OBJECTIVETo study the role of arginase-1 (Arg-1) expression in differential diagnosis of hepatocellular carcinoma (HCC), Arg-1 staining pattern in clear cell neoplasm (HCC and non-HCC) and Arg-1 expression in non-hepatocellular tumors.

METHODSSeventy-eight cases of HCC (including 8 cases of clear cell type and 70 cases of non- clear cell type) and 246 cases of non-hepatocellular neoplasms (including 29 cases of metastatic tumors such as breast cancer, nasopharyngeal carcinoma and neuroendocrine carcinoma, 77 cases of tumors with clear cell changes such as malignant melanoma, clear cell renal cell carcinoma and alveolar soft part sarcoma, and 140 cases of other types of tumors such as ovarian endometrioid adenocarcinoma, pituitary tumor and thyroid papillary carcinoma) were studied.Immunohistochemical study for Arg-1 was performed on the paraffin-embedded tumor tissue.

RESULTSIn HCC, Arg-1 demonstrated both cytoplasmic and nuclear staining, with an overall sensitivity of 96.2% (75/78).In well, moderately and poorly differentiated HCC, the sensitivity was 15/15, 100% (41/41) and 86.4% (19/22), respectively. That was in contrast to negative staining for Arg-1 in all the 29 cases of metastatic tumors studied. The sensitivity, specificity, positive predictive value and negative predictive value of Arg-1 in distinguishing HCC from metastatic tumors was 96.2%, 100%, 100% and 90.6%, respectively. Cytoplasmic and membranous staining was observed in clear cell type of HCC. The overall sensitivity of Arg-1 expression in the 77 cases of tumors with clear cell changes was 14.3% (11/77), including 8/15 for malignant melanoma, 2/4 for ovarian clear cell carcinoma and 1/1 gall bladder adenocarcinoma with clear cell component.In malignant melanoma and ovarian clear cell carcinoma, only cytoplasmic staining was demonstrated. There was no expression of Arg-1 in the 140 cases of other tumor types studied.

CONCLUSIONSArg-1 is a sensitive and specific marker for HCC.It is a potentially useful immunohistochemical marker in distinguishing HCC from metastatic tumors. Though also expressed in malignant melanoma and ovarian clear cell carcinoma, Arg-1 shows a different staining pattern as compared with that in HCC.

Adenocarcinoma ; enzymology ; Adult ; Aged ; Arginase ; metabolism ; Carcinoma, Hepatocellular ; enzymology ; pathology ; secondary ; Cell Differentiation ; Diagnosis, Differential ; Female ; Gallbladder Neoplasms ; enzymology ; Humans ; Liver Neoplasms ; enzymology ; pathology ; secondary ; Male ; Melanoma ; enzymology ; Middle Aged ; Ovarian Neoplasms ; enzymology ; Stomach Neoplasms ; enzymology ; pathology

BACKGROUND: Helicobacter pylori (H. pylori) has been considered a definitive carcinogen in gastric cancer. Telomerase is activated in gastric cancer and some premalignant gastric lesions, including intestinal metaplasia (IM). In this study, we evaluated the relationships of both H. pylori infection and telomerase activity with endoscopic and histologic features in IM. The effects of H. pylori eradication on endoscopic, histologic and biochemical changes were evaluated. METHODS: Endoscopic biopsies were obtained from 43 patients with IM for rapid urease, histologic and telomerase tests. The endoscopic and histologic features, H. pylori infection and telomerase were assessed. After H. pylori eradication, 15 patients were re-evaluated and compared after 4 months. RESULTS: Thirty-four (79.1%) patients were infected with H. pylori. The incidence of H. pylori infection was borderline correlated to the severity of IM (p=0.076). Telomerase was elevated in eight (18.6%) patients. Telomerase tends to be high in subtype III and endoscopic grade III of IM. After H. pylori eradication, endoscopic extent (p=0.039) and histologic severity (p=0.074) showed improvements, and telomerase decreased significantly (p=0.0001). CONCLUSION: Our data suggest that telomerase is associated with the severity and extent of IM and that H. pylori eradication improves the endoscopic and histologic features in IM, and decreases telomerase activity. H. pylori eradication can be considered one of the methods to prevent gastric cancer in patients with H. pylori-infected IM. Further long-term and large-scaled study will be needed.
Female ; Helicobacter Infections/*enzymology ; *Helicobacter pylori ; Human ; Intestinal Mucosa/enzymology/microbiology/*pathology ; Male ; Metaplasia/enzymology/microbiology ; Middle Aged ; Precancerous Conditions/enzymology/microbiology ; Stomach Neoplasms/*enzymology/microbiology ; Telomerase/*metabolism

