CA 15-3 in human breast cancer. Comparison with tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA)

CEA, TPA, CA 15-3 were assayed in 238 patients in follow-up for breast cancer after surgery. CA 15-3 showed the best sensitivity and specificity; the predictive value of a positive CA 15-3 test was three times higher than CEA and TPA. No association was found between marker positivity and the number of organs involved by metastases. CA 15-3 positivity was significantly associated with visceral rather than soft tissue recurrences; no significant similar association was observed for CEA and TPA. CA 15-3 serum levels were early predictors of relapse in four out of nine patients within a 6-12 month follow-up period.     

Impact of preoperative CA 15-3 levels in operable breast cancer. Comparison with tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA)

CA 15-3, TPA and CEA were assayed before surgery in 60 patients with breast cancer. A significant association was found between preoperative CA 15-3 levels and some of the most important prognostic factors in breast cancer, such as lymph node status and tumor size. No similar association was discovered for CEA and TPA. Preoperative CA 15-3 levels were also significantly associated with early recurrences of the disease, thus adding useful information to prognosis especially in N+ patients.     

Localization of mucinous-like carcinoma associated antigen (MCA) in breast pathology: comparison with carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA)

The topographic distribution of a mucinous-like cancer antigen (MCA) recognized by a monoclonal antibody b-12 (MAb b-12) was assessed in benign (38) and malignant (66) breast tissues. The reactivity of MAb b-12 showed a good selectivity for breast tissues, reacting both with normal tissues and breast cancer. The degree of MCA expression was evaluated in the various groups of breast pathology adopting quantitative criteria of assessment. With the criteria of evaluation adopted, strong staining was observed in 71.4% breast carcinomas. The most positive reaction was demonstrated in mucinous carcinoma. MCA distribution in breast tissue was compared with the distribution of two other antigens, CEA and TPA. Reactivity of MAb b-12 was higher than the reactivity shown by the anti-CEA and anti-TPA antibodies.     

Tissue polypeptide antigen (TPA) in chronic active hepatitis and mild liver diseases.

Tissue polypeptide antigen (TPA) is a non-specific tumor marker with a broad reactivity. Increases in TPA are also observed in benign liver diseases. We conducted this study to evaluate the usefulness of TPA serum level determination in 15 patients with chronic active hepatitis (CAH) and in 30 patients with mild liver diseases (MLD) diagnosed at the time of evaluation. TPA levels were abnormal in 73.3% of CAH patients and in 40% of MLD patients. CAH patients had significantly higher TPA levels than MLD patients (p = 0.006). There was a significant correlation between TPA and ASAT (r = 0.581 p < 0.00001), suggesting that cytolysis plays an important role in the increase in TPA. A TPA value of twice the normal level will unlikely be due to MLD (specificity 90%). TPA can be used in the clinical characterization of these patients and in the selection of patients for biopsy.     

Distribution of tissue polypeptide antigen (TPA) in normal human tissues: Immunohistochemical study on unfixed, methanol-, ethanol-, and formalin-fixed tissues

The distribution of tissue polypeptide antigen (TPA) was studied in unfixed, methanol-, 95% ethanol-1% acetic acid (EA)-, and formalin-fixed paraffin-embedded sections of all adult human tissues using an indirect immunoperoxidase method. The specific staining patterns were virtually identical in unfixed and alcohol-fixed tissues, but in formalin-fixed tissues this similarity was found only after fixation for up to 24 hr and pretreatment with protease for 15 min. Although prolongation of formalin fixation beyond 48 hr increasingly diminished the TPA reactivity, TPA could still be demonstrated in tissues fixed in formalin for up to 6 months. TPA was found to be a cytoplasmic constituent of almost all adult human duct and cavity lining, simple, and stratified epithelia. TPA was not demonstrated in epidermis, renal proximal convoluted and testicular tubules, basket-like myoepithelial cells, nor in most glandular acini, including hepatocytes and pancreatic acinar cells. The TPA staining was also negative in all non-epithelial tissues, including lymph nodes and bone marrow. The well-defined epithelial distribution and the comparable demonstrability in differently preserved tissues make TPA a useful tool for the identification of cells of epithelial character.     

