12 indicated a copy number increase in all eight tumour specimens studied. Southern blot analysis of six tumour specimens and three tumour cell lines, with five probes mapped to the 19q12–13.2 region, suggested cyclin E to be one of the candidate target genes in the 19q region for gastric cancer tumorigenesis. Cyclin E protein overexpression was verified in tumours with amplification on chromosome 19. Further studies are required to investigate the biological and clinical significance of 19q amplicon and cyclin E upregulation in gastric cancer of young patients.

Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands.

E-cadherin is involved in the formation of cell-junctions and the maintenance of epithelial integrity. Direct evidence of E-cadherin mutations triggering tumorigenesis has come from the finding of inactivating germline mutations of the gene (CDH1) in hereditary diffuse gastric cancer (HDGC). We screened a series of 66 young gastric cancer probands for germline CDH1 mutations, and two novel missense alterations together with an intronic variant were identified. We then analysed the functional significance of the two exonic missense variants found here as well as a third germline missense variant that we previously identified in a HGDC family. cDNAs encoding either the wild-type protein or mutant forms of E-cadherin were stably transfected into CHO (Chinese hamster ovary) E-cadherin-negative cells. Transfected cell-lines were characterized in terms of aggregation, motility and invasion. We show that a proportion of apparently sporadic early-onset diffuse gastric carcinomas are associated with germline alterations of the E-cadherin gene. We also demonstrate that a proportion of missense variants are associated with significant functional consequences, suggesting that our cell model can be used as an adjunct in deciding on the potential pathogenic role of identified E-cadherin germline alterations.

Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands

Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands

Gastric cancer in young patients with no alarm symptoms: focus on delay in diagnosis, stage of neoplasm and survival

Background: The test and treat strategy for Helicobacter pylori infection has raised some concern since young gastric cancer patients may have no alarm symptoms. In this study the frequency of alarm symptoms was assessed in a series of young gastric cancer patients, as well as the impact of absence of alarm symptoms on delay in diagnosis and stage of gastric cancer at diagnosis and survival. Methods: A retrospective study was carried out on 92 gastric cancer patients ≤ 45 years of age identified from databases in four hospitals between January 1985 and December 2001. Characteristics analysed included duration and features of dyspeptic symptoms, presence of alarm symptoms, time interval from the onset of symptoms to diagnosis, pTNM stage and survival. Results: Of the 92 patients, 54 (58.7%) presented uncomplicated dyspepsia and 38 (41.3%) alarm symptoms. In those with uncomplicated dyspepsia, epigastric pain was the most common complaint (64.1%) followed by vomiting (30.4%), heartburn and nausea. Weight loss was the most common alarm symptom (30.4%), followed by anorexia (10.9%), dysphagia or anaemia (7.6%). The mean delay from first symptoms to final diagnosis was 16.8 ± 13.9 weeks in patients with alarm symptoms and 29.3 ± 39.9 weeks in patients without alarm symptoms (P:ns). Patients without alarm symptoms showed significantly less aggressive gastric cancer compared to patients with alarm symptoms in relation to TNM stage and survival (cumulative 5‐year survival rate: 76% versus 49% P: 0.01). The survival rate, at 5 years, of patients without alarm symptoms, and with a history of dyspepsia of more than 24 weeks, was higher than that in patients with early diagnosis (93.4% versus 66.5%; P: 0.05). Conclusions: A large proportion of young gastric cancer patients present without alarm symptoms. Despite the delay in diagnosis, these patients have a better outcome than those with alarm symptoms. Thus the delay in diagnosis of patients without alarm symptoms does not affect survival.

Microsatellite instability and/or loss of heterozygosity in young gastric cancer patients in Italy.

