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Background: Previously, it could be demonstrated that human patients with malignant diseases of various tissues exhibited characteristic and highly significant changes in the serum patterns of immunoglobulin (Ig)G subclasses, consisting of a decrease in IgG1 and an increase in IgG2 relative to total IgG. The aim of the current study was to determine whether this phenomenon was detectable at the level of IgG-producing B lymphocytes., Methods: Using a competitive reverse transcriptase polymerase chain reaction specific to IgG1 and IgG2, the gene expression of these 2 IgG subclasses in peripheral B cells from 10 patients with carcinomas of various sites within the female reproductive tract and 10 healthy controls was quantitatively determined, in parallel with the concentrations of the respective serum proteins., Results: Absolute levels of IgG subclass messenger ribonucleic acid (mRNA) showed a slight but not significant decrease in IgG1 and an increase in IgG2 in patients with gynecologic malignancies. However, the ratio of IgG1 to IgG2 expression showed a highly significant (P < 0.001) decrease in tumor patients compared with healthy controls, and corresponded to the change in the ratio of IgG1 to IgG2 serum proteins., Conclusions: These data suggest that the shifts in the serum patterns of IgG1 and IgG2 observed in patients with gynecologic malignancies are due to irregular biosynthesis of these IgG subclasses at the B-cell level., (Copyright 2000 American Cancer Society.)

Background: Malignant diseases of various origins were previously shown to be associated with a characteristic and highly significant change in the serum pattern of immunoglobulin (Ig)G subclasses, comprised of a decrease in %IgG1 and an increase in %IgG2 relative to and independent of the absolute concentration of total IgG. The goal of the current study was to evaluate this phenomenon as an indirect marker in the primary diagnosis of colorectal carcinoma., Methods: Using affinity chromatography, IgG1, IgG2, and total IgG were determined in 36 patients with colorectal carcinoma of different stages and compared with 162 apparently healthy controls., Results: It was found that: 1) the mean values for %IgG1 and %IgG2 of all carcinoma patients differed significantly from those of the controls; 2) no quantitative association was found with tumor stages, and four of five patients with incipient adenocarcinoma within a polyp exhibited the characteristic shift in IgG subclasses; 3) based on a calculated cutoff, the specificity and sensitivity of %IgG1 to discriminate between controls and carcinoma patients was found to be 88% and 74%, respectively; and 4) a quantitative correlation between individual %IgG1 values and the probability of correct assignment to carcinoma patients or controls was established., Conclusions: The significant decrease in %IgG1 accompanied by an increase in %IgG2 in total serum IgG represents an indirect, tissue nonspecific, and early marker of malignant proliferation that distinguishes colorectal carcinoma patients from healthy controls with a specificity of 88% and sensitivity of 74%.

Background: Malignant diseases of various tissue origin have previously been found to be associated with a characteristic shift in the serum pattern of IgG subclasses, i.e., a highly significant reduction of the percent of IgG1 and an increase of the percentage of IgG2 relative to the total IgG. In the present study we examined the diagnostic performance of this indirect tumor marker in patients with carcinomas of various sites within the female reproductive tract., Methods: Using quantitative affinity chromatography, the percents of IgG1 and IgG2 in the total IgG were determined for 207 patients with carcinoma of the ovary, cervix, or corpus uteri, prior to any treatment. The data were compared with those of 135 age matched healthy females and 52 patients with benign gynecologic diseases., Results: It was found that (1) mean values for the percents of IgG1 and IgG2 of all of the cancer patients differed significantly from those of the patients with benign disease and healthy controls; (2) no differences were noted between carcinomas of the ovary, corpus or cervix uteri; (3) early stages of carcinoma exhibited the effect to the same extent as late stages; (4) the specificity of the percent of IgG1 to discriminate between controls and cancer patients ranged between 90 and 100%, regardless of localization and stage of tumor; and (5) whereas with ovarian cancer CA 125 showed a slightly greater sensitivity, the percent of IgG1 was by far more sensitive than the conventional markers CA 125, TPA, CEA, Ferritin, and SCC to diagnose carcinoma of the cervix and corpus uteri, notably at early stages. Combined analysis of the percent of IgG1 and CA 125 and/or TPA led to an increase in sensitivity with tumors of all three sites., Conclusions: Thus, the determination of the percent of IgG1 by itself and/or in combination with conventional markers may provide relevant information regarding the noninvasive detection of early stages of gynecologic carcinoma.

