Biomedical subjects

M Ikeguchi

Publications and source records attributed to M Ikeguchi.

At least 19 recordsLinked to original sources

PubMed2005

The gene expression level of transforming growth factor-beta (TGF-beta) as a biological prognostic marker of hepatocellular carcinoma.

The question that transforming growth factor-beta (TGF-beta) provides a tumor-suppressive or a tumor promoting role is still unknown in hepatocellular carcinoma (HCC). In the present study, we quantitatively investigated the gene expression levels of TGF-beta in liver tissues from patients with HCC. We also evaluated the prognostic importance of TGF-beta gene in HCC patients. A total of 59 patients with primary HCC who underwent hepatectomy between 1993 and 2001 were enrolled. TGF-beta gene expression levels of tumors and of noncancerous livers were analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The percentage of apoptotic cells in tumor cells (apoptotic index: AI) was evaluated with immunohistochemistry. Also the expression of survivin protein (apoptosis inhibitor) in tumors was detected by immunohistochemistry. TGF-beta gene expression levels of tumors were compared with clinicopathological findings of patients. The relative expression level of TGF-beta mRNA of 59 tumor tissues did not differ from those of 8 normal liver tissues or 59 noncancerous liver tissues. The mean AI of 29 tumors with normal expression levels of TGF-beta gene (4%) was significantly higher than that of 30 tumors with low expression levels of TGF-beta gene (2.5%, p = 0.03). Thirteen out of 30 tumors (43%) with low expression level of TGF-P gene showed survivin positive, while only 4 out of 29 tumors (14%) with preserved expression of TGF-beta gene showed survivin positive. This difference was significant (p = 0.012). The overall 5-year survival rate of 29 patients with tumors with preserved TGF-beta gene prolonged to 72% compared with that of 30 patients who had tumors with suppressed TGF-beta gene (58%, p = 0.156). In HCC, TGF-beta gene may play a defensive role against tumor progression by regulating survivin protein expression and by controlling occurrence of spontaneous apoptosis in tumors.

Adult↗

PubMed2004

CD8+ lymphocyte infiltration and apoptosis in hepatocellular carcinoma.

AIMS: Tumour-infiltrating lymphocytes (TILs) play a role in local anti-tumour immunity. Tumour cells may escape from immune surveillance by expressing RCAS1, a receptor-binding cancer antigen expressed on SiSo cells, which inhibits T cell growth. In this study, the correlation between the density of CD8+ TILs, tumour cell apoptosis, and tumour RCAS1 expression was investigated in hepatocellular carcinoma (HCC). METHODS: We obtained tissues from 60 patients with surgically resected HCCs. CD8+ TILS, apoptotic cancer cells, and RCAS1 expressing cancer cells were identified by immunohistochemistry. RESULTS: The density of CD8+ T cells in tumours (mean: 9.5/HPF, HPF: high power field) was significantly less than in non-cancerous hepatic lobules (17.8/HPF, p<0.001) and in relation to the progression of tumour stage. The density of CD8+ T cells in tumours positively correlated with the occurrence of tumour cell apoptosis, but did not correlate with RCAS1 protein expression. CONCLUSIONS: CD8+ TILs may play a role in the occurrence of tumour cell apoptosis in HCC, but CD8+ TILs may not be controlled by RCAS1 in HCC.

Adult↗

PubMed2003

Heparanase gene expression and its correlation with spontaneous apoptosis in hepatocytes of cirrhotic liver and carcinoma.

Heparanase (hep) degrades heparan sulphate proteoglycans (HSPGs), which are the main components of the extracellular matrix. This process has been considered as the first step of tumour invasion or metastasis. However, HSPGs play an important role in signal transduction. Thus, the degradation of HSPGs by hep may suppress tumour cell growth. In the present study, we investigated the clinicopathological importance of enhanced hep mRNA expression in 48 hepatocellular carcinomas (HCCs) and in 48 non-cancerous liver samples obtained from the same patients by quantitative real-time reverse transcriptase polymerase chain reaction (RT-PCR). Spontaneous apoptosis in the hepatocytes was evaluated by immunohistochemistry. The relative hep mRNA expression levels were described as hep/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratios. The hep mRNA levels of HCCs were significantly lower than those of non-cancerous livers (P<0.001). Hep mRNA levels decreased with increasing liver fibrosis. A significant positive correlation between hep gene expression and spontaneous apoptosis was detected. Hep expression in the tumours did not correlate with tumour differentiation or with tumour stage. However, low hep gene expression was associated with a poor disease-free survival of the patients. Thus, hep gene expression may play an important role in programmed cell death and this gene expression may be lost during the malignant transformation of hepatocytes.

