In 104 patients with breast cancer, carcinoembryonic antigen (Cea), placental alkaline phosphatase (Plap) and the carbohydrate antigen CA-50 were analysed in serum. Excretion of the modified ...nucleoside, pseudouridine, was analysed in urine. The patients were subdivided in three different clinical stages according to disease manifestations. Levels of Cea and pseudouridine correlated to clinical stage and 58 per cent of the patients with distant metastases had elevated levels of Cea, compared with 36 per cent for pseudouridine. For Plap and CA-50, the levels did not show any clear correlation to clinical stage. Increased activity of Plap correlated strongly to tobacco smoking. A decrease in the level of Cea was observed following radical mastectomy. Increase in Cea levels predicted relapse in 5 out of 14 patients within about 3 to 6 months. In patients with tumor manifestations, elevated Cea levels predicted an inferior prognosis compared to those with ordinary levels.
The free beta-subunit of human chorionic gonadotropin beta is expressed in several nontrophoblastic tumours and this is usually associated with aggressive disease. Little is known about human ...chorionic gonadotropin beta expression in renal cancer. We determined the pretreatment levels of human chorionic gonadotropin beta in serum of patients with renal cell carcinoma, and studied whether elevated levels predicted the clinical outcome. Serum samples were collected before surgery from 177 patients with renal cell carcinoma and from 84 apparently healthy controls. Human chorionic gonadotropin beta in serum was measured by a highly sensitive time-resolved immunofluorometric assay. The prognostic value of human chorionic gonadotropin beta, and of usual clinical and pathological variables was analyzed by the Kaplan-Meier method, the log rank test and Cox multiple hazard regression. The serum concentrations of human chorionic gonadotropin beta were increased in 23% of the renal cell carcinoma patients and they were significantly higher in patients with renal cell carcinoma than in controls (P<0.0001). The concentrations did not correlate with clinical stage and histopathological grade, but patients with increased human chorionic gonadotropin beta levels had significantly shorter survival time than those with levels below the median (cut-off 1.2 pmol l(-1), P=0.0029). In multivariate analysis human chorionic gonadotropin beta, tumour stage and grade were independent prognostic variables. The serum concentration of human chorionic gonadotropin beta is an independent prognostic variable in renal cell carcinoma. The preoperative value of human chorionic gonadotropin beta in serum may be used to identify patents with increased risk of progressive disease.
Urinary excretion of pseudouridine, a modified nucleoside, was assessed in 30 patients with Hodgkin's disease, and 106 patients with non-Hodgkin's lymphoma, classified according to the Kiel system. ...Elevated excretion was found in 47% of 49 patients with high-grade malignant (HGM) lymphoma, and in 37% of 57 with low-grade malignant (LGM) lymphoma, in 13% in Hodgkin's disease, and 3% in 79 reference individuals. The level of pseudouridine excretion correlated with clinical stage in HGM lymphoma (p < 0.0001), but not in LGM lymphoma or Hodgkin's disease (p = 0.086 and 0.36 respectively). Of 28 patients with B-symptoms 71% had elevated excretion, compared to 26% of 108 without B-symptoms (p < 0.0001). Elevated excretion of pseudouridine before therapy was associated with shorter survival time in LGM lymphoma stage II to IV disease, (p = 0.022), and a similar tendency was also observed in HGM lymphoma. Using Cox proportional hazard model, age, malignancy grade, excretion of pseudouridine, and disease stage were identified as independent prognostic factors in non-Hodgkin's lymphoma.
Chromogranin A and neuron-specific enolase (NSE) as neuroendocrine markers were evaluated in 200 patients with renal cell carcinoma, and 15 patients with benign renal cysts. Immunoassays of serum ...levels and immunohistochemical staining of tumour tissue were performed. Serum chromogranin A was elevated in 28 (14%) patients with renal cell carcinoma, but the levels did not differ from those for patients with benign cysts. Serum NSE was elevated in 54 (27%) patients, significantly higher compared with controls (p=0.0002). Serum chromogranin A level was positively correlated to serum creatinine and age, but not to tumour stage or grade. Serum NSE level was positively correlated to tumour stage and grade, but not to serum creatinine or age. Immunohistochemical staining for chromogranin A was positive in 1 of 24 (4%), and for NSE in all 18 (100%) tumours analysed. In a multivariate analysis, tumour stage, grade, and serum NSE, but not chromogranin A, were significant predictors of prognosis.
An increased excretion of modified nucleosides has been observed in patients with malignant lymphomas. Using high performance liquid chromatography, we have determined the concentration of ...pseudouridine in the urine from 48 patients with malignant lymphomas. Elevated excretion of pseudouridine was observed in 50% of patients with histiocytic lymphoma, compared to 33% for patients with lymphocytic lymphoma and 13% for Hodgkin's lymphoma. When the patients were subdivided into clinical stages according to disease manifestation, no correlation could be found between level of excretion and the clinical stage. To estimate the prognostic relevance of pseudouridine excretion before treatment, we compared the levels from patients that were deceased due to lymphoma, with those living free from disease. The median observation time for the patients was 27 months. No prognostic value could be attributed to the initial excretion of pseudouridine.
An increased excretion of pseudouridine, a modified nucleoside derived from degraded transfer ribonucleic acid, has been observed in patients with malignant lymphomas. This paper presents the ...analysis of pseudouridine in the urine from 39 patients with non-Hodgkin's lymphomas before treatment. Using the Kiel classification, 57% of the patients with highly malignant lymphomas had elevated excretion of pseudouridine, compared to 28% of patients with low-grade malignancy, and 4% in healthy adults. Subdividing the patients according to clinical stages, an increase of pseudouridine levels paralleled the disease manifestation. Of patients in clinical stages 3 and 4 with highly malignant lymphomas, 85% had elevated excretion. This observation, in combination with shorter survival seen in a group of 22 patients followed 37-61 months, suggests that elevated excretion of pseudouridine is a negative prognostic factor in non-Hodgkin's lymphomas. The level of pseudouridine in the urine gives useful information in staging and for prognosis.
From 62 patients with bronchogenic carcinoma, carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), placental alkaline phosphatase (PLAP) in serum and pseudouridine, a modified ...nucleoside, were analysed in urine. About 60 per cent of the patients had squamous cell carcinoma, and 20 per cent had small cell carcinoma. The patients were allocated into 3 different clinical stages based upon tumor burden, and the markers were analysed before treatment and thereafter. TPA and PLAP had limited value as biologic markers. For both CEA and pseudouridine the frequency of elevated values increased parallel to clinical stage. Elevated levels of these 2 markers were also correlated to shorter survival.
β2-Microglobulin (β2-M) was analysed in serum of 145 patients with renal cell carcinoma, and serum creatinine <125 μmol/1 by a radioimmunometric method. Forty-nine (34%) patients had serum β2-M ...level≥3.0 mg/1. Of the patients with distal metastases 46% had elevated levels, compared with 19% with stage I disease. Serum β2-M correlated with histopathologic grade; 58% of the patients with poorly differentiated (grade 4) tumours had elevated levels compared with 18% in grade 1-2 tumours. Also tumour cell type was associated with serum β2-M; 52% of the patients with plasmic tumours had elevated levels compared with 6% in the clear cell type. In a univariate prognostic analysis elevated serum β2-M level was inversely correlated with survival time. Using a multivariate analysis the strong prognostic factors were clinical stage and tumour diameter. Weaker factors were age and cell type, whereas the prognostic value of serum β2-M disappeared. However, if tumour cell type was excluded from the analysis, serum β2-M was identified as a prognostic factor.