Sigma S is a measure of the disulfide bonds and free thiol groups of serum immunoglobulin (Ig) G, as determined by the reaction with dithionitrobenzoate. Significant decreases of sigma S previously were detected in malignant compared with benign diseases of various organs. This study shows the application of sigma S for the diagnosis of breast cancer. The following results were obtained. First, 132 patients with benign breast diseases showed a sigma S of 1.48 +/- 0.29 (standard deviation) per mole IgG; this was not different from 1.51 +/- 0.36 found in 182 controls. In contrast, IgG from 198 patients with primary breast carcinoma of all four stages (tumor-node-metastasis system) gave a sigma S of 1.22 +/- 0.29, a significant (P less than 0.0001) decrease of sigma S from benign to malignant breast disease. Second, sigma S values of single Stages I, II, III, and IV, were 1.27 (n = 59), 1.23 (n = 83), 1.19 (n = 35), and 1.10 (n = 21), respectively, each significantly different from sigma S in benign disease and showing a decreasing trend with increasing tumor progress. Differences were significant between Stages I and IV (P less than 0.025) and II and IV (P less than 0.05). Third, 63% of Stage I breast carcinoma patients had sigma S values below a critical threshold of 1.38. This serum positivity rose to 90% in Stage IV. These values exceeded those reported with other tumor markers. The overall power of sigma S to distinguish between benign and malignant breast disease had a specificity of 61% and a sensitivity of 78%. Early stages (I and II) of breast cancer could be distinguished from benign diseases with 64% specificity and 69% sensitivity. Advanced Stage IV could be discriminated from early Stages I and II with 55% specificity and 71% sensitivity. Thus, the analysis of sigma S may significantly contribute to the surveillance of patients with breast cancer.

The authors evaluated suppressed in vitro functions of peripheral blood lymphocytes (PBL) as a possible tool in the early diagnosis of human lymphoma. In 13 of 22 patients with recent onset of various types of nonleukemic lymphomas (Mb. Hodgkin and non-Hodgkin's lymphomas of B-cell and T-cell origin) the mitogen response of PBL against phytohemagglutinin (PHA) and concanavalin A (Con A), as measured by 3H-thymidine (3HTdR) uptake, was found to be significantly suppressed, whereas the response to pokeweed mitogen (PWM) was normal in 18 cases. In parallel, cytofluorimetric analysis was done with PBL after 72 hours in culture with and without PHA, using antibodies against the differentiation antigens: CD3, CD8, CD4, CD19, and CDw14 and the activation antigens: interleukin-2 (IL-2) receptor (IL-2R, CD25), human leukocyte antigen DR (HLA-DR), and transferrin receptor (TR). Compared with healthy controls and patients with other diseases, a significant reduction of the total T-cell blast response, i.e., the percentage of large T-cells bearing activation markers, was found in all lymphoma cases including those with a normal 3HTdR uptake. Furthermore, a pronounced inhibition in the expression of the activation markers Il-2R and TR, but not of HLA-DR, was detected on CD3+ cells in PHA-stimulated PBL of all lymphoma cases. Thus, polyclonal activation combined with activation antigens seems to give more accurate information about the functional defect(s) of PBL in an early state of lymphoma; these parameters may therefore be valuable diagnostically. The abnormal pattern in the expression of T-cell activation antigens after polyclonal stimulation may help in the understanding the cellular immune defects associated with lymphoma.