Adult↗

PubMed2002

survivin messenger RNA expression is a good prognostic biomarker for oesophageal carcinoma.

Oesophageal squamous cell carcinoma is one of the most malignant tumours. To identify patients with a high risk of recurrence of oesophageal squamous cell carcinoma, we investigated the prognostic significance of survivin mRNA expression in oesophageal squamous cell carcinoma, which has recently been reported to be a good marker for unfavourable prognosis in various tumours. Tumours and non-cancerous epitheliums adjacent to tumours were obtained by surgical resection from 57 patients with oesophageal squamous cell carcinoma. Expression levels of survivin and glyceraldehyde-3-phosphate dehydrogenase mRNA were analysed quantitatively by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The survivin/glyceraldehyde-3-phosphate dehydrogenase ratios of tumours were higher than those of non-cancerous tissues (P=0.0003). Tumour-survivin/glyceraldehyde-3-phosphate dehydrogenase ratio did not correlate with histologic type, lymph node metastasis, and stage of tumours. In 53 surviving patients, the 5-year survival rate of 17 patients with high survivin mRNA expressed oesophageal squamous cell carcinoma (14.1%) was significantly poorer than that of 36 with low survivin mRNA expressed oesophageal squamous cell carcinoma (46.8%, P=0.0018). In these patients, tumour-survivin mRNA expression was recognised as a good marker of cancer recurrence independently from tumour stage. These findings indicate that survivin mRNA expression in oesophageal squamous cell carcinoma may be a good biomarker for identifying patients with high risk of cancer recurrence.

Aged↗

PubMed2002

Expression of survivin mRNA and protein in gastric cancer cell line (MKN-45) during cisplatin treatment.

Survivin is a member of the inhibitor of apoptosis protein (IAP) family. Survivin has been reported to be expressed in many cancers, but not in differentiated normal tissue. Recent studies revealed that survivin correlated with the chemo-resitance of cancer cells. In the present study, the changes in expression levels of survivin messenger RNA (mRNA) and survivin protein in a gastric cancer cell line (MKN-45) during cisplatin (CDDP) treatment were analyzed and compared with the occurrence of apoptotic cell death. Cell growth was inhibited even with a low dose CDDP (0.1 or 1 microg/ml) 1 hr treatment. However, the percentage of apoptotic cells did not change after 48 hr incubation with low dose CDDP. Only with high dose CDDP (10 microg/ml), did the percentage of apoptotic cells explosively increase between 12 and 24 hr treatment. Relative expression levels of survivin mRNA and survivin protein increased after CDDP treatment. The cell expression rates of survivin mRNA after 48 hr treatment with 0.1 and 1 microg/ml of CDDP were 2 to 6 fold higher than that of the survivin mRNA of untreated cells. Also, the relative cell expression level of survivin protein after 24 hr treatment with 0.1 or 1 microg/ml of CDDP was 3 to 6.5 fold higher than that of the survivin protein of untreated cells. These results indicate that survivin expression may correlate with the chemo-resistance of malignant cells.

Apoptosis↗

PubMed2002

Correlation between cathepsin D expression and p53 protein nuclear accumulation in oesophageal squamous cell carcinoma.

