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We analyzed the expression of p21, bcl2, and p53 in normal and different pathologic mucosa of the human colorectum using immunohistochemistry and cold polymerase chain reaction-single strand conformation polymorphism. The topography of normal mucosa showed; bcl2 and p53 expression restricted to basal epithelial cells and p21 expressed only in superficial epithelial cells. This topographic expression was altered in hyperplastic polyps and adenomas. Hyperplastic polyps revealed absence of or weak bcl2 expression and strong p21 expression without topography. In adenomas, whereas bcl2 expression increased and extended to parabasal and superficial dysplastic epithelium, the increase of p21 expression was limited to surface dysplastic epithelium. p53 was weakly expressed throughout the full thickness of dysplastic epithelium. Bcl2 expression in adenomas was stronger than in carcinomas; p53 expression was converse and p21 expression was variable. In carcinomas, this topographic expression was largely abrogated but p53 mutation (36%) was more frequent than in adenomas (2%). In carcinomas, p21 and p53 expression correlated inversely, but there was no relationship with bcl2. These results suggest that there is precisely ordered topographic pattern of p21, bcl2, and wild p53 expression in normal colorectal cells, but this becomes disordered during the early stage of colorectal carcinogenesis.

Castleman's disease represents an atypical lymphoproliferative disorder, infrequently associated with various immunologic abnormalities or subsequent development of malignancy such as Kaposi sarcoma, malignant lymphoma and plasmacytoma. Its clinicopathologic features depend on various etiologic factors such as Kaposi sarcoma herpesvirus (KSHV), oversecretion of IL-6, adhesion molecule and follicular dendritic cell dysplasia, etc. To investigate the relationship of Castleman's disease (CD) and the above factors, we reviewed 22 cases of CD. Four cases of KSHV positive CD were detected, all multicentric, plasma cell type, and these cases displayed prominent vascular proliferation, characteristic 'Kaposi-like lesion'. IL-6 and CD54 positive mononuclear cells were scattered in interfollicular areas of KSHV positive cases. Follicular dendritic cell hyperplasia, vascular proliferation, expression of IL-6 and CD54 did not show any significant difference between solitary vs multicentric type, and plasma cell type vs hyaline vascular type. Our study suggests that KSHV positive CD reveals unique pathologic features, and the probable relationship of KSHV and IL-6 and CD54 is discussed.

A 42-year-old female diagnosed with tuberous sclerosis was found to have multiple polyps in the fundus of stomach. On histologic examination, the lesions were hamartomatous polyps. In tuberous sclerosis, many lesions occur in multiple organs and there are several reports about the frequent association of hamartomatous polyps of the colon. However, gastric manifestation of tuberous sclerosis has not been established probably due to its asymptomatic nature. This is the first report of multiple gastric hamartomatous polyposis in patient with tuberous sclerosis.

Abdominal lymphangiomas are uncommon angiomatous tumor occurring mainly in childhood. This is a retrospective clinicopathologic study of 17 cases of abdominal lymphangioma. The patients included are five children and 12 adults, with a mean age at initial presentation of 30.7 years (age ranges 3-63). The locations of the tumors were mesentery (5), retroperitoneum (4), colon (3), omentum (3), mesocolon (1) and gallbladder (1). Infiltrative growth was more common pattern than entirely circumscribed pattern. Masses were mostly multilocular cysts and contained chyle or serous fluid. On immunohistochemical staining, 16 cases were reactive for either CD31 or factor VIII-related antigen. These fact would suggest that intra-abdominal lymphangiomas simulate the immunohistochemical features of collecting lymphatics. Follow up was possible in 12 cases for 3-50 months (mean 19 months) and only one patient showed local recurrence. Although abdominal lymphangiomas are rare in adulthood and correct preoperative diagnosis is difficult, awareness of such a possibility in adulthood will contribute to make a correct preoperative diagnosis.

Calcification of gastric carcinoma is unusual and most of the reported cases were of the mucinous type. This report describes two cases of papillo-tubular adenocarcinoma of the stomach with psammomatous calcification confined only to the papillary portion. Calcification was so heavy that specimen X-ray was able to clearly delineate its distribution. Microscopically, the calcification was confined to the papillary carcinoma area and was not found in the area of the tubular adenocarcinoma. Polymorphic calcific bodies were found in the supportive stroma of papillae and extrapapillary spaces as concentrically laminated psammoma bodies. They were also found in tumor cells as minute corpuscles. The mechanism of neoplastic mineralization in these cases seemed different from ontogenic calcification of mucinous gastric carcinoma and we postulated the mechanism of psammomatous calcification which is referred as intracellular calcification.

