Franco Pavesi

Detection of malignant pleural effusions by tumor marker evaluation

Cytologic examination and determination of tumor markers (PHI, LDH, alpha-1-glycoprotein, alpha-2-HS-glycoprotein, beta 2-microglobulin, ferritin [corrected], sialic acid, IgE, fetoprotein, CEA, beta HCG and beta 1-SP-glycoprotein) were carried out in pleural fluid samples obtained from 70 patients with suspected neoplasia. Tumor markers were also determined in sera. The protein content of all pleural effusions was greater than or equal to 3 g/dl. Patients were grouped according to diagnosis as follows: (a) 42 with neoplastic diseases (7 mesotheliomas and 19 lung, 4 ovarian, 3 breast and 8 miscellaneous cancers), (b) 22 with benign inflammations and (c) 6 with congestive effusions. Of the parameters examined, only CEA and beta-HCG [corrected] gave information that the effusion was probably malignant. Using 6 ng/ml as cut-off for CEA and 10 mIU/ml for beta HCG, the sensitivity was 57.1% and 45.2%, respectively, specificity was 92.8% for both parameters and test efficiency 0.75 and 0.69, respectively. When CEA and beta HCG were considered together sensitivity increased to 73.8% and efficiency to 0.78. CEA and/or beta HCG were positive in the pleural effusions of 19 of the 20 malignant pleural effusions, all with a negative cytologic examination, which subsequently became positive in 8. Because of their high specificity, these two parameters are a useful tool and can be routinely measured to evaluate pleural effusions of dubious origin, even if CEA and beta HCG cannot, on [corrected] their own, define the primary malignancy.

Circulating CA 549 and Other Associated Antigens in Breast Cancer Patients

The new marker CA 549 was determined in the serum of 258 breast cancer patients, classified according to TNM (148 at diagnosis and 110 at relapse), using a RIA method (cut-off: 10 U/ml). CEA, CA 15-3 and MCA were also evaluated. At diagnosis, CA 549 was more sensitive than the other markers, and cut-off values of 11 and 12 U/ml did not significantly reduce sensitivity. No significant correlation existed between the markers, except for CA 15-3 and CA 549 (r = 0.65). A new quantitative approach to the four markers was effected in the relapsed patients: an X value was calculated for each marker by dividing serum concentration by its cut-off. In these patients, grouped according to the area involved, marker sensitivities were similar except in locoregional relapse, where CA 549 and MCA were the most sensitive. From the data obtained, the more defined cut-off and the good specificity, it is suggested that CA 549 be routinely determined in the follow-up of the disease.

Beta-2-Microglobulin as a Tumor Marker in Solid Malignancies

Beta-2-microglobulin (beta 2-MG) and CEA were measured in the sera of 186 cancer patients divided into two groups: at diagnosis (D) and at follow-up (F). Four groups of patients at diagnosis (D-I, D-II, D-III and D-IV according to TNM classification) and two at follow-up (in remission, F-RS, and in relapse, F-RP) were considered. All patients had normal serum creatinine and urea concentrations. beta 2-MG values in D-I were significantly (p less than 0.01) lower than those for D-II and D-III, while in D-IV they overlapped those of group D-I. No significant difference was observed between F-RS and F-RP patients. Patients with serum CEA concentration greater than 100 ng/ml revealed beta 2-MG values close to those of groups D-I and D-IV. In 10% of patients in stage IV or with CEA greater than 100 ng/ml beta 2-MG was lower than the mean value of the healthy population. From data beta 2-MG is probably produced by an aspecific reaction to the tumor and the decrease in advanced stages could express a decreased immunologic response. On the other hand, high serum beta 2-MG in the initial stages of the neoplasia may reflect an elevated cell turnover, while low beta 2-MG during the final stages may be due to a weak expression of the protein by highly undifferentiated cells.

Peptichemio, vincristine, prednisone induction treatment in multiple myeloma.