AIM: The lysosomal protease cathepsin D has been reported to be associated with tumour progression in malignant tumours. Expression of the gene encoding cathepsin D is known to be stimulated by oestrogen in mammary cancer cells. Recent experiments revealed that a p53 DNA binding site is located in the promoter region of the cathepsin D gene. This fact indicates that cathepsin D expression may correlate with p53 protein expression. The purpose of this study is to evaluate the expression patterns of the cathepsin D and p53 proteins in oesophageal squamous cell carcinoma (SCC). METHODS: In 154 patients with oesophageal SCC, expression of the cathepsin D and p53 proteins was measured in tumours by means of immunohistochemistry using monoclonal antibodies against cathepsin D (clone, 1C11) and p53 (clone, BP53-12). RESULTS: Cathepsin D was detected in tumour cells, although it was not found in normal oesophageal epithelium adjacent to carcinoma. High cathepsin D expression (positive tumour cells > 10%) was detected in 76 of 154 cases (49%) and high p53 nuclear expression (positive tumour cells > 50%) was detected in 70 cases (46%). High cathepsin D expression was significantly associated with invasive tumour growth (p = 0.002), poor prognosis (p = 0.049), and nuclear accumulation of p53 protein (p = 0.001). Overexpression of both p53 and cathepsin D was seen in 45 of the 154 cases (29.2%). In addition, there was a positive correlation between the cathepsin D index (percentage of cathepsin D positive tumour cells) and Ki-67 labelling index (percentage of Ki-67 positive tumour cells) in 154 oesophageal SCCs (rho = 0.257; p = 0.009). However, in multivariate survival analysis, cathepsin D expression by the tumours was not an independent prognostic factor in patients with oesophageal SCC (p = 0.236). CONCLUSIONS: The expression of cathepsin D by cancer cells may play an important role in the invasive growth of oesophageal SCC. Overexpression of both p53 and cathepsin D was seen frequently in tumours; p53 gene abnormalities may correlate with cathepsin D overexpression in oesophageal SCC.

Aged↗

PubMed2002

Re-expression of the cadherin-catenin complex in lymph nodes with metastasis in advanced gastric cancer: the relationship with patient survival.

The cadherin-catenin complex has been recognized as an important factor associated with tumor metastasis. However, the clinical significance of the expression of adhesion molecules in lymph nodes with metastasis remains unclear. The aim of this study was to investigate the clinical significance of the re-expression of the cadherin-catenin complex in metastatic lymph nodes in patients with advanced gastric cancer. Immunohistochemical expression of E-cadherin, alpha- and beta-catenin were analyzed in 96 primary gastric cancers with serosal invasion and in 79 lymph nodes with metastasis. The expression levels of these adhesion molecules in primary tumors and lymph nodes with metastasis were compared. Ninety-four out of 96 primary tumors (98%) showed reduced expression of adhesion molecules. Out of 79 cases with lymph node metastasis, increased expression of one or more adhesion molecules in metastatic foci as compared with primary tumors was detected in 52 cases (66%). Re-expression of adhesion molecules in metastatic lymph nodes was detected in a more advanced stage. The overall 5-year survival rate of the 52 patients who had lymph nodes with metastasis with re-expression of adhesion molecules (8%) was significantly poorer than that of the 27 who had lymph nodes with metastasis without re-expression of adhesion molecules (33%, P = 0.0012). The re-expression of the cadherin-catenin complex in lymph nodes with metastasis may play an important role in the growth of cancer cells in metastatic foci. A comparison of the expression patterns of adhesion molecules between the primary tumor and metastatic lymph nodes may provide new prognostic information for patients with advanced gastric cancer.

Adenocarcinoma↗

PubMed2001

Epigenetic heterogeneity at imprinted loci in normal populations.

Genomic imprinting is the phenomenon by which the two alleles of certain genes are differentially expressed according to their parental origin. Extensive analysis of allelic expression at multiple imprinted loci in a normal population has not performed so far. In the present study, we examined the allelic expression pattern of three imprinted genes in a panel of 262 Japanese normal individuals. We observed differences in the extent of maintenance of allele-specific expression of the three genes. The allelic expression of small nuclear ribonucleoprotein N (SNRPN) was stringently regulated while that of multimembrane-spanning polyspecific transporter-like gene 1 (IMPT1) showed a large degree of variation. Significant biallelic expression of insulin-like growth factor II (IGF2) was observed in about 10% of normal individuals. Our findings add to the accumulating evidence for variable allelic expression at multiple loci in a normal human population. This epigenetic heterogeneity can be a stable trait and potentially influence individual phenotypes.

