PubMed HealthSearch

Biomedical subjects

C T Shun

Publications and source records attributed to C T Shun.

At least 19 recordsLinked to original sources

Infrequent hMSH2 mutations in sporadic gastric adenocarcinoma with microsatellite instability.

The status of genetic instability was determined with seven microsatellite markers from 40 patients with primary gastric adenocarcinoma. For those cases with microsatellite instability, alterations of hMSH2 were further investigated by direct sequencing of reverse transcription-polymerase chain reaction products. Twelve (30%) of 40 patients were found to have microsatellite instability. Among them, one patient (1/6, 16.7%) was early gastric cancer and 11 (11/34, 32.4%) were advanced gastric cancer. There were seven patients with diffuse type (7/18, 38.7%), while five (5/22, 22.7%) were intestinal type tumors. The entire coding region of the hMSH2 gene in these 12 affected individuals was amplified and sequenced. Only a 41-year-old female patient with diffuse type advanced gastric cancer showed a GCT to TCT missense mutation at codon 207 with predicted protein change from alanine to serine. Our results indicate that genetic instability plays an important role in gastric tumorigenesis and alterations of the hMSH2 gene are related to only a small portion of sporadic gastric adenocarcinoma with microsatellite instability.

Adenocarcinoma

Genetic alterations in gastric cancer: relation to histological subtypes, tumor stage, and Helicobacter pylori infection.

BACKGROUND & AIMS: A different spectrum of genetic changes including p53, c-erbB-2, c-met, adenomatous polyposis coli (APC), and deleted in colorectal cancer (DCC) is involved in gastric cancer (GC). The aim of this study was to correlate these alterations with histological subtypes, tumor stages, and Helicobacter pylori infection. METHODS: Specimens of 163 patients with GC were immunostained for p53, c-erbB-2, and c-met, and polymerase chain reaction was performed in them to determine loss of heterozygosity (LOH) of APC and DCC. RESULTS: Overexpression of p53 was more frequent in early intestinal than early diffuse GC and was noted in the stage progression of diffuse but not intestinal GC. Overexpression of c-erbB-2 occurred more commonly in intestinal GC and advanced GC of both types. Overexpression of c-met was greater in diffuse GC, particularly at advanced stage. LOH of APC was more common in intestinal GC irrespective of the stage but rarely in diffuse GC. LOH of DCC occurred primarily in advanced intestinal GC and infrequently in early GC or advanced diffuse GC. Alterations of these five genes were not correlated with H. pylori infection. CONCLUSIONS: A distinct genetic pathway exists in gastric carcinogenesis of different histological subtypes and their tumor progression, in which H. pylori infection may play an equal role or no role.

Adenomatous Polyposis Coli

Distinct clinicopathologic characteristics of diffuse- and intestinal-type gastric cancer in Taiwan.

The clinicopathologic features of 221 patients with intestinal-type (IT) gastric cancer were compared retrospectively with those of 290 diffuse type (DT). Intestinal type was characterized by an older mean age (65.0 +/- 10.8 years vs. 56.2 +/- 13 years), a higher male-female ratio (2.56 vs. 1.06), predominance of blood group O (46.2% vs. 31.1%), and frequent habitual smoking (50.7% vs. 31.4%) and drinking (28.5% vs. 17.6%) than did DT. In contrast, DT had a higher frequency of positive history of parent or sibling with gastric cancer (9.3% vs. 4.1%) and blood group A (40.3% vs. 27.6%) than did IT. The distinguishing histologic features of DT included more Borrmann type IV (13.1% vs. 1.3%) but less Borrmann type I (1% vs. 7.2%), more frequent involvement of middle third (26.9% vs. 15.9%) and whole stomach (4.1% vs. 0%), and more peritoneal seeding (15.5% vs. 9%), lymph node metastasis (67.2% vs. 51%), and nerve permeation (34.1% vs. 24.4%), but less Helicobacter pylori infection (55.9% vs. 69.2%) when compared with those of IT. There was no difference in depth of tumor invasion, venous permeation, duodenal involvement, and postoperative survival between IT and DT. These distinct clinicopathologic features between IT and DT in Taiwan suggest the presence of a different pathogenic process for these two histologic subtypes of gastric cancer.

