Enhanced effect of gastrin on rat stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.

This study deals with the effects of gastrin on the incidence of gastric tumors in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine. Inbred Basel-Wistar rats received N-methyl-N'-nitro-N-nitrosoguanidine in drinking water (50 micrograms/ml for 32 weeks) in order to produce gastric carcinoids. A treatment with s.c. injection of pentagastrin (300 micrograms/kg, once daily for 4 weeks) was started at the beginning of N-methyl-N'-nitro-N-nitrosoguanidine treatment simultaneously, on the 4th, 8th, 16th, and 32nd week after start of N-methyl-N'-nitro-N-nitrosoguanidine treatment, respectively. At autopsy, from the 55th to 60th week after start of the experiment, only in the eighth-week group of gastrin-treated rats was the incidence of gastric carcinoid significantly higher than in the gastrin-untreated group of rats receiving N-methyl-N'-nitro-N-nitrosoguanidine alone. The incidence of adenocarcinoma in the glandular stomach also was high only in the fourth-week group of gastrin-treated rats. However, these effects could not be seen in other gastrin-treated or untreated groups of rats. The data suggest that gastrin treatment in the early stage of rat stomach carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine is effective in increasing the development of gastric tumors.

Prognostic evaluation of mucin-5AC expression in intrahepatic cholangiocarcinoma, mass-forming type, following hepatectomy.

AIM: This study aimed to investigate the clinicopathological predictors of survival in patients with intrahepatic cholangiocarcinoma, mass-forming type (ICC-MF), following curative intent hepatectomy. METHODS: Clinical characteristics and outcomes were analyzed in a series of 42 patients who underwent curative hepatectomy for ICC-MF between February 1987 and December 2012. The relationship between immunohistochemical expression profiles of mucin (MUC) core proteins (MUC2, MUC5AC, and MUC6) and surgical outcomes was examined. RESULTS: The overall median follow-up period was 2.6 years (0.2-17.9). Bile duct reconstruction (p = 0.017), lymph node metastasis (p = 0.049), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.003) were identified as significant adverse predictors of overall survival by univariate analysis. Bile duct reconstruction (p = 0.048), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.005) were found to be independent predictors of poor prognosis by multivariate analysis. Maximal mass diameter ≥5.0 cm (p = 0.011) was found to be an independent predictor for the tumor recurrence. There was a strong correlation between MUC5AC expression and lymph node metastasis (p = 0.021). MUC6 expression was more frequent in patients with concurrent MUC5AC expression (p = 0.019). CONCLUSIONS: MUC5AC expression was significantly related to long-term prognosis and aggressive tumor development, and may be a useful prognostic marker.

Cathepsin D expression as a possible predictor of lymph node metastasis in submucosal colorectal cancer.

The aim of this study was to clarify the usefulness of cathepsin D expression as a predictor of lymph node metastasis in submucosal colorectal cancer (CRC). Cathepsin D expression was examined immunohistochemically in cancer and stromal cells located at the deepest portion of 254 invasive tumours that had been resected from patients with submucosal CRC. In cancer cells, the expression was classified according to differences in intracellular localisation: polarity positive, apical type (PA); polarity positive, basal type (PB); polarity negative (PN); or no expression (NE). Lesions with PN or NE expression showed a significantly higher incidence of lymph node metastasis than those with PA or PB expression. Alternatively, lesions with positive expression in stromal cells showed a significantly higher incidence of lymph node metastasis than that of those with negative expression. None of the lesions with PA or PB expression and negative expression in stromal cells had metastasised to the lymph node. In conclusion, analysis combining cathepsin D expression in cancer and stromal cells may be a quite useful predictor for lymph node metastasis and may broaden the indications for curative endoscopic treatment of submucosal CRC.

Expression of telomerase component genes in hepatocellular carcinomas.