Antibodies to saline extractable tissue antigen in sera of patients with renal diseases

Multiple serum samples originating from 110 renal allograft recipients were examined against saline extract of normal human kidney by means of double diffusion gel precipitation. Eleven recipients were found to be positive; 99 of 106 sera from these patients were positive. Pretransplantation sera were available from 7 of these recipients and 6 patients were found "positive." The precipitation reaction was composed of one line. Identity reactions were formed between the lines produced by sera from all patients except 1. Sera of patients from end-stage renal disease produced similar reaction; however, only 3 of 234 sera from patients with nonrenal diseases precipitated the kidney extract. None of 154 normal sera were positive. Several positive sera also were positive in complement fixation tests with human kidney extract. Evidence was presented that the antibodies under study combined with a nonorgan-specific but species-restricted tissue antigen. The hypothesis was advanced that these antibodies are autoantibodies formed in response to a sequestered antigen released as a result of tissue damage. Apparently, the antigen is released frequently in immunogenic form from injury to kidney but infrequently from injury to other organs.     

Pancreatic spasmolytic polypeptide (PSP): I. Preparation and initial chemical characterization of a new polypeptide from porcine pancreas

A novel polypeptide, named Pancreatic Spasmolytic Polypeptide (PSP), was discovered in a side-fraction from the purification of porcine insulin. PSP was prepared by two different purification methods based on combinations of precipitations, anion-exchange and cation-exchange chromatography. The highest yield obtained, 52 mg PSP/kg pancreas, indicates that the content of PSP in porcine pancreas is about half the content of insulin. Both preparations appeared to be very pure as judged by basic disc electrophoresis, isoelectric focusing, analytical gel filtration and radioimmunoassays for various polypeptides known to be present in pancreas. The PSP molecule contains 106 amino acids (MW about 11 700). PSP is an acidic (pI 4.4), non-glycosylated protein without free N-terminal amino groups, and with high contents of proline and cystine. The high content of S-S bridges (7 per molecule), an unexpected low apparent MW determined by gel filtration, and a remarkable resistance towards treatment with trypsin and chymotrypsin, point to a compact structure of the PSP molecule.     

Tissue polypeptide antigen (TPA) modifications in hepatic cirrhosis, aggressive chronic hepatitis, persistent chronic hepatitis, and in minimal pathology

A total of 104 patients with various liver diseases were studied. Hepatic biopsy was performed and the AST, ALT and TPA in serum were measured. Higher levels of TPA, AST and ALT were found in CAH and LC, lower in CPH and MHP. High serum TPA values, usually suggesting the possibility of neoplasm, should be considered with attention. A follow-up with periodic TPA assays (in addition to AST and ALT) is suggested in patients with acute hepatitis, in order to predict further possible complications such as CAH and LC.     

Effect of opium smoking on concentrations of carcinoembryonic antigen and tissue polypeptide antigen

Previous studies have related opium and its pyrolysates to the risk of developing certain cancers. The aim of this work was to evaluate the clinical usefulness of determining carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) levels in habitual opium smokers. Serum CEA concentrations were measured in 128 opium smokers and in 44 controls of cigarette only smokers and 47 normal non-smokers by an EIA-based assay. TPA levels were also determined in serum and urine of a subgroup in the study population. The results indicated that serum CEA concentrations are higher in opium smokers than in healthy tobacco smokers (p = 0.004) and non-smokers (p = 0.001). The amount of opium used correlated with the serum CEA level (r = 0.276, p < 0.0001). The mean urine and serum TPA levels of the opium-addicted population were also higher than that of the non-smoking control group, but the differences were not statistically significant. We conclude that opium smoking is associated with elevated serum CEA levels. Therefore, for management of opium users with neoplastic diseases, increased levels of serum CEA should be viewed with caution to avoid misdiagnosis.     

Analysis of sera from breast cancer patients by radioimmunoassays

Summary The antibody reactivity of human breast cancer sera was evaluated by means of radioimmunoassays and established breast cancer cell lines. When tested against the MDA-MB 231 cell line, 30 of 324 sera had detectable antibody reactivity. All the positive sera, however, reacted with other cell lines as well, generally including cultures initiated from sites other than breast cancers, and often including animal cell cultures. In competition radioimmunoassays the positive sera fell into various groups, indicating that a diversity of antigens was being detected. Two patients' sera identified antigens that were expressed on breast cancer cells but that were not expressed on an assortment of other cell types. Sera like these two, which identify potentially important tumor markers, could serve as valuable reagents for the analysis of the tumor-assiciated antigens of human breast cancer cells.     

