Adenoma with clear cell change of the large intestine.

BACKGROUND AND OBJECTIVES: Clear cell change of the large intestinal neoplasm is rare, and its character remains unclear. We report a case of the large intestinal adenoma with clear cell change with immunohistochemical and molecular studies to investigate whether the clear cell change is associated with a malignant progression of the adenoma. METHODS: We studied the histochemical and immunohistochemical staining characteristics of the tumor by staining with hematoxylin-eosin, periodic acid-Schiff, alcian blue, and by immunostaining using antibodies against carcinoembryonic antigen, epithelial membrane antigen, p53, and Ki-67. The c-K-ras codon 12 point mutations were analyzed using a nonradioactive restriction fragment length polymorphism technique. RESULTS: The tumor was composed of a typical tubular adenoma and a tubular adenoma with clear cytoplasm. The clear cytoplasm was negative by mucin stains. Immunohistochemically p53 was negative in both the components. Labeling index of Ki-67 showed no significant difference between the two components. No codon 12 mutation of c-K-ras gene was observed in both the components. CONCLUSION: These findings suggest that the clear cell change of the tubular adenoma is not associated with a malignant progression in adenoma-carcinoma sequence involving c-K-ras and p53.

Gastric antral vascular ectasia causing severe anemia.

Gastric antral vascular ectasia (GAVE) that caused continuous gastrointestinal bleeding is reported in a 76-year-old woman who had been treated with repeated blood transfusions because of severe anemia. Endoscopic examination was performed and diffuse speckled telangiectasia of the entire antrum was observed. Laboratory data showed SGOT > SGPT, decreased chE level and the increased levels of serum gastrin and ICG at 15 min. Anti-HCV antibody was positive. Image examination revealed splenomegaly. There was no family history of telangiectasia, and no telangiectasia was found in other organs. The diagnosis was established as GAVE with liver cirrhosis. Surgical resection of the distal stomach resulted in termination of the bleeding, and the cirrhotic changes of the surface of the liver were revealed at that time, providing further evidence of liver cirrhosis. Although the pathogenesis of GAVE is unknown, liver cirrhosis and hypergastrinemia are thought to be associated with the condition. Importantly, this condition is a cause of severe gastrointestinal bleeding in elderly patients.

The analysis of internal image-bearing anti-idiotypic monoclonal antibody in relation to carcinoembryonic antigen.

Five anti-Id mAb (Ab2) were prepared from a BALB/c mouse immunized with anti-carcinoembryonic Ag (CEA) mAb MA208 (Ab1) in a syngeneic system. These anti-Id mAb appear to recognize unique idiotopes at the combining site of mAb MA208, because they were specifically reactive with mAb MA208 and showed the inhibitory activity against the binding of mAb MA208 to CEA. These anti-Id mAb were divided into three groups: group 1 (M7-625), group 2 (M7-413, M7-914), and group 3 (M7-049, M7-418), according to the analysis of anti-anti-Id antibodies (Ab3) induced with each anti-Id mAb (Ab2). Anti-anti-Id mAb M7-625 antisera (Ab3) reacted with purified CEA in binding assay and in Western blot analysis, and competed with Ab1 binding to CEA. Furthermore, the binding of anti-Id mAb M7-625 (Ab2) to mAb MA208 (Ab1) was inhibited with CEA, indicating that Ab2 mimicks the structure of the epitope in CEA which was recognized with Ab1. These serologic findings suggest that anti-Id mAb M7-625 carries the internal image of the Ag. According to the amino acid sequences of CDR 1, 2, and 3 of the mAb M7-625 variable region, there exists a homology of amino acid sequences between CDR2 in the H chain (5 amino acids of 10) and CDR3 in the L chain (3 amino acids of 9) of mAb M7-625 and domain III of CEA (545-554).

Detection of xenogeneic anti-idiotypic antibodies specific to murine monoclonal antibody 17-1A in patients with gastrointestinal cancer.

