CEA-containing immune complexes in sera of patients with colorectal and breast cancer--analysis of complexed immunoglobulin classes.

A sandwich enzyme immunoassay was developed to detect circulating immune complexes containing carcinoembryonic antigen (CEA) and immunoglobulin (Ig) G, IgA, or IgM using a nitrocellulose-bound anti-CEA antibody as the solid phase reagent. Elevated levels of CEA-containing circulating immune complexes (CEA-IC) were found in 15.4% of 117 sera from patients with colorectal cancer in a postsurgery follow-up study. Also in 24.5% of 102 sera from patients with breast cancer in different states of disease CEA-IC were found. The predominant Ig determined in CEA-IC of colorectal cancer patients was IgA, followed by IgG and IgM, whereas IgG and IgM were the most frequent Igs in CEA-IC of breast cancer patients. Elevated CEA levels were found in 12.0% of the colorectal cancer patients and in 25.4% of sera from breast cancer patients. No significance for the coincidence of elevated CEA levels and CEA-IC was recorded in all patients sera tested. In sera of patients with disease recurrence, however, both parameters were shown to be elevated (CEA 80.7% and CEA-IC 42.3%). The data presented indicate the detection of CEA-IC as an additional parameter for the identification of patients at increased risk for disease recurrence.

Significance of serum phosphohexose isomerase in gastrointestinal cancer at different stages.

The purpose of this study was to reevaluate the significance of serum PHI in gastrointestinal cancer at histopathologically defined stages prior to primary treatment. A total of 248 patients with malignant tumors of the gastrointestinal tract and a collective of 42 patients with noncancerous diseases were studied. The results are compared with those obtained with the established markers tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA). Phosphohexose isomerase (PHI) revealed an overall diagnostic sensitivity of 69%, combined with a specificity of 74%. The corresponding data for TPA were found to be 73 and 47% while for CEA 26 and 95% respectively were determined. Even in the early stages of colorectal and esophageal carcinoma, PHI showed a sensitivity of about 60%. A continuous rise of PHI serum levels, correlating well with the extent of the tumor disease, could be detected. In contrast to TPA and CEA, PHI assay can be carried out with a minimum of laboratory efforts, in a short time and at low costs. These findings suggest that serum PHI assay is a useful aid for screening of gastrointestinal cancer, especially esophageal and gastric carcinoma, and a reliable marker for treatment control and follow-up.

Determination of complement activating circulating immune complexes and an example for antigen specific immune complex assays.

For the screening of complement activating circulating immune complexes a new fluorescence linked immunosorbent assay was developed. Anti-human C3 or anti-human C4 F(ab')2 fragments were coupled to a nitrocellulose matrix. Nitrocellulose pieces of definite size covered with anti-C3 and anti-C4 were incubated with serum samples or standards for 15 min followed by a reaction with a fluorescence labelled anti-human IgG or anti-human-IgM. The nitrocellulose disks were then washed and the remaining fluorescence was read by a solid-phase fluorometer. The method was standardized by a WHO Tetanus toxoid anti-Tetanus immune complex reference substandard. (This standard and further controls were used to prove the reproducibility of the system.) Patients suffering from chronic inflammatory diseases were compared to healthy controls. The best discrimination between patients and controls was demonstrated by the determination of C3-IgG aggregates, followed by C3-IgM, C4-IgG, and C4-IgM aggregates. The easy performance, the stability of necessary chemical substances, the reliable standardization by a reference standard, and the clear-cut differences between patients and healthy control groups proved this test to be suitable for routine purposes. Furthermore, it could be demonstrated by means of an artificial model immune complex that this system can be expanded--by slight modifications--to antigen-specific CIC-assays. A CEA-anti-CEA CIC test is described as an example of an antigen specific CIC test not limited to complement activating CIC, and the data of 127 patients with colorectal carcinoma are given.