The aim of the study was to clarify the role of telomerase component genes in hepatocarcinogenesis and to examine both the relationship between the expression of telomerase component genes and histological differentiation in hepatocellular carcinoma (HCC) and the relationship between expression levels of telomerase component genes and telomerase activity in HCCs. Telomerase is a ribonucleoprotein enzyme composed of a template RNA and several proteins. Recently, three such telomerase component genes have been identified: human telomerase reverse transcriptase (hTERT); human telomerase RNA component (hTERC); and telomerase-associated protein 1 (TEP1). The expression of these components was evaluated in 34 HCCs and 24 non-cancerous liver tissues by reverse transcriptase-polymerase chain reaction (RT-PCR). Expression of hTERT mRNA was detected in most HCCs, but not in the non-cancerous tissues (P<0.01). Expression of hTERC was detected in both HCCs and non-cancerous tissues, but the expression level in HCCs was higher than that in non-cancerous tissues (P<0.01) and tended to increase as histological differentiation became less marked. The expression level of hTERT mRNA correlated with relative telomerase activity (P<0.01). These results suggest that telomerase reactivation during hepatocarcinogenesis might be regulated by only hTERT and an increase in telomerase activity level in tumour progression might be regulated by both hTERT and hTERC.

Pit pattern diagnosis of early colorectal carcinoma by magnifying colonoscopy: clinical and histological implications.

The relation between subclassification of V type pit pattern and histopathologic features, particularly, in regards to the invasion depth, was examined in 75 cases of early colorectal carcinoma. After we classified two grades (VA, VN) of V type pit pattern, we subclassified VN type pit pattern into three subtypes (Grade A, B, and C) according to the degree of appearance of VN pit pattern. V type pit pattern subclassification was diagnosed with use of a magnifying colonoscope. There were 37 VA type lesions, 8 VN.Grade A type, 16 VN.Grade B type, and 14 VN.Grade C type lesions. The incidence of submucosal massive invasion (sm2, sm3) rates was 5 (14%) of the 37 VA type lesions, 3 (38%) of the 8 VN.Grade A type, 15 (94%) of the 16 VN.Grade B type and 14 (100%) of the 14 VN.Grade C type lesions, respectively. The incidence of desmoplastic reaction (++) levels in VN.Grade B and C type lesions was significantly higher than that in VA type lesions (P<0.01), and that in VN.Grade C type lesions was significantly higher than that in VN.Grade A type lesions (P<0.05). The incidence of pit disorder or destruction (+) and (++) levels in VN.Grade B and C type lesions was significantly higher than that in VA type lesions (P<0.01), and that in VN.Grade C type lesions was significantly higher than that in VN.Grade A type lesions (P<0.01). The incidence of high grade carcinoma in VN.Grade B and C type lesions was significantly higher than that in VA type lesions (P<0.01), and that in VN.Grade C type lesions was significantly higher than that in VN.Grade A type lesions (P<0.05). These findings indicate that V type pit pattern subclassification, including our new subtype, is useful for predicting the detail invasion depth of early colorectal carcinoma. These V pit pattern subtypes are based on the degrees of desmoplastic reaction, pit disorder or destruction, and histologic grade of carcinoma.

Combined expression of urokinase-type plasminogen activator and proliferating cell nuclear antigen at the deepest invasive portion correlates with colorectal cancer prognosis.

To examine the relationship among the expression of urokinase-type plasminogen activator (u-PA), invasive/metastatic potential and prognosis of colorectal cancer (CRC), 58 patients with surgically resected advanced CRC were studied. u-PA expression and proliferating cell nuclear antigen labeling index (PCNA-LI) at the deepest invasive portion were examined immunohistochemically. u-PA expression was detected in 37 (63.8%) of 58 lesions. Lesions with liver metastasis showed a significantly (p < 0.01) higher incidence of u-PA expression than those without liver metastasis. Dukes staging also revealed a significant correlation with u-PA expression. The combination of u-PA expression and elevated PCNA-LI at the deepest invasive portion correlated significantly with prognosis. These results indicate that u-PA expression is an important predictor of CRC development and liver metastasis. Furthermore, combined analysis of u-PA expression and PCNA-LI at the deepest invasive portion is very useful in predicting CRC prognosis.