Alleles↗

PubMed2001

Molecular dynamics study on hydrophobic effects in aqueous urea solutions.

Hydrophobic effects in aqueous urea were analyzed by molecular dynamics simulations. The contribution of solvents to the potential of mean force between two methane molecules was calculated by using molecular dynamics simulations and was compared with the solubility data of hydrocarbons in aqueous urea. Both the simulation results and the solubility data indicated that urea stabilizes methane-methane association. The stabilization was due to increasing the solvation free energies of small hydrocarbons such as methane by addition of urea. The solvation free energies of larger hydrocarbons, on the other hand, are decreased by addition of urea. This effect of the solute size on hydrophobic free energies in aqueous urea was also analyzed by using molecular dynamics simulations by means of division of the solvation process into two parts: the cavity formation and the introduction of the solute-solvent attractive interactions. In the cavity formation, urea increased hydrophobic free energies, and in the introduction of the solute-solvent attractive interactions, urea decreased hydrophobic free energies. The influence of urea on hydrophobic free energies was determined by the balance of effects of the two parts of the solvation process.

Computer Simulation↗

PubMed2001

Micro-lymph node metastasis and its correlation with cathepsin D expression in early gastric cancer.

BACKGROUND AND OBJECTIVES: Limited operations for early gastric cancer (EGC) have been recommended based on data from lymph node (LN) metastasis detected by hematoxylin and eosin (HE) staining. Recently, the clinical importance of micro-LN metastasis has been reported. In this study, the indication of limited operations for EGC was re-evaluated based on the data from micro-LN metastasis detected by cytokeratin (CK) immunostaining. Also, the correlation between micro-LN metastasis and lysosomal acidic protease cathepsin D (CD) expression in primary tumors was evaluated. METHODS: A total of 5,949 LNs from 160 patients with EGC were stained by anti-CK monoclonal antibody (CAM 5.2). Also, the 160 primary EGCs were stained by CD. RESULTS: The incidence of LN metastasis increased from 7.5% (12/160) by HE-staining to 27.5% (44 of 160) by CK immunostaining. The incidence of micro-LN metastasis increased according to the depth of tumor invasion (mucosal cancer: 19% and submucosal cancer: 36.8%) and the size of tumors (< or = 1.0 cm: 5.9%, 1.1-2.0 cm: 25.6%, and > 2.1 cm: 31.7%). The CK-staining patterns were classified into the three subgroups (CK-negative, n = 116; single cell type, n = 27; and clustered type, n = 17). The occurrence of cancer recurrence was significantly higher in clustered type (17.6%) than in single cell type (3.7%) and in CK-negative (0%, P < 0.0001). The mean percentage of CD-positive cancer cells of primary tumors in clustered type (17.2%) was significantly higher than in single cell type (12.3%) and in CK-negative (7.5%, P = 0.0036). CONCLUSIONS: The acidic protease CD may play an important role of cancer metastasis in EGC. The limited operation without lymphadenectomy should be indicated for EGC with CD-negative.

Cathepsin D↗

PubMed2001

Clinical significance of E-cadherin-catenin complex expression in metastatic foci of colorectal carcinoma.

BACKGROUND AND OBJECTIVES: Reduced expressions of cell adhesion molecules (E-cadherin, alpha-catenin, and beta-catenin) has been reported to be associated with tumor metastasis. However, the clinical significance of such adhesion molecules in the metastatic foci remains unclear. In this study, we evaluated the prognostic significance of E-cadherin, alpha-catenin, and beta-catenin expressions in the metastatic foci of patients with colorectal carcinoma. METHODS: The expressions of E-cadherin, alpha-catenin, and beta-catenin were detected immunohistochemically in 105 primary tumors, in 30 metastatic lymph nodes, and 13 metastatic liver tumors from consecutive patients with colorectal carcinoma. RESULTS: Reduced normal expression of E-cadherin, alpha-catenin, and beta-catenin in comparison with normal epithelium was detected in 78 primary tumors, respectively. Patients who had tumors with reduced expression of adhesion molecules showed unfavorable prognosis and the reduced expression of adhesion molecules was detected as one of the independent prognostic factors for patients with colorectal carcinoma. In 30 patients with lymph node metastasis, the increased expression of adhesion molecules in metastatic lymph nodes compared with primary tumors was detected in 13 patients. The prognosis of these 13 patients was poorer than that of remaining 17 patients (P = 0.0296). Also, in 13 patients with liver metastasis, even no significant difference was observed, the mean survival time of 6 patients who had metastatic liver tumors with increased expression of adhesion molecules (10 months) was shorter than that of the remaining 7 patients (16 months; P = 0.1718). CONCLUSIONS: These results suggest that increased expression of the cadherin-catenin cell-cell adhesion system in metastatic foci may play an important role in progression of metastatic colorectal carcinomas.