BACKGROUND/AIMS: Recent studies have shown that cyclooxygenase-2 (COX-2) may be involved in the process of invasion, growth and apoptosis in colorectal carcinoma and in the growth and tumorigenesis in familial adenomatous polyposis. This study was conducted to determine the significance of the expression of COX-2 in gastric and colorectal adenomas. METHODS: Forty-nine samples of gastric adenoma and fifty-seven samples of colorectal adenoma were obtained by endoscopic mucosal resection or polypectomy from 106 patients from January 2000 to July 2003. COX-2 expression was determined by immunohistochemistry. Correlation between COX-2 expression and several clinical factors were compared in each gastric and colorectal adenomas. RESULTS: The expression of COX-2 in epithelial cells was significantly higher in the group with large adenoma (>1 cm) compared with the group with small adenoma ( Adenoma/enzymology/*pathology ; Aged ; Colorectal Neoplasms/enzymology/*pathology ; English Abstract ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prostaglandin-Endoperoxide Synthase/*analysis ; Stomach Neoplasms/enzymology/*pathology

OBJECTIVETo study the thymidine phosphorylase (TP) expression in different types of cancer and its correlation with tumor microvessel density (MVD).

METHODSThe expression of TP and MVD was detected by immunohistochemistry method. In a series of 251 cancer patients there were 48 patients with gastric cancer, 53 with colorectal cancer, 47 with breast cancer, 56 with cervical cancer, 47 with lung cancer. Normal gastric (n = 25), colorectal (n = 25), cervical (n = 17) and lung (n = 25) tissues around the cancer were also examined.

RESULTSThe TP expression rate was 64.6% in gastric cancer, 67.9% in colorectal cancer, 80.9% in breast cancer, 82.1% in cervical cancer, and 63.8% in lung cancer, which was significantly higher than that in normal tissues (P = 0.0000). TP expression was positively correlated with MVD in gastric, colorectal, breast, and cervical cancers. The correlation was not statistically significant in lung cancer.

CONCLUSIONThis study indicates that TP overexpression in cancer may be associated with tumor angiogenesis.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; blood supply ; enzymology ; Colorectal Neoplasms ; blood supply ; enzymology ; Female ; Humans ; Male ; Middle Aged ; Neovascularization, Pathologic ; pathology ; Stomach Neoplasms ; blood supply ; enzymology ; Thymidine Phosphorylase ; metabolism ; Uterine Cervical Neoplasms ; blood supply ; enzymology

Gastric CD30-positive anaplastic large-cell lymphoma is a very rare disease. It is sometimes difficult to distinguish it from undifferentiated carcinoma, sarcoma and so on. We report here on a case of primary gastric anaplastic large-cell lymphoma. A 50-yr-old woman complained of epigastric pain and severe chest pain for 1 week. The gastroendoscopic examination revealed geographic mucosal irregularities with shallow ulceration at the antrum. She underwent a total gastrectomy. The gross finding of the resected stomach was an 8 x 4.5 cm sized ulceroinfiltrative lesion at the pyloric antrum along the lesser curvature. The microscopic examination revealed diffuse and solid proliferations of large atypical cells with pleomorphic nuclei. Immunohistochemically, the tumor cells were positive for CD30, vimentin and CD3, and this was a finding compatible with anaplastic large-cell lymphoma. To the best of our knowledge, this is the first such reported case in Korea.
Antigens, CD30/*metabolism ; Female ; Humans ; Immunohistochemistry ; Korea ; Lymphoma, Large-Cell/enzymology/*immunology/*pathology ; Middle Aged ; Protein-Tyrosine Kinase/metabolism ; Stomach Neoplasms/enzymology/*immunology/*pathology

OBJECTIVETo investigate the association of AKR1B10 expression in gastric cancer tissues with clinicopathologic features and prognosis of gastric cancer patients.

METHODSReal-time polymerase chain reaction (RT-PCR) was conducted to detect AKR1B10 mRNA expression in gastric cancer and adjacent gastric mucosa tissues (n=36). AKR1B10 protein expression was measured by immunohistochemistry in primary gastric cancer tissues (n=100) and non-tumorous gastric mucosa tissues (n=70).