Single carcinoma cells at the deepest invasive portion correlate with metastatic potential of advanced colorectal carcinoma.

The clinical significance of detecting single carcinoma cells (SC) at the deepest invasive portion of a tumor in terms of metastatic potential and prognosis was examined in 57 patients with surgically resected advanced colorectal carcinoma. SC were detected using an immunohistochemical stain for cytokeratin in these sections. The deepest invasive portions of tumors were subclassified by histology into three grades as follows: well-differentiated (W), moderately-well differentiated (Mw; a type that more closely resembles the W tumor), and moderately-poorly differentiated (Mp; more closely resembling poorly differentiated tumor). SC detection was defined positive if more than three single cancer cells with clear cytoplasmic expression of cytokeratin was seen distinct from carcinoma glands and tumor sheets in mid-power (x100) field. SC were detected in 51 (89%) of the 57 carcinomas. There were 5 W or Mw (W/Mw) tumors without SC, 34 W/Mw tumors with SC, 1 Mp tumor without SC, and 17 Mp tumors with SC. W/Mw tumors with SC had a significantly higher (p<0.01) incidence of lymph node metastasis than W/Mw tumors without SC. There was no lesion with lymph node or liver metastasis of W/Mw tumors without SC. SC detection, when combined with histologic subclassification at the deepest invasive portion of a tumor, correlated with prognosis. These results indicate that a combination of the tumor histologic subclassification and SC detection at the deepest invasive portion is a useful predictor of metastatic potential and prognosis in advanced colorectal carcinoma.

Clinical significance of MUC1 and E-cadherin expression, cellular proliferation, and angiogenesis at the deepest invasive portion of colorectal cancer.

We examined MUC1 and E-cadherin expression, cellular proliferation, and tumor vascularization at the deepest invasive portion of colorectal cancer in relation to prognosis. One hundred and ten surgically resected specimens of advanced colorectal carcinoma were studied. E-cadherin and MUC1 expression and Ki-67 labeling index (Ki-67 LI) were examined immunohistochemically at the site of deepest tumor invasion. Tumor vascularization was also examined immunohistochemically using anti-CD34 antibody to determine the microvessel count (MVC). In curative resection, patients with a high Ki-67 LI, reduced E-cadherin expression, MUC1-positive and high MVC lesion showed a significantly poorer prognosis than those with a low Ki-67 LI, E-cadherin normal, MUC1-negative and low MVC lesion, respectively. Furthermore, patients with both a high Ki-67 LI and MVC lesion showed a significantly poorer prognosis than those with other Ki-67 LI and MVC relations. Patients with both a MUC1-positive and E-cadherin reduced lesion showed a significantly poorer prognosis than those with both a MUC1-negative and E-cadherin normal lesion. The significant risk factors in order of poorer prognosis by the multivariate analysis among these factors including routinely used clinicopathologic factors were the high MVC, E-cadherin reduced expression, and lymph node metastasis. These findings indicate a high MVC at the site of deepest tumor invasion to be the most important predictor of colorectal cancer prognosis among the factors studied here.

MUC1 and cathepsin D expression in early colorectal carcinoma showing V type pit pattern.