Adult↗

PubMed2001

Significant correlation between micrometastasis in the lymph nodes and reduced expression of E-cadherin in early gastric cancer.

BACKGROUND: E-cadherin has been recognized as an important factor associated with tumor metastasis. However, the relationship between micrometastasis in the lymph nodes and the expression of E-cadherin in the primary tumor in gastric cancer remains unclear. METHODS: Two consecutive sections of 4522 lymph nodes from 162 patients with early gastric cancer were prepared for simultaneous hematoxylin and eosin (H&E) and cytokeratin (CK) staining. Sections of primary tumors from 135 of these patients were prepared for E-cadherin immunostaining. RESULTS: The incidence of lymph node involvement was significantly increased, from 6.8% (11/162 patients) by H&E staining, to 27% (43/162 patients) by CK immunostaining (P < 0.0001). Micrometastasis in the lymph node was found in 32 of 151 (21%) patients who had no lymph node metastasis evidenced by H&E staining. Micro-lymph node metastasis was frequently found in tumors with a diameter more than 1.0 cm, of those that were poorly differentiated, deeply invaded, showed lymphatic on vascular invasion, and in those that showed reduced expression of E-cadherin. Loss of expression of E-cadherin in the primary tumor was closely correlated with micro-lymph node metastasis. Patients with tumors with micro-lymph node metastasis detected by CK immunostaining had a significantly lower 5-year survival rate (P < 0.01) than those without such metastases. CONCLUSION: Tumors more than 1.0 cm in diameter and those that exhibit poor differentiation, deep invasion (i.e., to the submucosa), lymphatic or vascular invasion, and reduced expression of E-cadherin are risk factors for lymph node metastasis in early gastric cancer. Thus, it is recommended that cancers confined to the mucosa (m-cancers) that are more than 1.0 cm in diameter should not be treated with limited surgery without lymphadenectomy.

Adult↗

PubMed2001

Cyclin D1 expression and retinoblastoma gene protein (pRB) expression in esophageal squamous cell carcinoma.

PURPOSE: Alterations in the cell cycle regulatory cyclin/retinoblastoma protein (pRB) pathway play a important role in tumor progression in esophageal squamous cell carcinoma (ESCC). In the present study, we evaluated the prognostic significance of the combined analysis of cyclin D1 and pRB in ESCC retrospectively. METHODS: Immunoreactivities of cyclin D1 and pRB were evaluated in 148 surgically resected ESCC by use of monoclonal antibodies. Disease-free survival of patients was compared among the four subgroups according to the phenotypes of cyclin D1 and pRB expressions. RESULTS: High immunoreactivities of pRB and cyclin D1 were detected in 64.2% and 40.5% of tumors, respectively. The loss of pRB expression and overexpression of cyclin D1 correlated with short survival. However, these factors were not detected as independently prognostic in multivariate analysis. In 107 surviving patients who underwent curative operation, co-expressed pRB and cyclin D1 (pRB+/cyclin D1 +: 29 patients) were correlated with unfavorable prognosis (disease-free 5-year survival rate: 42.7%) and high cancer recurrence rate (44.8%) compared with that of 40 patients with pRB +/cyclin D1- tumors (70.5% and 27.5%). The disease-free 5-year survival rate of patients with pRB+/cyclin D1- tumors was significantly better than that of other groups (P=0.001). However, the disease-free 5-year survival rate of 29 patients with pRB+/cyclin D1 + tumors was equivalent to that of 29 patients with pRB-/cyclin D1tumors (48.3%), and that of nine patients with pRB-/cyclin D1+ tumors (22.2%, P=0.237). CONCLUSIONS: Our results suggest that overexpression of cyclin D1 may suppress pRB function, and that combined analysis of pRB and cyclin D1 may be a useful parameter of patient prognosis in ESCC.