Adenocarcinoma

Increased prevalence of Helicobacter pylori infection among patients affected with intestinal-type gastric cancer at non-cardiac locations.

Previous data on the association of Helicobacter pylori infection with gastric cancer by demographic or histological features are inconsistent due to a univariate analysis of limited case numbers. The aim of the present study was to determine such an association by the use of a large series of patients and multiple variables analysis. The serum IgG antibodies against H. pylori were measured in 397 patients with histologically verified gastric cancer. A multiple logistic regression analysis was used to define the association between seropositivity and demographic or tumour characteristics of gastric cancer. The overall seropositivity of H. pylori was 63%. In univariate analysis, the prevalence was significantly lower among patients with cardia (50%) or diffuse-type (56.6%) cancers than those with non-cardia (64.8%) or intestinal-type (70.3%) cancer (P < 0.05 and P < 0.01, respectively). There was no statistical difference between H. pylori infection rate and gender, age or tumour stage. A multiple logistic regression analysis showed tumour location and histology remained significant factors associated with seropositivity of H. pylori with an odds ratio of approximately 2.0. Analysis of combined histology and location revealed that patients with intestinal-type cancer at non-cardia locations had the highest odds ratio of 3.93 (95% confidence interval (CI): 1.55-10.0) compared with the lowest odds ratio of 0.69 (95% CI: 0.30-1.62) in diffuse cardia cancer (P < 0.005). Our data indicate H. pylori infection in gastric cancer is independently affected by the histological subtype and by tumour location.

Adult

Sialomucin expression is associated with erbB-2 oncoprotein overexpression, early recurrence, and cancer death in non-small-cell lung cancer.

Mucin production, when heavily sialylated, can promote cancer cell invasion and metastasis, and modulate the immune recognition system of the host. To explore the prognostic implication of sialomucin expression in lung cancer, we studied 116 patients with non-small-cell lung cancer (NSCLC). Tumor specimens were stained immunohistochemically with monoclonal antibodies (mAbs) against mucin glycoprotein (17Q2, HMFG2, SM3), and histochemically with periodic acid-Schiff/alcian blue to differentiate neutral mucin from acid mucin, and with high-iron diamine/alcian blue to differentiate sialomucin from sulfomucin. The expression status of two established molecular prognostic factors, the p53 and erbB-2 oncoproteins, were evaluated immunohistochemically. The staining was performed on two separately archived, paraffin-embedded tumor blocks for each patient, with normal lung as a control. Correlations were subsequently made among stains and various clinicopathologic factors. All analyses were blinded, and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling. Associations were established among adenocarcinoma histotype and erbB-2 overexpression, sialomucin expression, and 17Q2 and HMFG2 immunohistochemical positivity (p < 0.05). Sialomucin expression was closely linked to erbB-2 overexpression (p = 0.01). Significant univariate predictors (p < 0.05) of recurrence and cancer death were surgical stage, p53 expression, erbB-2 overexpression, and sialomucin expression. These four factors remained as independent predictors of early recurrence (p < 0.05) after multivariate analysis. For cancer death prediction, p53 and sialomucin expression had a marginal effect. We concluded that sialomucin expression is also a poor indicator of prognosis, which is associated with erbB-2 oncoprotein overexpression, early postoperative recurrence, and cancer death in NSCLC.

Actuarial Analysis

Flat adenoma of the colon: two cases.