The relation between MUC1, cathepsin D expression, and histologic features in early colorectal carcinomas (CRCs) with V type pit pattern was examined in 78 patients. We classified V type pit pattern into two grades (VA, VN) and we subclassified the VN type pit pattern into three subtypes (Grade A, B, and C) according to the degree of appearance of VN type pit pattern. At the tumor surface, the status of desmoplastic reaction and pit disorder or destruction were subclassified histologically into three grades (-, +, ++). MUC1 and cathepsin D expression were examined immunohistochemically at a superficial level and at the deepest part of the tumor invasion. MUC1 expression showed a significant correlation with high grade carcinoma, desmoplastic reaction (+) levels in VA type pit pattern (P<0.05), and high grade carcinoma, sm2 and sm3 lesions, desmoplastic reaction (+) and (++) levels, pit disorder or destruction (+) and (++) levels in VN type pit pattern (P<0.05). Cathepsin D expression had a significant correlation with m and sm1 lesions and desmoplastic reaction (-) levels in VN type pit pattern (P<0.05). In VA type pit pattern, a significant correlation between cathepsin D expression and histologic findings was absent. The incidence of MUC1 expression in VN.Grade B and C type pit pattern was significantly higher than that in VA and VN.Grade A type pit pattern (P<0.05). The incidence of cathepsin D expression in VA, VN.Grade A and B type pit pattern was significantly higher than that in VN.Grade C type pit pattern (P<0.05). MUC1 expression (+) or (++) levels at the deepest part of a tumor was identical to that (+) or (++) levels at the superficial part except for one case. Cathepsin D expression at the deepest part of a tumor differed from that at the superficial part. Desmoplastic reaction may be related to MUC1 and cathepsin D expression; however, pit disorder or destruction may be related to only MUC1 expression in V type pit pattern. MUC1 expression at the superficial part of a tumor may be related to expression at the deepest part; however, cathepsin D expression at the superficial part may not be related to expression at the deepest part in submucosal CRCs with V type lesions.

Helicobacter pylori eradication therapy for high-grade mucosa-associated lymphoid tissue lymphomas of the stomach with analysis of p53 and K-ras alteration and microsatellite instability.

Recent studies have shown that 70-80% of low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regress in response to eradication of Helicobacter pylori (H. pylori). However, there are no reports on whether gastric high-grade MALT lymphomas regress after H. pylori eradication. We performed H. pylori eradication therapy in 4 patients with stage I, high-grade MALT lymphoma after obtaining their informed consent. H. pylori infection was observed in all 4 patients. The patients were treated with proton-pump inhibitor-based eradication therapy for 1 or 2 weeks, and then underwent endoscopic examination and biopsy sampling. H. pylori eradication was achieved in all 4 patients. Six months after eradication treatment, 2 patients showed complete regression of the lymphoma and 2 patients showed no change. The 2 patients with non-responding lymphoma were then treated with an additional chemotherapy (CHOP regimen), whereupon the tumors completely regressed. These patients, followed-up at least 18 months after eradication treatment, showed no recurrence. We also examined genetic alteration of the p53 and K-ras genes and microsatellite instability in these high-grade MALT lymphomas. One patient with a tumor that showed no change after H. pylori eradication, had a loss of heterozygosity of the p53 gene. No other genetic alterations were detected among the patients. Our results indicate that the eradication of H. pylori may be effective not only for patients with low-grade MALT lymphoma but also for patients with high-grade MALT lymphoma. The treatment may be efficacious as a first-line therapy for patients with high-grade MALT lymphoma. However, our sample size was limited and further studies are needed to clarify the issue.

Changes in intestinal mucosa above lymph follicles during carcinogenesis in rats. A light and electron microscopic study.

Changes in the intestinal mucosa during carcinogenesis were investigated in 36 rats after weekly s.c. injection of 20 mg dimethylhydrazine/kg bodyweight. More changes were seen in the large than in the small intestine. In the first week, 60% of colonic lymphoid plaques displayed various crypt abscesses and glandular regenerations. These mucosal changes correspond to the glands covering the lymph follicles, in direct contact with lymphoid cells. Beginning in week 8, dysplastic glands developed in these mucosal areas above the lymph follicles. The number of lymphoid plaques with dysplastic glands in the large intestine increased week by week, attaining 75% in week 20. At the end of week 12 the first adenocarcinoma was detected in the cecum by light microscopy, and classified as a poorly differentiated adenocarcinoma with signet ring cells infiltrating the lymph follicles which contained endocrine cells. The majority of adenocarcinomas (10 cases) occurred in week 20. Of these, 7 were localized above the lymphatic plaques in the intestine. Endocrine cells were found in varying numbers in 6 of 10 adenocarcinomas. Three endocrine cell carcinomas, corresponding to human adenocarcinoids or goblet cell carcinoids, developed within the intestinal mucosa; all were identified as poorly differentiated intestinal adenocarcinomas, two of them situated above lymph follicles. These suprafollicular tumors developing from the glandular base, were composed of mucoid cells, endocrine cells, and undifferentiated cells. Microcarcinomas are considered as initial stages of endocrine cell carcinoma.

