Serum CEA and CA 15-3 as prognostic factors in primary breast cancer.

In the present study, we investigated the association of the serum levels of the tumour markers carcinoembryonic antigen and cancer antigen 15-3 with disease free survival and death from disease in 1046 women with breast cancer without metastases at the time of primary diagnosis in relation to age and the established prognostic factors tumour size, lymph node status, histological grading and hormone receptor status. We found that elevated pre-operative serum marker values were correlated with early relapse (cancer antigen 15-3; P=0.0003) and death from disease (carcinoembryonic antigen, cancer antigen 15-3; P=0.0001 both) in univariate analyses. By comparing pre- and post-operative values we found a decline in values post-surgery. In those patients where marker levels of carcinoembryonic antigen decreased more than 33%, a significantly higher risk for relapse and death from disease (both P=0.0001) in univariate analyses was observed. In multivariate analysis this decrease of carcinoembryonic antigen proved to be an independent prognostic factor. The results for cancer antigen 15-3 were comparable to carcinoembryonic antigen in univariate analyses but showed no significance in multivariate analysis. In this study the post-operative decrease of the serum tumour marker carcinoembryonic antigen was a strong independent prognostic factor for disease free survival and death from disease in breast cancer patients.

Tumour markers CEA and CA 15-3 as Prognostic factors in breast cancer--univariate and multivariate analysis.

Tumour markers are putative prognostic indicators for patients with breast cancer, but have not been elevated independently by multivariate analysis in a large patient number. In 550 patients with breast cancer without known metastases the levels of the serum tumour markers CEA und CA 15-3 were determined preoperatively and during follow-up. The prognostic relevance of these markers for recurrence (n = 128/487) and death of disease (n = 55/550) was evaluated in relation to established prognostic factors. In univariate analysis tumour size, lymph nodes, histological grading, age, hormone receptors, preoperative value of CEA (cut-off 2 ng/mL) and CA 15-3 (cut-off 25 U/mL) and their decrease of more than 33% within seven months after operation were significant for relapse. The results for death of disease were similar except for age. In multivariate analysis tumour size, lymph nodes and decrease of CEA > 33% (p < 0.001) were independent prognostic factors for recurrence. For overall survival tumour size, lymph nodes, histological grading and preoperative levels of CEA > or = 2 ng/mL (p = 0.038) and of CA 15-3 > or = 25 U/mL (p = 0.007) were independent prognostic factors. Pre- and postoperative values of the tumour markers CEA und CA 15-3 are strong independent prognostic factors for relapse and survival in breast cancer patients.

Alkaline phosphatase isoenzymes in detection and follow up of breast cancer metastases.

Alkaline phosphatase isoenzymes in bone and liver metastases of breast cancer were determined in 637 patients and during follow up in 116 patients, by agarose gel electrophoresis. The activity of total alkaline phosphatase, gamma glutamyl transferase, CEA and CA 15-3 was also determined. The sensitivity of bone alkaline phosphatase in bone metastases detection was 39%, of electrophoresis (total alkaline phosphatase and specific isoenzymes) 48% and of enzymes and tumor markers together 85% (n = 62). For liver metastases gamma glutamyl transferase had the best sensitivity (100%, n = 19). Even though positive predictive value was only 6%, the sensitivity of liver alkaline phosphatase was 58% and of electrophoresis 94%. The determination of alkaline phosphatase isoenzymes is a non-invasive, in-expensive, reproductable and rapid method to detect progressive disease in breast cancer, especially in combination with the tumor markers CA 15-3 and CEA.

Prognostic value of preoperative serum levels of CEA, CA 19-9 and CA 72-4 in gastric carcinoma.