Inflammatory bowel disease (IBD) is commonly associated with arthritic manifestations. They are divided into three clinical categories; peripheral arthritis, spondylitis, and sacroiliitis. To evaluate the incidence of arthritis associated with IBD in Korea, we retrospectively reviewed one hundred and twenty-nine patients with IBD, 77 with ulcerative colitis (UC) and 52 with Crohn's disease (CD). Arthritis occurred in twenty-two patients (17.1%); 15 with UC(19.6%), 7 with CD (13.5%). Patients with arthritis had more active inflammations and all were seronegative except one patient. Peripheral arthritis was found in twenty patients (15.5%) and more common in UC (19.6%) than in CD (9.6%). Joint involvements tended to be monoarticular or pauciarticular, and most frequently developed in the knee and ankle. Spondylitis was diagnosed in one patient (1.6%) who showed HLA B27 positivity. Radiographic sacroiliitis was observed in eight patients (6.2%) who revealed HLA B27 negativity. Both peripheral arthritis and sacroiliitis were found in six patients (4.6%). In CD, arthritis occurred in 20% of the patients with colonic involvement but in none of the patients without colonic involvement. In conclusion, arthritis was frequent in patients with IBD. Peripheral arthritis was more common in patients with UC than CD. All the patients with CD and arthritis had colonic involvement.

This study was designed to demonstrate that differentiation of stomach cancer cells can be modified by microenvironmental change and to look for a method inducing or promoting tumor cell differentiation. To evaluate the biomorphological characterization of tumor cell differentiation in suramin-containing in vitro culture of human stomach cancer cell lines, inverted phase-contrast microscopic examination, analysis of growth curves and BrdU-positive S-phase fraction, immunocytochemical study, radioimmunoassay for CEA, transmission electron microscopic examination, DNA flow cytometry, and heterotransplantation in SCID mice were performed. Suramin inhibited tumor cell growth. Development of intracytoplasmic lumina and intercellular lumina was noted in suramin-containing culture with formation of numerous microvilli and frequent desmosomes. The amount of CEA released by a cell was increased in suramin-containing culture. Suramin inhibited heterotransplantation, and a transplant from suramin-containing culture revealed a much higher degree of differentiation than that from suramin-absent culture. Suramin induced no change in DNA ploidy pattern. Elimination of suramin from the culture medium did not reverse the tumor cell differentiation. Each stomach cancer cell line showed a different degree of responsiveness to suramin. In conclusion, this study shows that suramin inhibits growth of SNU-5 and SNU-16 cells and that suramin induces differentiation of SNU-16 cells.

The stomach is the most frequent site of extranodal lymphoma and primary gastric lymphoma might be distinguished from the nodal lymphoma by its different pathogenesis and prognosis. Based on the Isaacson's classification, clinico-pathologic reviews of 38 resected primary gastric lymphomas were done. Immunohistochemical stainings for PCNA, B and T cell markers, bcl-2 and p53 were performed. Eighteen were of low grade and 20 were of high grade. There were significant differences between low and high graders in the aspect of the size, depth of lesion, gross type, immunophenotype, staining intensity for PCNA, expressions of bcl-2 and p53. The overall 2-year survival rate was 85.3%. Factors with prognostic significance on survival by univariate analyses included immunophenotype, histologic grading and PCNA staining pattern. After multivariate analyses, immunophenotype proved to be a significant factor. We think that the histologic grading by Isaacson's classification and the immunohistochemical stainings performed were useful in pathologic and/or clinical aspects. The excellent survival rate in this study was partly due to the selection of resectable cases. However, earlier diagnosis and appropriate treatment might have contributed to the improved prognosis of gastric lymphoma in recent years.