RESULTSRT-PCR results confirmed that AKR1B10 was significantly down-regulated in gastric cancer tissues compared with that in paired adjacent mucosa [8.3% (3/36) vs. 91.7% (33/36), P=0.000]. Immunohistochemistry revealed that the percentage of AKR1B10 positive specimens in gastric carcinoma was lower than that in normal specimens [33.0% (33/100) vs. 92.9% (65/70), P=0.000]. The frequencies of positive AKR1B10 in patients was significantly correlated with tumor size (P=0.000), invasive depth (P=0.004), lymph node metastasis (P=0.028), distant metastasis (P=0.031) and TNM stages (P=0.000). The 5-year survival rate of positive AKR1B10 group was significantly higher as compared to negative group (60.6% vs. 32.8%, P<0.01).

CONCLUSIONThe down-regulation of AKR1B10 expression in gastric cancer may be associated with the progress of gastric cancer is suggestive of poor prognosis.

Adult ; Aged ; Aged, 80 and over ; Aldehyde Reductase ; genetics ; metabolism ; Female ; Gastric Mucosa ; enzymology ; pathology ; Humans ; Male ; Middle Aged ; Prognosis ; RNA, Messenger ; genetics ; Stomach Neoplasms ; diagnosis ; enzymology ; pathology

BACKGROUND: Cyclooxygenase (COX) -2 is the rate-limiting enzyme in prostaglandin synthesis. An increased expression has been implicated in the development and progression of human gastric cancers and colorectal adenomas and cancers. This study aimed to determine the involvement and association of COX-2 and Bcl-2 in precancerous gastric adenomas. METHODS: Seventy-nine gastric polyps were obtained by endoscopic mucosal resection or polypectomy from January, 2000 to July, 2003. Immunohistochemical expression of COX-2 and Bcl-2 was observed, and their relationships with various clinicopathological factors were analyzed. RESULTS: Histologically, 13 hyperplastic polyps and 66 tubular adenomas, of which 17 showed high-grade dysplasia, were observed. Increased COX-2 expression was observed in low-grade and high-grade tubular adenomas compared to hyperplastic polyps (p=0.004 and p=0.001, respectively). COX-2 expression was significantly higher in larger (> 1 cm) compared with smaller (< or=1 cm) tubular adenomas (p=0.034), but no relation was observed in hyperplastic polyps. While Bcl-2 expression differed significantly according to histology, increased Bcl-2 expression was observed especially in COX-2 positive low-grade tubular adenomas. CONCLUSION: COX-2 expression increased in a size-dependent manner in tubular adenomas, suggesting a role in polyp growth. The increased expression of Bcl-2 in tubular adenomas, especially in COX-2 positive tubular adenomas, suggests that COX-2 action may be related to Bcl-2 expression.
Stomach Neoplasms/*enzymology/pathology ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Middle Aged ; Male ; Immunohistochemistry ; Humans ; Disease Progression ; Cyclooxygenase 2/*metabolism ; Adenoma/*enzymology/pathology

Thymidine phosphorylase (TP) has shown to be up-regulated in several cancers and to play a role in angiogenesis and invasion. Most studies regarding TP have focused on cancer cells. Recently, evidences suggest that TP in cancer-infiltrating inflammatory cells (CIICs) also affect the cancer cell behavior. To evaluate the significance of TP expression of CIICs in gastric cancer, we assessed TP expression of cancer cells and CIICs separately using immunohistochemical assay on 116 paraffin-embedded tissue samples from stomach cancer patients and investigated their clinical significance. When subjects were divided into 4 groups according to the TP expression: cancer/matrix (+/+), C/M (+/-), C/M (-/+), and C/M (-/-), intratumoral microvessel density scores were higher in the C/M (+/-) group than in the C/M (-/-) group (p=0.02). For lymph node metastasis and survival, there were no significant differences among the 4 groups. However, there were significant differences in survival (p=0.035) and LN metastasis (p=0.023) between the two groups divided by TP expression of CIICs alone irrespective of TP expression of cancer cells. Taken together, this study suggested the TP expression in CIICs could affect lymph node metastasis and patients' survival in gastric cancer.
Adult ; Aged ; Female ; Humans ; Immunohistochemistry ; Inflammation/*enzymology/pathology ; Kaplan-Meiers Estimate ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating/*enzymology/pathology ; Male ; Microcirculation/pathology ; Middle Aged ; Neovascularization, Pathologic ; Prognosis ; Stomach Neoplasms/blood supply/*enzymology/mortality/pathology ; Thymidine Phosphorylase/*metabolism

OBJECTIVETo study the level of expression of Caspase-3 protein in precancerous lesions of stomach and its relation to gastric carcinogenesis.