Gut endocrine cells in rat intestinal-tract carcinoma induced by 1,2-dimethylhydrazine.

Gut endocrine cells in a total of 122 intestinal-tract adenocarcinomas induced in inbred Wistar rats by 1,2-dimethylhydrazine dihydrochloride were examined histologically, ultrastructurally, and immunohistochemically for gastrin, somatostatin, vasoactive-intestinal polypeptide (VIP), and glicentin (enteroglucagon). Of the 122 tumors, argyrophil cells were detected in 42 tumors (34.3%) comprising 15 tumors of the well differentiated type and 27 tumors of the poorly differentiated type, including signet-ring-cell carcinomas. Of the 27 tumors of the poorly differentiated type, 12 were regarded as endocrine-cell carcinomas composed of numerous argyrophil or argentaffin cells and mucus-containing cells. Immunohistochemically, 7 of the 12 tumors had glicentin and two of these seven tumors also had gastrin and argentaffin cells synchronously. None of the tumors showed immunoreactivity for somatostatin and VIP. Nine of the 12 tumors metastasized to the lung, pancreas, liver, mesenterium, omentum, and lymph nodes. The metastatic foci of these tumors were also shown to have glicentin and argentaffin cells. Ultrastructurally, four types of endocrine granule were found in the tumor cells and amphicrine cells containing endocrine granules and mucous granules were noted. These endocrine-cell tumors were assumed to develop from totipotent immature cells of endodermal origin.

Macrophages and T lymphocytes infiltrating the rat mammary carcinoma HH9-cl 14 in progressive and regressive tumor growth. An immunohistological study.

Ascites tumor cells (2 X 10(6] of a DMBA-induced rat mammary adenocarcinoma (HH9-cl 14) were injected s.c. into tumor-free syngeneic female rats and produced a continuously growing solid tumor in all animals of this group. Inoculation of 2 X 10(7) cells induced a first brief period of tumor growth, followed by complete tumor regression from the 2nd until the 5th week after injection. Both the progressive and the regressive tumors were analyzed immunohistologically at different stages with monoclonal antibodies against different T lymphocytes and macrophages. Obviously these cells appear in different quantity and quality, during the hosts immune response. Possible interactions of T lymphocytes and macrophages with tumor cells are discussed.

Induction of carcinoids in the glandular stomach of rats by N-methyl-N'-nitro-N-nitrosoguanidine.

A total of 30 inbred Wistar rats were orally administered 70 microgram/ml solution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 35 weeks and then tap water for the following 20 to 30 weeks. Four of the 20 females and two of ten males developed carcinoids in the glandular stomach, but no metastasis could be found. Carcinoids developed most frequently in the fundic portion along the greater curvature. Histologically, these tumors were medullary anaplastic carcinomas containing two different endocrine cell populations. The first cell type was argentaffin having the electron-dense, somewhat pleomorphic secretory granules (437-810 nm) and the second type was argyrophil having round granules with a dense core and a pale halo (550 nm). None of these tumors showed endocrine immunoactivity for gastrin, somatostatin, insulin, glucagon, and enkephalin. One of these gastric tumors developed into scirrhous carcinoma, but differentiated adenocarcinoma could not be seen in the glandular stomach.