Murine monoclonal antibody (MoAb) 17-1A, which reacts with an adenocarcinoma-associated antigen, has recently been utilized in a phase I clinical trial for patients with gastrointestinal tract cancers in Japan. In order to analyze anti-idiotypic (Id) antibodies to murine MoAb 17-1A in the sera of these cancer patients, we established a simple and specific assay. In a modified sandwich assay, normal mouse sera were utilized for neutralization of rat antimouse immunoglobulin (Ig) antibodies and reduction of their nonspecific effects. When the modified sandwich assay was applied to the sera of patients who had been treated with MoAb 17-1A, anti-Id antibodies were induced in 53% of 13 cancer patients with gastrointestinal cancers at 3-4 weeks after infusion of MoAb.

Induction of antigen-specific immune response with use of anti-idiotypic monoclonal antibodies to anti-carcinoembryonic antigen antibodies.

Anti-idiotypic monoclonal antibodies (MoAbs) were prepared in a syngeneic system against anti-carcinoembryonic antigen (CEA) MoAb 5B3 (IgG1), which reacted with a carbohydrate moiety on CEA, and MoAb MA208 (IgG1), which reacted with a peptide on CEA. Anti-idiotypic MoAb T3-503 and T4-202 recognized the private idiotype of MoAb 5B3; anti-idiotypic MoAb M7-049 and M7-625 did so for MoAb MA208. Idiotype mapping showed that MoAb 5B3 has at least two distinct idiotopes at its combining site and MoAb MA208 also has two. Four different anti-idiotypic MoAbs (Ab2) could induce anti-anti-idiotypic antibodies (Ab3) specific to their respective immunizing anti-idiotypic MoAbs. Anti-anti-idiotypic MoAb M7-625 antiserum (at least a part of the antibodies) have the same reactivity as MoAb MA208, since the serum competed with the binding of MoAb MA208 against CEA and contained the antibody population reactive with purified CEA in immunoblotting assay. These results suggest that anti-idiotypic MoAb M7-625 bears the internal image of the antigen (CEA) and induces the anti-anti-idiotypic antibodies specific to CEA. Therefore, an anti-idiotypic antibody bearing the internal image of a tumor associated antigen might be used as a possible tool for vaccination or immunotherapy against malignant tumors as an antigen specific immunomodulator.

New assay to detect shedding antigen with use of anti-idiotypic monoclonal antibodies.

Anti-idiotypic (Anti-Id) monoclonal antibodies (MoAbs) against anti-carcinoembryonic antigen (CEA) monoclonal antibody 5B3 (IgG1) were prepared and characterized. Five anti-Id MoAbs recognized the private idiotype of MoAb 5B3. Idiotype mapping suggested that MoAb 5B3 had at least three distinct idiotopes at its antigen combining site. Utilizing the inhibition of idiotype-anti-idiotype interaction with use of anti-Id MoAb T4-305 or T4-212, an immunoassay to detect shedding CEA was established. The results of this inhibition assay correlated with those of double determinant immunoassay and inhibition percentages linearly increased in a CEA concentration-dependent manner. Since it requires only one epitope of a given antigen molecule, this assay could be widely used for detection of shedding antigens, including tumor-associated antigens.

Preparation and characterization of monoclonal antibodies specific to synthetic peptide of carcinoembryonic antigen.

Monoclonal antibodies (MAbs) were prepared to a synthetic peptide (PI: 119-140 amino acids) in domain 1 of the carcino-embryonic antigen (CEA) molecule. The majority of the amino acids in peptide PI show a hydrophilic character, and similar sequences are repeated in domains I, II and III of this molecule. These MAbs appear to recognize new epitopes of CEA, since representative conventional MAbs to CEA do not show reactivity to synthetic peptide PI. The resulting MAbs were divided into 2 groups; group 1 (MAb PI-706) reacted with peptide PI, but not with purified CEA preparation, while group 2 (MAb PI-234 and PI-255) reacted with either type of antigen, in the immunoblotting assay using purified CEA and in immunostaining of colonic carcinoma tissues. Furthermore, group-1 MAb PI-706 was reactive to purified CEA after treatment with periodate.