Phosphohexose isomerase and carcinoembryonic antigen in the sera of patients with primary lung cancer

Phosphohexose isomerase (PHI) and carcinoembryonic antigen (CEA) were measured at the time of diagnosis in 300 patients with lung cancer. Serum levels were high in 75.7% and 53.0% of patients respectively. PHI levels were higher in large cell and small cell carcinomas (p less than 0.001). CEA levels were higher in adenocarcinomas (p less than 0.001). Metastatic carcinomas showed higher levels on PHI and CEA than localized cases. Survival was significantly longer in patients with normal PHI (p less than 0.001) and normal CEA (p less than 0.005) than in cases with elevated markers. The prognostic significance of PHI persisted in the different pathological types and stages, whereas CEA only had prognostic impact in non-small cell cases. Serial PHI determinations were useful for follow-up in 82.4% of cases with initial abnormal values and in 55.4% of cases with a normal value. Serial CEA was useful in 41% of cases with initially high value but in less than 15% of those with baseline normal. We conclude that PHI has prognostic significance independently of pathology and stage, whereas CEA was a prognostic indicator only in non-small cell cases; serial PHI determinations were useful more often than CEA for follow-up.     

Monoclonal antibody to a cancer-specific and drug-responsive hydroquinone (NADH) oxidase from the sera of cancer patients

Monoclonal antibodies were generated in mice to a 34-kDa circulating form of a drug-responsive hydroquinone (NADH) oxidase with a protein disulfide-thiol interchange activity specific to the surface of cancer cells and the sera of cancer patients. Screening used Western blots with purified 34-kDa tNOX from HeLa cells and the sera of cancer patients. Epitopes were sought that inhibited the drug-responsive oxidation of NADH with the sera of cancer patients, but which had no effect on NADH oxidation with the sera of healthy volunteers. Two such antisera were generated. One, designated monoclonal antibody (mAb) 12.1, was characterized extensively. The NADH oxidase activity inhibited by mAb 12.1 also was inhibited by the quinone site inhibitor capsaicin (8-methyl- N-vanillyl-6-noneamide). The inhibition was competitive for the drug-responsive protein disulfide-thiol interchange activity assayed either by restoration of activity to scrambled RNase or by cleavage of a dithiodipyridine substrate, and was uncompetitive for NADH oxidation. Both the mAb 12.1 and the postimmune antisera immunoprecipitated drug-responsive NOX activity and identified the same 34-kDa tNOX protein in the sera of cancer patients that was absent from sera of healthy volunteers, and was utilized as immunogen. Preimmune sera from the same mouse as the postimmune antisera was without effect. Both mouse ascites containing mAb 12.1 and postimmune sera (but not preimmune sera) slowed the growth of human cancer cell lines in culture, but did not affect the growth of non-cancerous cell lines. Immunocytochemical and histochemical findings showed that mAb 12.1 reacted with the surface membranes of human carcinoma cells and tissues.     

Carcinoembryonic antigen, ferritin, tissue polypeptide antigen, and CA15/3 in breast cancer: relationship between carcinoma and normal breast tissue

The study of tumor markers in breast cancer tissue may supply information on the tumor's biological features and its clinical behaviour. Forty-nine primary breast cancer patients are evaluable to date. CEA, ferritin, TPA and CA15/3 were measured with radioimmunometric methods in the cytosol of carcinoma and normal tissue from the same breast. The concentrations of the four markers were higher in the tumor than in normal tissue in 42/49 cases for CEA, 47/49 for ferritin, 42/49 for TPA and in 24/29 for CA15/3. However, an overlap was found between carcinoma and normal tissue levels, particularly for CEA and TPA. We can conclude that the four substances studied may be markers of malignancy in breast carcinoma when non-malignant breast tissue from the same patient is determined at the same time, whereas assays within a single, unknown breast tissue sample may be useful only in the case of ferritin and, partly, CA15/3.     

Elevated growth hormone levels in sera from breast cancer patients

The concentrations of growth hormone (GH) and prolactin (PRL) in the serum of 42 breast cancer patients were determined by radioimmunoassay (RIA). Forty percent of the patients had elevated GH levels while only 17% had elevated PRL levels. These findings suggest a relationship between GH and breast cancer; a weaker correlation exists between PRL and this malignancy. In addition, total lactogens in the serum were measured by a bioassay (BA). The BA/RIA (GH + PRL) ratio was greater in the breast cancer patients than the controls, indicating that variant forms of the hormones with higher than normal biological activity might be present.