Argyrophil cells in early gastric carcinoma: an immunohistochemical and ultrastructural study.

Eighteen argyrophil cell carcinomas in 101 early gastric carcinomas were explained histologically, ultrastructurally, and immunohistochemically for polypeptides, carcinoembryonic antigen (CEA), lysozyme, and human chorionic gonadotrophin (hCG). Seven of these 18 tumors had gastrin, and two of seven tumors also contained somatostatin. In all of these 18 tumors CEA were demonstrated. Seven had lysozyme and five of seven tumors also contained gastrin; hCG were present in four of the 18 tumors and two of four tumors had gastrin, CA, mucin, and lysozyme simultaneously. Argentaffin cells were found in seven of 18 tumors. Of the above seven tumors containing gastrin, three had argentaffin cells. Ultrastructurally, several types of secretory granules were noted and tumor cells resembling D1- or P cells were present in nine of the 18 tumors. Macroscopically, many of the tumors showed IIc or IIc + III type. Histologically, the 18 tumors consisted of six well differentiated adenocarcinomas and 12 poorly differentiated adenocarcinomas including signet-ring cell carcinoma. These 12 tumors frequently developed in the stomach of young females. In view of our previous investigations, it was suggested that the IIc-type argyrophil cell carcinoma histologically showing poorly differentiated adenocarcinoma may be related to scirrhous carcinoma of the stomach.

Immunohistochemical analysis of nm23 gene product in human gallbladder carcinomas.

The expression of nm23, the product of a candidate suppressor gene for tumour metastasis, was examined immunohistochemically in human gallbladder carcinomas and compared with clinicopathological features. Seventy-eight (72%) of 107 carcinomas expressed nm23 protein regardless of histological type, while non-neoplastic mucosa occasionally showed very weak immunoreactivity to nm23. No obvious correlation was observed between nm23 protein expression and depth of tumour invasion or tumour stage. The expression of nm23 protein was detected in 60% and 74% of the cases with and without lymph node metastasis, respectively, indicating no relationship to metastatic ability. Fifty-eight percent of the cases showed reduction of nm23 immunoreactivity in tumour cells invading the stroma at the border of tumour cell nests compared with cells at the centre of the tumour. Only 7% of the cases showed increased nm23 expression in tumour cells at the border. These results suggest that in gallbladder carcinoma decreased expression of nm23 may not have implications for metastasis but may play a part in local invasion.

Expression of cyclin E in colorectal adenomas and adenocarcinomas: correlation with expression of Ki-67 antigen and p53 protein.

The expression of cyclin E in human colorectal adenomas and adenocarcinomas was examined immunohistochemically to elucidate the role of cyclin E in the colorectal carcinogenesis. The expression of cyclin E was detected in 25% (91/358) of the adenomas and 56% (149/267) of the adenocarcinomas. The incidence of strongly positive cases was significantly higher in the adenocarcinomas (20%) than in the adenomas (5%) (P < 0.01). Among adenomas, a significant correlation was noticed between the expression of cyclin E and the grade of atypia. The incidence of cyclin E expression was significantly higher in the adenocarcinomas without an adenoma component (62%; 104/169) than in those with this component (46%; 45/98) (P < 0.05). Furthermore, the incidence of the cyclin E expression was higher in stages 1 and 2 carcinoma than in stage 0 and stages 3 and 4 carcinoma. The expression of cyclin E was the most prominent in tumors invading the submucosa and muscularis propria. The expression of cyclin E was significantly correlated with the proliferative activity of the tumor cells measured by Ki-67 antigen expression (P < 0.01). It was also correlated with the expression of p53 protein in the tumor cells (P < 0.01). Overexpression of cyclin E and subsequent deregulation of cell cycle may contribute to the development and early progression of the colorectal carcinomas.

B-cell monoclonality in Helicobacter pylori-associated chronic atrophic gastritis.