Flat adenoma has been frequently reported to have a higher potential for malignant change than other polypoid adenomas. It is an endoscopically visible sessile lesion that consists histologically of an adenomatous change of the colonic mucosa. Detection, diagnosis, and treatment of flat adenoma has not previously been reported in Taiwan. We found such lesions in two patients during colonoscopic examinations as patches of discolored and irregular mucosa. Histopathologic studies revealed adenomas with mild to moderate dysplasia. Patient 1 underwent segmental colectomy; patient 2 underwent an endoscopic strip biopsy. Focal malignant changes were noted in patient 1. Both patients received close follow-up at the outpatient clinic. No recurrence has been seen in patient 1. Patient 2 developed an enlarged sessile lesion with a histologic picture showing a tubular adenoma without malignancy but refused further surgical treatment. This paper outlines the endoscopic and pathologic characteristics of flat adenoma in two patients, and should alert physicians to the importance of early detection and treatment of this lesion.

Adenoma

Overexpression of MUC5 genes is associated with early post-operative metastasis in non-small-cell lung cancer.

Mucin glycoprotein can promote tumor-cell invasion metastasis and modulate the immune recognition of cancer. This study aimed to elucidate the clinical significance of mucin gene overexpression in lung cancer. We collected 60 lung cancer samples and paired non-tumorous lung portions of varying types and stages. Slot-blot analysis with specific anti-sense oligonucleotide probes derived from tandem repeat sequence of MUC1, -2, -3, -4, 5B and 5AC were utilized to compare the amount of mucin gene mRNA in tumor samples with that of the non-tumorous counterparts. A ratio higher than 1.5 for each specific mucin mRNA amount was considered to indicate mucin gene overexpression in tumors. Immunohistochemical staining of monoclonal antibodies against mature airway mucin (17Q2) and MUC1 mucin protein (HMFG2) were also used to analyze mucin protein. The study showed that overexpression of mucin genes frequently occurred in lung cancer (25 out of 60, 41.7%), but that there was no preferential expression of a particular mucin gene or a combination of mucin genes in these tumors. The overexpression of mucin genes and mucin protein had no correlation with tumor stage, nodal stage, histology or pathological differentiation grade. Tumors of smokers had higher MUC5B and MUC5AC mRNA expression ratios than those of non-smokers. Tumors with increased expression of mucin genes tended to be associated with post-operative relapse, especially when MUC5B and MUC5AC genes were overexpressed (p = 0.015 and 0.025, respectively). The study suggests that overexpression of novel tracheobronchial mucin genes may result in an increased likelihood of post-operative lung-cancer recurrence or metastases.

Adult

Primary hemangiopericytoma in the axis bone: case report and review of literature.

OBJECTIVE AND IMPORTANCE: To the best of our knowledge, this is the first reported case of primary hemangiopericytoma in the axis bone. With this report, we attempt to better characterize this uncommon lesion in the vertebral column. CLINICAL PRESENTATION: This report describes a case of primary heman-giopericytoma in the axis bone of a 16-year-old female patient who presented with acute torticollis. Her neurological status was unimpaired. A lateral radiograph of the cervical spine demonstrated an odontoid neck fracture and a C1-C2 rotatory deformity. The magnetic resonance imaging study showed a hypodense lesion with moderate enhancement on T1- and T2-weighted images on the dens and body of the axis with an odontoid neck fracture. Reviewing the literature, primary hemangiopericytoma in the spine is rare; 9 cases of hemangiopericytoma with vertebral bone involvement and 44 cases of this tumor with intraspinal meningeal involvement have been reported. INTERVENTION: The patient was treated with odontoidectomy via the transoral approach, along with posterior fixation using the Halifax clamp. She was followed up 17 months after surgery, and no evidence of tumor recurrence was found. CONCLUSION: The treatment for osseous hemangiopericytoma is still controversial. At present, adequate surgical removal with postoperative radio-therapy is recommended. In addition, although hemangiopericytoma is rare in the spine, it should be kept in mind in the differential diagnosis of spinal tumors.

Adolescent

Intragenic homozygous deletions of MTS1 gene in gastric cancer in Taiwan.