UNLABELLED: We studied the relevance of CEA, CA 19-9, CA 72-4 and the common classical prognostic factors (age, sex, tumor infiltration, N-classification, staging, grading and Lauren classification) in gastric carcinoma. PATIENTS AND METHODS: Survival function estimates were calculated according the method to Kaplan-Meier. The patients were separated into two groups according to preoperative marker levels. Fixing specificity at 100% for healthy people, cut off levels were calculated. Survival curve differences were assessed using the log-rank-test. Multivariate Cox proportional hazards regression analysis was performed. The mantel-Haenszel method was used to assess the 2-year survival rate of patients with gastric carcinoma and high versus low levels of tumor-associated antigens adjusted to tumor stages. The study was performed on the frozen sera (stored at -80 degrees C) of 103 patients with histologically proven gastric carcinoma. RESULTS: The tumor stage (log-rank chi-square = 55.9; P < 0.0001) represents the best prognostic factor besides preoperative values of CA 19-9 (log-rank chi-square = 13.9; P < 0.001) and CEA (log-rank chi-square = 12.2; P < 0.001). CA 72.4 shows a log-rank chi-square of 6.9 (P < 0.01). We found no statistically significant correlation between survival and sex, tumor grade and Lauren classification. The importance of different parameters in providing additional prognostic information was evaluated by multivariate analysis. Only patients after curative surgical intervention (n = 55, R0) were considered. Cox proportional hazards regression analysis yielded an adjusted relative risk of 2.4 in patients with a preoperative CEA concentrations > or = 4 ng/mL vs. < 4 ng/mL, of 2.8 in patients with a preoperative CA 19-9 concentration > or = 60 U/mL vs. < CA 19-9 and of 1.8 for stage III/IV vs. stage I/II (P < 0.05). For CEA the 2-year survival rates in the group of patients with preoperative serum concentrations > or = 4 ng/mL versus < 4 ng/mL and stadium III/IV were 14% versus 29% and in stadium I/II 50% versus 83% (P < 0.05). For CA 19-9 the 2-years survival rates in the group of patients with preoperative serum concentrations > or = 60 U/mL versus < 60 U/mL and stadium III/IV were 14% versus 28% and in stadium I/II 40% versus 83% (P < 0.05). CONCLUSION: The postoperative R-classification and the tumor stage represent the best prognostic information besides the preoperative values of CA 19-9 or CEA, respectively. The predictive information provided by preoperative CEA and CA 19-9 serum levels is additional to that obtained from other factors investigated.

Preoperative serum levels of CEA and CA 19-9 and their prognostic significance in colorectal carcinoma.

UNLABELLED: The prognostic information provided by preoperative serum CEA, CA 19-9 antigen assays as compared with the classical prognostic factors (age, sex, tumor infiltration, tumor stage (Dukes') and R-classification) in 495 patients with colorectal carcinoma was analysed. PATIENTS AND METHODS: Survival function estimates were calculated according to Kaplan-Meier. The patients were separated into two groups according to the preoperative marker levels. Fixing specificity at 100% for healthy people, cut off levels were calculated. Survival curve differences were assessed using the log-rank-test. Multivariate Cox's proportional hazard regression analysis was performed. The Mantel-Haenszel method was used to assess the survival rate of patients with colorectal carcinoma and high versus low levels of tumor-associated antigens according to tumor stages. The study was performed on the frozen sera (stored at -80 degrees C) of 495 patients with histologically proven colorectal carcinoma. RESULTS: The Dukes' stages (log-rank chi-square = 231.9; P < 0.0001) represent the best prognostic factor besides the preoperative values of CA 19-9 (log-rank chi-square = 162.5). CEA shows a log-rank chi-square of 71.4. Thus, CEA and CA 19-9 can be used to discriminate two groups of patients with significantly different survival times (P < 0.0001). The importance of different parameters in providing additional prognostic information was evaluated by multivariate analysis (Cox's model). Estimated relative risks of death adjusted for tumor stage were 5.5 for Dukes' stage A versus Dukes' stage B/C and Dukes' stage B/C versus Dukes' stage D, respectively and an increasing relative risk of 27.5 for Dukes' stage A versus Dukes' stage D (P < 0.001). The relative risk for preoperative CA 19-9 serum concentrations (> or = 60 U/mL versus < 60 U/mL) was 2.3 (P < 0.001) for preoperative CEA concentrations (> or = 4 ng/mL versus < 4 ng/mL) 1.4 (P < 0.07). For CEA the 2-years survival rates in the group of patients with preoperative serum concentrations > or = 4 ng/mL versus < 4 ng/mL and Dukes' stage D were 16% versus 38%, in Dukes' stage B/C 73% versus 91% and in Dukes' stage A 100% versus 98%. For CA 19-9 the 2-years survival rates in the group of patients with preoperative serum concentrations > or = 60 U/mL versus < 60 U/mL and Dukes' stage D were 10% versus 39%, in Dukes' stage B/C 58% versus 87%. In the group of patients with Dukes' stage A with serum levels > or = 60 U/mL a 2-year survival rate of 100% was found. In the corresponding group only one patient exists. CONCLUSION: The postoperative Dukes' classification provides the best prognostic information besides the preoperative values of CA 19-9. The predictive information provided by the preoperative CA 19-9 serum level is additional to that obtained from the other factors investigated.