The persistence of muscle fiber number regardless of size reduction in muscle atrophy has not yet been fully explained. For the mechanism inherent in skeletal muscle tissues for preventing cellular death, the protective function of muscle tissue through transglutaminases has been tested, since the enzyme is responsible for structural stabilization and participates in signal transduction. In the present experiment, hindlimb suspension for two weeks caused a marked muscle atrophy in Wistar female rats. Comparison of muscle weight and histological analysis showed that suspension-induced atrophy in the hindlimb was more prominent in the soleus muscle, comprised mainly of type I fiber than that in the plantaris muscle of type II fibers. The immunohistochemical analysis with antitransglutaminase C antibody (anti TGase C Ab) showed that some atrophic bundles of soleus muscle were positively reacted with the antibody. The anti-TGase C Ab-reactive substances were observed to disappear significantly after endurance exercise, indicating their characteristic atrophy-dependency. The enzymatic analysis of transglutaminase showed the increase in activity in the atrophic soleus muscle tissue, compared with that in the normal or exercise-trained muscle tissues. From these results, the expression of TGase in the atrophic muscle is suggested to be the possible marker for muscle atrophy and its expression is probably related with the protective mechanism of the muscle tissue to prevent further cellular damage in the atrophic process.

The proliferative activity of human gastric carcinoma was measured by means of in vitro incorporation of the thymidine analogue, 5-bromo-2'-deoxyuridine (BrdU), into the newly-synthesized DNA of fresh tumors and immunohistochemical staining of proliferating cell nuclear antigen (PCNA) using avidin-biotin peroxidase method. Eighty-two cases of surgically resected human gastric carcinomas consisting of 18 various histologic types were subjected to study. The mean BrdU labelling index (LI) and PCNA LI were 22.9% and 39.1%, respectively. The correlation between BrdU LI and PCNA LI was statistically significant (correlation coefficient mu = 0.61334, p = 0.0001). We concluded that immunohistochemical staining for PCNA may become a practical method instead of in vitro or in vivo BrdU labeling to assess the proliferation fraction of the gastric cancer patient.

Authors performed an immunohistochemical analysis using monoclonal antibody to p53 protein on 15 cases of benign and malignant phyllodes tumor of the breast along with a review of other conventional clinicopathological parameters to investigate the meaning of p53 expression. The cases were composed of 8 benign and 7 malignant lesions. The pattern of p53 expression showed a statistically significant difference between these benign and malignant lesions (p < 0.005). None of the benign cases expressed p53 whereas 6 out of 7 malignant cases did. Among malignant phyllodes tumors, the pattern of expression was diffuse and strong in two cases while granular and relatively weak in the remaining 4 cases. p53 expression seemed to be a unique feature of malignant phyllodes tumors, thereby, one of the most significant parameters for the differentiation of benign and malignant phyllodes tumors of the breast.

Deposition of basement membrane extracellular matrix is influenced by adjacent tumor cells, and in some cases, the pattern of type IV collagen deposit is characteristic in malignant tumors. In this report, we analyzed the difference in type IV collagen deposition patterns between benign and malignant phyllodes tumors (PTs) of the breast. Of the 15 cases of PTs, 8 cases were benign PTs and 7 cases were malignant PTs. Three cases of other primary sarcomas of the breast (stromal sarcoma, angiosarcoma and osteosarcoma) and 2 cases of fibroadenomas were studied for comparison. The malignant PTs were distinguished from benign ones by increased mitotic figures, cellular atypism, and a higher proliferation index of stromal cells. Immunohistochemical staining against type IV collagen in malignant PTs revealed extensive to moderate deposition of type IV collagen around the small blood vessels in duplicate or multilayering pattern, while benign PTs showed minimal deposition in a single linear pattern. All of the three cases of other sarcomas revealed multilayering or meshwork pattern of type IV collagen around the blood vessels. The deposition of type IV collagen around the blood vessels may reflect the malignant behavior of the stromal tumors of the breast.

The proliferative activity of gastric adenomas from 18 patients (42 endoscopic procedures) was compared with follow-up results. These cases were gastric adenomas proven by follow-up with repeated endoscopic procedures for more than 2 years, or were confirmed as gastric adenocarcinoma thereafter by histopathologic examination. Among the eighteen cases, nine showed carcinoma in the subsequent biopsies (group 1) and the remaining nine did not result in carcinoma (group 2). The proliferating cell nuclear antigen (PCNA) positivity rates of the two groups were significantly different (P < 0.01). The average PCNA positivity in group 1 was 33.1%, while it was 10.0% in group 2. The risk of developing carcinoma increased as the PCNA positivity increased: 0% in the low PCNA positivity group, 41% in the mid-positivity group and 89% in the high positivity group. We concluded that growth fraction could be taken into account as one of the most important prognostic factors for gastric adenoma, and accordingly repeated endoscopic biopsies with close follow-up should be carried out especially in the high PCNA positivity group.