The multiple tumor suppressor 1 (MTS1) and 2 (MTS2) genes, located on chromosome 9p21, have been reported to be deleted or mutated in many malignant cell lines and in a high percentage of some primary carcinomas. To determine whether these genes are altered, and if so, what is the nature of the alterations, in human gastric adenocarcinoma, we investigated their frequency of mutation by Southern blotting, polymerase chain reaction (PCR) and direct sequencing in 55 patients. Furthermore, loss of heterozygosity (LOH) of chromosome 9p21 at the IFNA locus and D9S171 was assessed. Homozygous deletions of exon 1 of the MTS1 gene were identified in 5 of 55 (9.1%) primary tumors. No deletion of MTS2 gene was noted. LOH was observed in 7 (14.3%) of 49 informative cases (5 cases at IFNA locus, 2 cases at D9S171 and one case with combined LOH at D9S171 and homozygous deletion at exon 1 of MTS1). Direct sequencing of PCR products of the MTS1 and MTS2 gene did not reveal any point mutation in these 55 patients. These data indicate that alterations of the MTS1 and MTS2 genes are infrequently encountered. Additional studies of LOH with more microsatellite markers near 9p21 are mandatory to elucidate whether another tumor suppressor gene exists in the vicinity of MTS1 in primary gastric adenocarcinoma.

Blotting, Southern

Primary ovarian carcinoid tumor.

Pure primary ovarian carcinoid tumors are uncommon and only 21 cases have been recorded in the literature. In the past 15 years, we have seen two cases. One was a strumal carcinoid and the other, the case presented here, was a primary ovarian carcinoid tumor arising from the left ovary of a 25-year-old woman who had no carcinoid syndrome. The tumor was made up of pure carcinoid tumor without other teratomatous elements. On light microscopy the neoplasm, composed of uniform tumor cells, was arranged in solid nests or a trabecular pattern. The differential diagnosis included granulosa cell tumor. However, the strongly argyrophilic, chromogranin staining and ultrastructural presence of neurosecretory granules confirmed the diagnosis of primary ovarian carcinoid tumor. After a careful survey of the contralateral ovary and the gastrointestinal tract, the patient underwent a left oophorectomy. Her postoperative course was uneventful. The literature and the pathologic findings are reviewed and discussed, along with the differential diagnosis and treatment of primary ovarian carcinoid tumor.

Adult

Occurrence of microsatellite instability in gastric carcinoma is associated with enhanced expression of erbB-2 oncoprotein.

To investigate the molecular mechanism of gastric carcinogenesis, we examined simultaneously the frequency of microsatellite instability and the immunoreactivities to ras, erbB-2, and p53 in 42 gastric adenocarcinoma tissues. Microsatellite instability, measured by DNA replication error, was detected in 33.3% (14/42) of patients with gastric carcinoma while positive immunostaining was demonstrated in 3.1% (1/32) for ras, 40.5% (17/42) for erbB-2, and 28.6% (12/42) for p53. There was no statistical difference between the intestinal type and the diffuse type of carcinoma with respect to microsatellite instability, ras, or erbB-2 expression. The expression of p53 occurred more frequently in the intestinal type of carcinoma (41.7%, 10/24) than in the diffuse type of carcinoma (11.1%, 2/18; P < 0.01). There was no association between microsatellite instability and ras or p53 expression, while enhanced expression of erbB-2 occurred more frequently in carcinomas with microsatellite instability (64.3%, 9/14) than in those without microsatellite instability (28.6%, 8/28; P < 0.05). Such a strong association between microsatellite instability and erbB-2 oncogene may be responsible for the increase of other oncogenic mutations and tumor progression in gastric carcinogenesis.

DNA, Neoplasm

Comparison between resectable gastric adenocarcinomas seropositive and seronegative for Helicobacter pylori.