Significance of tumor marker determinations in the primary therapy of ovarian cancer.

In 296 patients with primary ovarian cancer the sensitivity and specificity of CA125 and carcinoembryonic antigen (CEA) were determined. High CA125 values can be found in serous cystadenocarcinomas, CA125 can also be detected in patients with mucinous carcinomas. Only in cases negative for CA125 should other tumor markers be determined. As a second choice CA72-4 is proposed, since because of its low sensitivity of only 9% CEA should no longer be regularly determined in ovarian cancer. Preoperatively determined CA125 values show no prognostic significance in primary ovarian cancer. The means of CA125 half life in primary therapy demonstrated prognostic significance, and therefore patients with a worse prognostic outcome can be spared the adverse side effects of ineffective chemotherapy.

Prognostic significance of squamous cell carcinoma (SCC) antigen in primary advanced and recurrent cervical carcinoma.

Between January 1986 and June 1992 56 patients with cervical carcinoma were treated with cytostatic drugs in our department. In all patients showing primary response to therapy, the SCC and CEA levels fell rapidly to normal after one or two cycles. In contrast, clinical remission was not obtained in those patients with levels which remained high or rose again following an initial decrease. Using tumor markers, treatment can be individualized so that, cases of therapy failure or further tumor progression can be detected early and the patient can be spared the severe side effects of treatment.

Prognostic significance of CA125 in patients with ovarian cancer and secondary debulking surgery.

Prognostic outcome of patients with bulky disease after primary surgery in ovarian cancer remains extremely poor. One possible approach to achieve prolonged survival is secondary debulking surgery, but only in those patients without residual tumor after the second surgery. In 79 patients with secondary debulking surgery preoperative CA125 values were determined. In 52% of the patients with CA125 values below 35 U/ml a tumor free situation could be achieved at secondary debulking. In contrast, the percentage of patients macroscopically free of disease with levels above 35 U/ml was only 22%. Furthermore, there was a significant difference in survival time depending on CA125 values at the time of secondary debulking. Patients with levels below 35 U/ml survived 49 months, women with values above 35 U/ml survived only 30 months respectively. In conclusion, CA125 is an important prognostic tool for predicting a tumor free situation at secondary debulking surgery. In patients with values above 35 U/ml secondary debulking should be indicated restrictively, even if other preoperative diagnostic tools would predict a tumor free situation after secondary cytoreductive surgery.

The ratio of free to total prostate specific antigen: an advantageous addition in the differential diagnosis of benign hyperplasia and cancer of the prostate?