An unusual localization of localized colitis cystica profunda in a 31-year-old man is described. The patient presented as anal bleeding and a protruding mass at the descending colon; the mass was polypoid and was made up of papillary epithelial hyperplasia with downward herniation of glands into the submucosa. Only one similar case involving a descending colon has been reported in the world literature.

Eighty rats out of 233 developed malignant tumors in the stomach and small intestine by administration of 100 micrograms/ml N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water for 28 weeks. Fifteen lesions (30%) among the 50 small intestinal carcinomas showed ossification in the tumor, while none in the sarcomas (12 lesions) or gastric adenocarcinomas (59 lesions) showed ossification. Multifocal heterotopic bone formation was found within stroma in close approximation to the neoplastic glands. The islands of bone trabeculae were covered by osteoblast-like cells, and abundant fibroblasts in loose stroma gathered around the bony islands which enclosed osteocytes in lacunae. Neither osteoclast nor cartilage was identified. In 5 cases, ossification was extensive, which comprised the major portion of the stroma. In contrast, intraluminal calcification without ossified foci were occasionally seen in the gastric carcinoma. Ossification of the intestinal tumors correlated to the degree of mucin content (p < 0.05, chi square with Yates' correction), degree of neutrophilic infiltration (p < 0.05), and size of the tumor (p < 0.1). (The average size of the ossified tumor was 21.5 +/- 4.0 mm, while that of nonossified tumors was 12.5 +/- 1.9 mm). The degree of tumoral necrosis, desmoplasia or depth of invasion did not seem to be related to the ossification of the tumor. The ossification rate of this experimental model was much higher than in human cases. Various histologic alterations, such as mucin leakage, inflammatory cell infiltration, necrosis and/or fibrosis, which might be caused by continuous stimulation of the strong carcinogen, may play some role in the ossification of experimental tumors.

The purpose of this study is to elucidate the participation of Paneth cells in experimentally induced adenocarcinoma of the intestine. The rats were fed with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) dissolved in drinking water ad libitum at a concentration of 100 micrograms/ml for 28 weeks. They were sacrificed 12 weeks after the last MNNG administration. A number of tumor cells containing large eosinophilic granules in their supranuclear cytoplasm (Paneth cells) were observed in about 20% of the experimentally induced adenocarcinoma of the small intestine. The granules were stained positively with Lendrum, periodic acid-Schiff, Masson's trichrome, and Mallory's phosphotungstic acid hematoxylin. Ultrastructurally, the granules were round, osmiophilic, and relatively even in size. We compared the morphologic features of the Paneth cell-containing small intestinal adenocarcinomas (Group I) with those without Paneth cells (Group II). Group I was distinguished from Group II by its better differentiation, larger tumor size and lower incidence of calcification. Although Paneth cells are extremely rare in human gastrointestinal carcinomas, twenty percent of MNNG-induced intestinal carcinomas harbor Paneth cells. The neoplastic Paneth cells in experimental carcinomas may differentiate from uncommitted cells in the deeper portion of the crypt.

To determine the effect of verapamil on experimental duodenal ulcer, pathologic assessment and secretory study were performed in the rats with ulcerogenic dose of cysteamine. The cysteamine increased gastric acid secretion and produced double duodenal ulcers at the proximal protion of the duodenum. Intramuscular injection of verapamil, 3 hours later, produced a significant decreased in gastric acid secretion which lasted at least 4 hours (cysteamine vs. cysteamine+ verapamil; 63.5 +/- 18.4 muEq vs. 25.5 +/- 9.0 muEq during the 1st hour after verapamil administration, 83.1 +/- 24.2 muEq vs. 27.8 +/- 12.3 muEq during the 2nd hour, 110.9 +/- 14.4 muEq vs. 38.5 +/- 25.9 muEq during the 3rd hour, 116.4 +/- 12.1 muEq vs. 40.7 +/- 29.6 muEq during the 4th hour, p less than 0.001). However, cysteamine-induced duodenal ulcers were not alleviated by two doses of intramuscular verapamil administration (4 mg/kg x 2). It is presumed that suppression of gastric acid secretion may not be sufficient to reduce cysteamine-induced duodenal ulcer formation or that verapamil itself may have aggresive effects against duodenum. To illucidate the exact role of verapamil in cysteamine-induced duodenal ulcer, further studies would be needed.