The preoperative seropositivity of Helicobacter pylori was determined in 128 patients who had undergone gastrectomy for primary gastric adenocarcinoma during the past 5 years. The overall seroprevalence of H. pylori was 64 per cent. Gastric cancers positive for H. pylori were associated with tumours located in the lower third of the stomach which were of localized type (Borrmann I and II) (P < 0.05), but not with age, sex, blood type, tumour size, invasion depth, lymph node metastases, histological type, DNA ploidy or type of surgery. The cumulative 5-year survival curves after surgical resection were significantly better in patients who were positive for H. pylori. Multivariate analysis revealed that seropositivity for H. pylori was not an independent prognostic factor. Pathological tumour node metastasis staging was the only prognostic indicator. Better prognosis for those with H. pylori-seropositive gastric cancer may be attributed to the more advanced stage of H. pylori-seronegative gastric cancers. The potential role of H. pylori in gastric cancer carcinogenesis and its biological significance warrant further investigation.

Adenocarcinoma

Synchronous primary carcinomas of the endometrium and ovary.

OBJECTIVES: Synchronous carcinomas of the endometrium and ovary may indicate either independently developing neoplasms or metastatic disease. The clinical implications and prognosis of these two categories are quite different. The objectives of this study were to identify and evaluate the empirical criteria and significant therapeutic implications. METHOD: The National Taiwan University Hospital Cancer Registry records and pathological reports from 1977 to 1994 were reviewed. Empirical criteria were used to identify synchronous primary cancers. RESULTS: A total of 322 patients had endometrial cancer and 421 patients had ovarian cancer in our Cancer Registry records. Eleven patients had simultaneous cancer involvement of both the endometrium and ovary. Six cases fulfilled the criteria of synchronous primary carcinomas of the endometrium and ovary. Of these, five were alive and free of disease for 35-144 months (median 94.2 months). The disease-free survival rates between patients with synchronous primary and metastatic cancers of different histologic types showed a statistically significant difference (P = 0.013). No statistical significance was noted for different histologic types (P > 0.5). CONCLUSIONS: The empirical criteria used here were useful in identifying synchronous primary cancers of the endometrium and ovary. The favorable clinical outcome may relate to early detection of early-stage disease and low-grade malignancy with an indolent growth rate. Surgical management with or without adjuvant therapy has a satisfactory outcome in our experience.

Adult

Microsatellite instability in gastric carcinoma with special references to histopathology and cancer stages.

To study the molecular mechanism of gastric carcinogenesis, the frequencies of microsatellite instability were evaluated with seven dinucleotide repeat loci in 59 patients with gastric carcinoma. Microsatellite instability at two or more loci was found in 41.5% (17/41) of advanced gastric carcinoma, 21.4% (3/14) of early gastric carcinoma, but not in remnant gastric carcinoma (0/4), with an overall frequency of 33.9% (20/59). Diffuse gastric carcinoma had a similar prevalence (32.1%, 9/28) to intestinal gastric carcinoma (40.7%, 11/27). The frequency of microsatellite instability in gastric carcinoma was not significantly different with respect to age, sex and Helicobacter pylori infection. Microsatellite instability tended to occur more frequently in cancers of the cardia (62.5%, 5/8) compared with cancers of other stomach regions (31.9%, 15/47), but the difference was not statistically significant. These data suggest that microsatellite instability occurs in early gastric carcinoma and its occurrence increases during tumour progression. Furthermore, its frequency was independent of age, gender, histological types and Helicobacter pylori infection.

Adenocarcinoma

Clinicopathologic characteristics of Helicobacter pyloric seropositive gastric adenocarcinomas.

To compare and characterize retrospectively the clinicopathologic features of gastric cancers with and without previous Helicobacter pylori infection, we determined the preoperative seropositivity of H. pylori in 151 patients who had undergone gastric resection for primary gastric adenocarcinoma between 1988 and 1993. The overall seroprevalence of H. pylori was 60.9%. H. pylori-positive gastric cancers were frequently associated (p<0.05) with macroscopic localized types (Borrmann I and II) in which negative cancer associated with infiltrative types (Borrmann III and IV) and cancer invasion of the duodenum. Multivariate analysis showed that H. pylori seropositivity was not an independent prognostic factor. Pathologic tumor-node-metastases (TNM) stage remained the only prognostic indicator. Our study suggests that H. pylori has a significant impact on the clinically relevant tumor biology of gastric cancer. Investigation along this line is warranted.

Adenocarcinoma