Aged↗

PubMed2001

Combined resection of invaded organs in patients with T4 gastric carcinoma.

BACKGROUND: To understand the efficacy of gastrectomy combined with the resection of other organs and to refine the indications for this type of surgery, the records of 156 patients with carcinoma of the stomach directly invading adjacent organs or structures (T4 gastric carcinoma) were analyzed retrospectively. METHODS: The patients were divided into three groups, as follows: in group A, curative resection was performed by the combined resection of invaded organs or structures; in group B, although combined resection was performed, curative resection could not be performed because of the extent of lymph node metastasis, liver metastasis, and/or peritoneal metastasis; in group C, combined resection was not performed. RESULTS: In patients with peritoneal or liver metastasis, there was no significant difference in prognosis among the three groups. In patients without peritoneal and liver metastasis, the prognosis of group A was significantly better than that of group B or group C, irrespective of the extent of lymph node metastasis or the number of invaded organs. In these group A patients, the 5-year survival rates of those with localized tumors and no lymph node metastasis, those with localized tumors and lymph node metastasis, those with infiltrating tumors and no lymph node metastasis, and those with infiltrating tumors and lymph node metastasis were 100%, 56.2%, 57.1%, and 13.6%, respectively. CONCLUSIONS: Combined resection of involved organs should be carried out with curative intent in patients with localized gastric cancer or infiltrating gastric cancer without lymph node metastasis.

Adenocarcinoma↗

PubMed2001

A partially unfolded state of equine beta-lactoglobulin at pH 8.7.

The urea-induced unfolding transition of equine beta-lactoglobulin was studied at pH 8.7 using circular dichroism (CD), ultracentrifugation, and gel filtration chromatography. The unfolding transition curves showed that at least one intermediate accumulates at moderate concentrations of urea. Furthermore, analytical ultracentrifugation experiments indicated that the intermediate forms a dimer. Thus, the urea-induced unfolding transition was measured by CD at various protein concentrations and was analyzed by a model assuming the four conformational states (the native, intermediate, dimeric intermediate, and unfolded states). The characteristics of the intermediate are markedly different from those of the intermediate previously observed at pH 4.0 or 1.5. The intermediate at pH 8.7 does not show the intense far-ultraviolet CD suggestive of the nonnative alpha-helix.

Animals↗

PubMed2001

The expression of thymidine phosphorylase suppresses spontaneous apoptosis of cancer cells in esophageal squamous cell carcinoma.

OBJECTIVE: Thymidine phosphorylase (TP) is an enzyme which converts thymidine to thymine. TP is expressed in a variety of human carcinomas and is known to be a potent angiogenic factor. A recent in vitro study indicated that TP is involved in the intracellular apoptotic signal transduction pathway. The aim of this study was to investigate the correlations between the expression of TP, microvessel density (MVD) and the occurrence of spontaneous apoptosis in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of TP, intratumoral MVDs and percentages of apoptotic cancer cells, expressed by the apoptotic index (AI), of 155 tumors from 155 patients with ESCC were analyzed by immunohistochemistry and compared. RESULTS: Positive TP expression in cancer and stromal cells was detected in 89 (57.4%) and 104 (67.1%) cases, respectively. The mean MVD and mean AI of the 155 tumors were 288/mm(2) (range: 36-668/mm(2)) and 2.1% (range: 0-20.4%). The mean MVD of 104 tumors with TP-positive stromal cells (336/mm(2)) was higher than that of 51 tumors with TP-negative stromal cells (188/mm(2), p < 0.001). However, the mean MVD of 89 tumors with TP-positive cancer cells (293/mm(2)) did not differ from that of 66 tumors with TP-negative cancer cells (280/mm(2), p = 0.509). On the other hand, the mean AI of 89 tumors with TP-positive cancer cells (1.2%) was lower than that of 66 tumors with TP-negative cancer cells (3.4%, p < 0.001). However, the mean AI of 104 tumors with TP-positive stromal cells (1.9%) did not differ from that of 51 tumors with TP-negative stromal cells (2.6%, p = 0.058). No significant correlation between the MVDs and the AIs was observed (rho = -0.067, p = 0.409). CONCLUSION: In ESCC, TP may play an important role in tumor progression by increasing microvessels and suppressing apoptosis of cancer cells.