Twenty-nine patients with multiple myeloma, 16 untreated and 13 relapsing after treatment with melphalan and/or cyclophosphamide, were treated with Peptichemio (PTC), vincristine (VCR) and prednisone (PRD). The treatment was well tolerated and produced rapid resolution of bone pain and improved performance status in symptomatic patients. Rapid and marked monoclonal component reduction (> 50 per cent) was noted in 50 % of previously untreated and 31 % of previously treated patients. The median survival of previously untreated patients was 27 months, 19 months for stage III patients. Four patients resistant to common alkylating agents responded to PTC-VCR-PRD treatment and achieved long remissions (from 18 to 38 months). The therapeutic results suggest that the present combination regimen may be indicated for induction treatment of multiple myeloma patients in an advanced stage of the disease, and for treatment of myeloma patients refractory or resistant to melphalan and/or cyclophosphamide.

Identification of specific plasma proteins determining the agarose gel electrophoresis by the immunosubtraction technique.

The immunosubtraction technique was used to identify the proteins in electrophoretically separated plasma. The technique consists of forcing the plasma through a layer of monospecific antibody purified by electrophoresis; the specific protein is thereby precipitated and is consequently absent from the subsequent electrophoretogram. This technique was successfully applied to the following proteins (in order of distance from the anode): prealbumin, albumin, alpha-lipoproteins, alpha 1-antitrypsin, Gc-globulins, alpha 2-macroglobulin, haptoglobin, fibronectin, transferrin, beta-lipoproteins, C3, fibrinogen. The method may be applied to the study of protein polymorphism.

Tumour associated antigens CA 15.3 and CA 125 in ovarian cancer.

CA 125 and CA 15.3 antigens were determined by enzyme immunoassay in 78 patients with ovarian cancer for a total of 540 determinations. The antigens were also investigated in sera from 100 women with other gynaecological diseases, 82 lung cancer patients and in 39 pleural fluids of varying origin. CA 15.3 reference values were evaluated in 91 healthy women (cut-off: 25 U/ml). CA 15.3 sensitivity at diagnosis (60%) and for detecting relapse (44%) was lower than that of CA 125 (90% and 64,7%, respectively). However, CA 15.3 does not increase with aspecific mesothelial cell reaction and thus it is more specific than CA 125. Combined use of the markers during follow-up improves early detection of relapse (at least one of the two was positive in 79%, of cases). Therefore both CA 15.3 and CA 125 should be routinely determined for the detection and monitoring of ovarian cancer.

Selective bone marrow involvement of lymphoplasmacytic cells secreting monoclonal IgA rheumatoid factor in a patient with Sjögren's syndrome and serum hyperviscosity.

The clinical features and results of serological studies of a patient with Sjögrens syndrome, IgA kappa monoclonal gammopathy, and hyperviscosity syndrome are reported. The novel aspect of this case is the selective localisation to the bone marrow of lymphoplasmacytoid cells secreting IgA kappa morphologically identical to the cells infiltrating the salivary glands. The serum of the patient contained large amounts of immunoglobulin-anti-immunoglobulin immune complexes. By gel filtration chromatography it was shown that the immune complexes formed a peak of molecular weight 680 kilodaltons. The immune complexes were dissociable under acidic conditions. The immunoglobulin with rheumatoid activity was characterised as monoclonal IgA kappa protein. Treatment with plasmapheresis combined with immunosuppressive treatment with cyclophosphamide reduced the serum viscosity with concomitant clinical improvement.

Micropolyspora faeni antigens of three commercial extracts

The protein composition of three commercial extracts of Micropolyspora faeni, produced in U.S.A., England and Italy has been evaluated by agarose gel electrophoresis.By crossed immunoelectrophoresis, ‘tandem’-crossed immunoelectrophoresis and by a modification of this last technique, the antigenic composition and the common antigens of the extracts have been investigated. Hyperimmune rabbit serum and a pool of five human sera with precipitins to Micropolyspora faeni have been used as source of antibody.Different quantity and quality of protein content was observed in the available batches. Different antigenic composition was also observed, not directly related to the different proteins contained therein; three antigens were definitely common to all extracts and two of them represented the major antigens of each extract.Despite the total protein content, the major and common antigens were found in similar concentrations in all three products examined. Therefore, the discrepancies observed in the precipitin reactions using the three commercial Micropolyspora faeni extracts are due to differences in the minor antigen composition of the extracts.