Yoshimasa Ohtani

Colitis in chronic granulomatous disease resembling Crohn's disease: comparative analysis of CD68-positive cells between two disease entities.

Chronic granulomatous disease (CGD) is an inhe rited illne ss in which the inability of phagocytic granulocyte s to kill catalase -positive bacteria results in repeated severe infections (1). In CGD, granulocyte s show a de ® ciency of the hydroge n peroxide myelope roxidase ± halide antimicrobial system so that inge sted bacte ria that do not form peroxidase and are catalase positive continue to survive within granulocyte s (2). Thus, these bacte ria become disseminated throughout the body, resulting in the formation of multifocal absce sses and granulomas. In addition to infectious complications due to gastrointe stinal obstructive le sions, inte stinal malabsorption and ® stula formation have been reported in CGD (3± 6). We wish to discuss here the histological feature s of a patient with colitis in CGD resembling Crohn’ s disease.

High Apoptotic Activity and Low Epithelial Cell Proliferation With Underexpression of p21WAF1/CIP1 and p27Kip1 of Mucinous Carcinomas of the Colorectum Comparison With Well-Differentiated Type

We comparatively assessed 41 mucinous colorectal carcinomas (MUCs) and 620 non-MUC (well-, moderately, and poorly differentiated adenocarcinoma) cases for clinicopathologic findings; and 41 MUCs and 115 randomly selected non-MUCs also were studied for the following: (1) apoptotic activity and Ki-67 immunoreactivity; (2) immunohistochemical expression of p21(WAF1/CIP1), p27Kip1, p53, and bcl-2; and (3) c-Ki-ras mutations. The rates for lymph node involvement and peritoneal dissemination were higher in MUCs than in non-MUCs. Multivariate analysis showed MUCs to have a worse prognosis than well-differentiated adenocarcinomas. The Ki-67 labeling for MUCs was significantly lower than that for non-MUCs, whereas the apoptotic index was significantly higher than for the well-differentiated type. The labeling for p21(WAF1/CIP1) and p27Kip1 was lower in MUCs (2.7% and 35.3%, respectively) than in well-differentiated adenocarcinomas (4.2% and 48.6%, respectively). MUCs can be considered a different tumor from the well-differentiated type, with a poor prognosis owing to frequent lymph node metastasis and peritoneal dissemination, and characterized by high apoptotic and low proliferative activities associated with low p21(WAF1/CIP1) and p27Kip1 expression.

Apoptosis of colon cancers assessed by in situ DNA nick end-labeling method

Apoptosis in colon cancers was investigated using in situ DNA nick end‐labeling. Seventy‐six colon cancer cases were divided according to hlstologically defined malignant grading, degree of invasion and other pathologic Indicators. The apoptotic labeling index (ALI) was highest in cases with invasion limited to the submucosa, the difference as compared to other stages being statistically significant, while no correlation was noted between ALI and histological type. ALI significantly decreased with lymph node involvement of cancers. In contrast, there appeared to be no link with vessel invasion. ALI was significantly higher in lesions smaller than 2 cm in diameter. These results indicate that apoptosis In colon cancers is more frequent at a relatively early stage when the lesions are small, and suggest that the apoptotic phenomenon may play some role in regulating the size and progression of such tumors.

Low levels of apoptosis and proliferative activity in colorectal villous tumors : Comparison with tubular tumors

In order to clarlfy the cell kinetics of colorectal villous tumors (VT), 21 villous adenomatous areas and 12 carcinomatous areas within villous adenomas were investigated for proliferative activity and apoptosis and compared with a series of 41 tubular tumors (TT), demonstrating elements of intramucosal carcinomas as well as tubular adenomas (so‐called carcinoma in tubular adenoma). Proliferation was estimated in terms of KI‐67 labeling indices and mitotic indices, and apoptosis was assessed by DNA nick‐end labeling to give apoptotic Indices. Apoptotic indices of villous adenomatous and carcinomatous regions were significantly lower than the values for their tubular counterparts. Kl‐67 labeling indices were also significantly lower for adenoma components. Apoptotic indices, Ki‐67 labeling indices and mitotic Indices increased with atypia raised in tubular adenoma components. Correlations of mitotic indices with apoptotic indices, Ki‐67 labeling Indices with apoptotic indices and mitotic Indices with Ki‐67 labeling indices were found for each villous tumor group and tubular tumor group, and the apoptosis and proliferation ratios for villous tumors were relatively low, suggesting a tendency for greater growth due to less cell deletion. Although this is only one of the biological features of villous tumor groups, it might play a major role in generation of malignancy.

An aggressive desmoid tumor in a patient with familial adenomatous polyposis: immunohistochemical findings.

A case of an aggressive desmoid tumor in a patient with familial adenomatous polyposis is described. The lesion rapidly enlarged with compression of adjacent structures including the ureter and small bowel, and the patient died because of small bowel perforation and hydronephrosis 3 years after detection of small desmoid tumors at the time of a prophylactic coloproctectomy for a colon carcinoma. Immunohistochemically, proliferating cell nuclear antigen (PCNA), p21WAF1/CIP1 and cathepsin D indices, but not the bcl-2 index, which were defined as the numbers of immunoreactive tumor cells per 1000 tumor cells, increased in line with tumor progression. The tumor did not show staining for collagen IV, but was characterized by intense staining for basic fibroblast growth factor (bFGF). Accordingly, tumor aggression was related to increases in both cell proliferation and protease activity, as well as an enhanced expression of bFGF. In addition, the desmoid tumor showed deregulation between PCNA and p21WAF1/CIP1 because the normal inverse relation between these two was not apparent.

Brief Case ReportsAn aggressive desmoid tumor in a patient with familial adenomatous polyposis: immunohistochemical findings

A case of an aggressive desmoid tumor in a patient with familial adenomatous polyposis is described. The lesion rapidlyenlarged with compression of adjacent structures including the ureter and small bowel, and the patient died because of small bowel perforation and hydronephrosis 3 years after detection of small desmoid tumors at the time of a prophylactic coloproctectomy for a colon carcinoma. Immunohistochemically, proliferating cell nuclear antigen (PCNA), p21WAF1/CIP1 and cathepsin D indices, but not the bcl-2 index, which were defined as the numbers of immunoreactive tumor cells per 1000 tumor cells, increased in line with tumor progression. The tumor did not show staining for collagen IV, but was characterized by intense staining for basic fibroblast growth factor (bFGF). Accordingly, tumor aggression was related to increases in both cell proliferation and protease activity, as well as an enhanced expression of bFGF. In addition, the desmoid tumor showed deregulation between PCNA and p21WAF1/CIP1 because the normal inverse relation between these two was not apparent.