B-cell monoclonality has been reported not only in gastric lymphoma, but also in 1.3-21% of Helicobacter pylori-associated chronic gastritis (Hp-CG) cases. The aim of this study was to determine the significance of B-cell monoclonality in Hp-CG. We examined 134 gastric biopsy specimens from 99 patients with Hp-CG. The density of Hp, polymorphonuclear neutrophil activity, chronic inflammation, glandular atrophy, and intestinal metaplasia (IM) were scored according to the updated Sydney System. B-cell monoclonality was analyzed for immunoglobulin heavy chain gene rearrangement using polymerase chain reaction amplification. B-cell monoclonality was detected in 6% of informative samples. B-cell monoclonality was found in 18% of the samples from Hp-CG patients with marked glandular atrophy but in none of the samples from Hp-CG patients with none to moderate glandular atrophy. Monoclonality was also detected in 20% of the samples from Hp-CG patients with marked IM, in 11% of the samples from Hp-CG patients with moderate IM, and in none of the samples from Hp-CG patients without IM. Therefore, B-cell monoclonality was significantly more frequent in Hp-CG patients with marked glandular atrophy than in Hp-CG patients with none to moderate atrophy. It was also more significantly frequent in Hp-CG patients with moderate or marked IM than in Hp-CG patients without IM (P < 0.05). Of 35 Hp-CG patients, 26 (74%) had identical B-cell populations in the antrum and the corpus, and all were polyclonal. The remaining nine (26%) Hp-CG patients had B-cell populations that differed in the antrum and the corpus. Four of the nine (44%) showed monoclonal B-cell populations in at least one gastric biopsy specimen. There were no patients with monoclonal B-cell populations in both the antrum and the corpus. These data suggest that glandular atrophy and IM in gastric biopsy specimens may be markers for gastric mucosa-associated lymphoid tissue (MALT) lymphoma-genesis and that multiple gastric biopsy specimens from both the antrum and the corpus may be needed to assess the risk of gastric MALT lymphoma.

Expression of cyclin E in human gastric adenomas and adenocarcinomas: correlation with proliferative activity and p53 status.

The expression of cyclin E in human gastric adenomas and adenocarcinomas was examined immunohistochemically to elucidate the role of cyclin E in stomach carcinogenesis. The expression of cyclin E was detected in 49% (90/182) of the adenomas and 59% (260/439) of the adenocarcinomas. The incidence of strongly positive cases (overexpression of cyclin E) was significantly higher in the adenocarcinomas (29%; 128/439) than in the adenomas (4%; 8/182) (p < 0.01). The incidence of the cyclin E expression showed a tendency to be higher in deeply invasive carcinomas and in the cases with lymph node metastasis, while the incidence did not differ among histological types. The expression of cyclin E was significantly correlated with the proliferative activity of the tumor cells measured by KI-67 antigen expression (p < 0.01). It was also correlated with the abnormal accumulation of p53 protein in the tumor cells (p < 0.01). These results suggest that overexpression of cyclin E and subsequent deregulation of the cell cycle may confer the development and progression of the gastric carcinomas.

Progression of primary biliary cirrhosis after proctocolectomy for ulcerative colitis.

We report a case of progression of primary biliary cirrhosis (PBC) after proctocolectomy for ulcerative colitis. A 43-year-old woman underwent a total proctocolectomy after being diagnosed with ulcerative colitis. In the course of the preoperative investigation, liver function test results were within the normal range. Four months after the proctocolectomy, the patient showed a high level of alkaline phosphatase (2398 IU/l) and a positive anti-mitochondrial antibody titer (>1:160). There were no associated symptoms. A liver biopsy demonstrated expansion of all portal areas by infiltrates of lymphocytes and histiocytes. These appearances indicated chronic biliary disease and were compatible with PBC. The association of PBC and ulcerative colitis is rare. However, a review of the recent literature suggests that PBC and ulcerative colitis may be associated; this combination should be kept in mind.