Gastric cancers are rarely diagnosed before the age of 40 years and the incidence reaches a peak during the 7th decade in the general population. A molecular mechanism of early tumor onset may be determined by comparing microsatellite instability (MSI), indicative of error-prone mismatch repair, and loss of heterozygosity (LOH) between gastric cancers in patients < or = 40 years of age and those of older ages. Three to 5 chromosomal loci, where MSI and/or LOH are commonly found in gastric cancers in the general population, were examined in formalin-fixed, paraffin-embedded samples from 102 patients < or = 40 years of age using a polymerase chain reaction-based non-radioactive screening method. MSI and/or LOH at a minimum of 1 locus were detected in 11/102 patients. The frequency of MSI and/or LOH at the D11S904 locus was significantly higher than that at the D2S119, D2S123, D5S409 and IFNA regions. No preferential genetic changes at the D11S904 locus were observed in elderly patients. Among several clinicopathological variables, a statistically significant association with MSI and/or LOH was observed only for tumors located at the cardia, compared with tumors at the antrum and the corpus. Our findings suggest that a unique mechanism may be involved in increasing the susceptibility of the D11S904 locus for either MSI or LOH, especially for cardia tumors in young patients. Early onset of gastric cancers in patients < or = 40 years of age is associated with genetic changes at preferential chromosomal loci, including D11S904.

Microsatellite instability and/or loss of heterozygosity in young gastric cancer patients in Italy

Microsatellite instability and/or loss of heterozygosity in young gastric cancer patients in Italy

Gastric cancer in young patients

Background: Delayed diagnosis, a high rate of histologically undifferentiated types of tumors, and rapid disease progression are frequently cited as the main reasons for the poor prognosis of gastric cancer in young patients. An improved prognosis has been anticipated for young gastric cancer patients because of recent improvements in digestive tract diagnostic techniques. This retrospective study was designed to determine whether these trends have had an impact on young Japanese patients with gastric cancer, and to further elucidate differences in clinicopathologic features between elderly and young patients. Methods: From 1984 to 1995, 1654 patients with gastric cancer were admitted to our hospital. Of these, 86 patients (5.2%) were less than 40 years of age (young group). The clinicopathologic features of this young group were reviewed retrospectively, using hospital records, and compared with those of older patients (n = 499 [29.4%], 60 to 69 years of age). Results: The young group contained significantly higher percentages of female patients, epigastric pain symptoms, depressed superficial type lesions, mucosal invasion, and poorly differentiated histology; percentages of hepatic metastasis and venous invasion were lower. Survival rates for all patients and for the resected cases were significantly better in the young group (p = 0.035 and 0.017 respectively). The percentage of early stage stomach cancers for the group less than 40 years of age was 49.0% in 1984–89, but had risen to 60.9% by 1990–95. Conclusions: Early diagnosis has improved the prognosis of young gastric cancer patients. Furthermore, these data show a recent shift in stage distribution; additional prognostic improvement is anticipated for young patients with early gastric cancer.

Frequent microsatellite instability and loss of heterozygosity in the region including BRCA1 (17q21) in young patients with gastric cancer.

It is known that nearly 5% of gastric carcinomas arise under the age of 40. To elucidate genetic alterations in these patients, we performed studies using microsatellite assay in 27 gastric cancers under 35 years of age, composed of 5 well and 22 poorly differentiated adenocarcinomas. We detected replication errors (RERs) in 18 (67%) of 27 tumors, but no germline mutation in DNA mismatch repair genes (hMLH1 and hMSH2), except fory 3 somatic mutations in the hMLH1 gene. Loss of heterozygosity (LOH) at D17S855, located on chromosome 17q21 (BRCA1), was detected in 8 (40%) of 20 informative cases. In 12 (44%) of 27 cases, LOH on chromosome 17q12-21 including the BRCA1 was found in several neighboring markers in this region, while no mutation was found in the BRCA1 gene. Four (40%) of 10 scirrhous type gastric cancers exhibited wide allelic deletions on chromosome 17q12-21. These results overall suggest that young gastric cancer patients display highly frequent micro-satellite instability that might be due to defect of DNA repair system rather than hMLH1 and hMSH2. In addition, chromosome 17q12-21 including BRCA1 locus may contain a candidate for tumor suppressor gene, particularly in scirrhous type gastric cancers arising in young patients.