Aged↗

PubMed2001

Clinicopathological findings in patients with gastric adenocarcinoma with familial aggregation.

BACKGROUND/AIMS: The clinicopathological characteristics of gastric cancer (GC) with a positive family history of site-specific GC have not been well discussed. The aim of this study was to estimate the risk of familial aggregation of GC in a hospital-based case-control study and to analyze the clinicopathological characteristics of GC with familial aggregation of GC. METHODS: Our series was comprised of 926 histologically confirmed patients with GC (588 males and 338 females) and 2,052 non-cancer outpatients between 1985 and 1996. The odds ratios (ORs), as estimators of relative risks, together with the corresponding 95% confidence intervals (CIs) for a family history of GC and for a family history of other cancers were calculated. Moreover, the clinicopathological findings of patients with GC who had a GC family history were compared with those of patients with GC who had no GC family history. RESULTS: A positive family history of GC was associated with a statistically significant increase in the risk of GC (OR = 2.15; 95% CI = 1.77-2.63), while no association was observed between the risk of GC and a family history of other cancers (OR = 1.11; 95% CI = 0.91-1.36). The incidence of a multifocal occurrence of GCs was higher in patients with a family history of GC (19.4%) than in patients without a family history of GC (12%, p = 0.005). The risk (OR) of occurrence of multiple cancers in the stomach in patients who had a family history of GC was 1.77 (95% CI = 1.19-2.64). CONCLUSIONS: Our results suggest that a family history of GC seemed to be a risk factor for the development of GC. Further, a family history of GC was found to be associated with a multifocal occurrence of GC.

Adenocarcinoma↗

PubMed2001

Clinicopathological significance of cathepsin D expression in gastric adenocarcinoma.

OBJECTIVE: An estrogen-regulated lysosomal protease, cathepsin D, has been detected in a variety of tissues. This proteinase has been described as closely associated with tumor progression and metastasis in malignant tumors. The purpose of this study was to determine the clinicopathological and prognostic significance of cathepsin D expression in gastric adenocarcinoma. METHODS: In a consecutive series of 478 patients with gastric carcinoma (median follow-up period: 93 months, range: 1-285 months), cathepsin D expression in tumors was quantitatively analyzed with immunohistochemistry using a monoclonal antibody against cathepsin D (clone: 1C11). The percentage of cathepsin-D-positive cancer cells (the CD index) was calculated. In addition, the amount of cathepsin-D-positive stromal cells was evaluated; three grades (high, intermediate, and low) were used for the classification. RESULTS: The mean CD index of 478 tumors was 12.8% (range: 0-100%, median: 8%). The mean CD index of diffuse-type gastric carcinomas (14.9%) was significantly higher than that of intestinal-type carcinomas (10.1%, p < 0.0001). Cathepsin D expression of cancer cells was significantly associated with the depth of tumor invasion in both types. The percentage of tumors with high cathepsin D expression in stromal cells was significantly higher in well-differentiated tumors (25.5%) than in moderately differentiated (12.8%) or in poorly differentiated tumors (19.1%). Cathepsin D expression of stromal cells was significantly associated with the depth of tumor invasion in the intestinal type, in contrast to the diffuse type. Highly expressed cathepsin D in cancer cells was associated with a poor prognosis in both types of carcinoma, but in stromal cells highly expressed cathepsin D was associated to a poor prognosis in the intestinal type only. CONCLUSION: These results indicate that cathepsin D expression in cancer cells may play an important role in tumor progression in diffuse-type gastric carcinoma, whereas in the intestinal type of carcinoma, cathepsin D expression in stromal cells may play an important role in tumor progression.

Adenocarcinoma↗