METHODSFormalin-fixed paraffin embedded tissues from 184 cases of gastric mucosa biopsy and surgically removed specimens, including gastric cancer (GC, N = 20), chronic atrophic gastritis (CAG, N = 6), atrophic gastritis with intestinal metaplasia (IM, N = 31), atrophic gastritis with dysplasia (DYS, N = 114) and normal controls (N = 13) were examined for expression of Caspase-3 protein and Ki-67 index by SABC immunohistochemistry, and for apoptosis by TdT-mediated dUTP biotin nick end labeling (TUNEL) method. Caspase-3, Ki-67 and TUNEL index were compared in different stages of gastric precancerous lesions and their correlation was analyzed.

RESULTSThe positive index of Caspase-3 protein in severe DYS (29.8% +/- 3.9%) showed no significant difference compared with that in GC (26.9% +/- 3.0%, P > 0.05), but was significantly lower than that in low (58.3% +/- 4.2%) and moderate grade DYS (50.4% +/- 4.8%), CAG (68.3% +/- 3.3%) and IM (70.9% +/- 4.3%, P < 0.05). Caspase-3 positive index was significantly correlated with that of apoptosis detected by TUNEL (r = 0.94, P < 0.05). Ki-67 index in Caspase-3 protein positive group (18.3% +/- 2.2%) was significantly lower than that in Caspase-3 negative group (48.9% +/- 3.1%, P < 0.05).

CONCLUSIONCaspase-3 protein expression was upregulated in CAG with or without IM and low or moderately low in DYS, while down-regulated in severe DYS and gastric carcinoma, and significantly positively correlated with cell apoptosis. It is suggested that down-regulated expression of Caspase-3 protein somehow contributes to gastric carcinogenesis through an imbalance between cell apoptosis and proliferation.

Adult ; Aged ; Apoptosis ; Caspase 3 ; metabolism ; Down-Regulation ; Female ; Gastric Mucosa ; enzymology ; metabolism ; pathology ; Gastritis, Atrophic ; enzymology ; metabolism ; Humans ; Ki-67 Antigen ; metabolism ; Male ; Metaplasia ; Middle Aged ; Precancerous Conditions ; enzymology ; metabolism ; Stomach Neoplasms ; enzymology ; metabolism

OBJECTIVETo investigate the expression of PTEN and Caspase-3 in malignant lymphoma of the stomach and explore their role in progression of primary gastric malignant lymphoma.

METHODSFormalin-fixed paraffin embedded tissues from 56 cases of primary gastric malignant lymphoma and their adjacent non-tumor mucosa were evaluated for PTEN and Caspase-3 protein expression by streptavidin-biotin-complex (SABC) immunohistochemistry. Their expression was compared with clinical tumor parameters with the relationship between PTEN and Caspase-3 expression concerned as well.

RESULTSThe positive rate of PTEN expression in primary gastric lymphomas (50.0%, 28/56) was significantly lower than that in adjacent non-tumor gastric mucosa (96.4%, 27/28) (P < 0.05). Meanwhile, 43 of 56 (76.8%) gastric lymphomas indicated Caspase-3 expression, less than that in adjacent non-tumor mucosa (93.5%, 29/31) (P < 0.05). The expression of PTEN was negatively correlated with invasion and lymph node metastasis of gastric lymphoma (P < 0.05), while the Caspase-3 expression was negatively associated with the latter one (P < 0.05). Additionally, the PTEN expression was positively correlated with Caspase-3 expression in the primary gastric malignant lymphoma (P < 0.05).

CONCLUSIONSThe down-regulated expression of PTEN and Caspase-3 played an important role in progression of primary malignant gastric lymphoma. PTEN, as a molecular marker of pathobiological behaviors of tumor, contributes to tumor progression by increasing cell mobility and angiogenesis, as well as decreasing cell adhesion and apoptosis.

Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Caspase 3 ; Caspases ; metabolism ; Down-Regulation ; Female ; Gastric Mucosa ; enzymology ; Humans ; Lymphatic Metastasis ; Lymphoma ; enzymology ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; PTEN Phosphohydrolase ; Phosphoric Monoester Hydrolases ; metabolism ; Stomach Neoplasms ; enzymology ; pathology ; Tumor Suppressor Proteins ; metabolism