UNLABELLED: This study examined the clinical relevance of the determination of free PSA (f-PSA) in addition to total PSA (t-PSA). PATIENTS AND METHODS: Both total PSA- and free PSA-values of frozen sera obtained pretherapeutically from 80 patients with carcinoma (PC) and 171 patients with benign hyperplasia of the prostate (BPH) were analysed by means of PSA IRMA and FREE PSA IRMA (IMMUNOCORP/IBL). RESULTS: At 95% specificity (true negative test results), a cut-off value of 16.8 [micrograms/L] was obtained for total PSA (9 patients with BPH [5%] were above this value). For this cut-off value we calculated a sensitivity (true positive test results) of 41%. Using the same criteria for the ratio Q = f-PSA:t-PSA a cut-off of 0.083 was found again at a specificity of 95%. In a second step only patients with total PSA values below the cut-off level of 16.8 [micrograms/L]) were considered. Of these patients 11 of 160 with BPH (missing values = 1) and 13 of 33 with PC (missing values = 2) were below the above mentioned ratio (Q = 0.083). Considering both steps (total PSA and Q) 46 patients with PC were detected correctly and 20 patients with BPH would have been biopsied unnecessarily (positive biopsy rate: 70%). CONCLUSION: High total PSA levels are a very good indicator for the presence of prostate cancer. There is still concern to improve the differentiation between the diagnosis between BPH and PC, when an intermediate or low value (< or = 95% specificity) is observed. The determination of Q is only useful in this range and might be helpful for the clinician's decision to apply or avoid biopsy.

Screening for prostatic carcinoma with prostate specific antigen.

The usefulness of prostate specific antigen (PSA) in screening for prostatic carcinoma was studied in 262 inpatients of the department of internal medicine. All patients underwent a rectal digital examination and determination of PSA by the Tandem-E method (Hybritech). The plan was to perform biopsies if there were suspicious findings on the rectal examination or if the PSA value was more than 10 ng/ml. The PSA values were < or = 4 ng/ml in 219 patients (83.6%), > 4 to 10 ng/ml in 27 patients (10.3%) and > 10 ng/ml in 16 men (6.1%). In consideration of the severity of disease which limited life expectancy we did not perform a biopsy on 37.5% of the patients with PSA > 10 ng/ml. 7 patients with prostatic carcinoma were found. Their PSA values varied between 11.2 and 875 ng/ml. The cancer detection rate was highest for the combination of a suspicious rectal examination and a PSA value > 10 ng/ml (70%).

CA125 based diagnosis and therapy in recurrent ovarian cancer.

Approximately 85% of patients with advanced ovarian cancer will experience recurrence of the disease. In 311 patients CA125 serum levels were determined at follow up investigation in our department. A sensitivity of 92% and specificity of 89% were calculated. Reflecting the further course of disease, specificity could be increased up to 97%. Using 25 U/ml/month as the upper limit of grade of CA125 increase, a 100% specificity for detecting recurrence could be achieved. In conclusion, recurrence diagnosis and even therapy should be started in cases of either significantly raised CA125 levels or elevated grade of CA125 increase.

Serum thymidine kinase in non-Hodgkin lymphomas with special regard to multiple myeloma.

S-TK (Serum thymidine kinase) levels were determined by means of a radioenzyme assay (REA). In 95% of healthy controls (n = 97), S-TK values were below 8.5 U/L. In patients with monoclonal gammopathies of undetermined significance (MGUS) (n = 27) or polyclonal gammopathies (n = 45) the cut off was 10.3 U/L respectively 25 U/L. Patients with viral disease (n = 16), especially infections with Epstein-Barr virus, Hepatitis-virus and HIV, had elevated S-TK values of up to 215 U/L. In 95 patients with multiple myeloma (MM) and 103 patients with other various non-Hodgkin lymphomas (NHL) S-TK levels were investigated. With regard to monoclonal gammopathies, MGUS had lower S-TK than MM patients (p < 0.05) and patients with stage I MM according to Durie and Salmon had S-TK levels significantly lower than those with more advanced stages (p < 0.01). There was a correlation between S-TK and plasma cell labeling index (r = 0.56, p < 0.001). Patients with chronic lymphocytic leukemia showed significantly higher S-TK levels in the RAI stages 3 and 4 than in stages 1 and 2 (p < 0.01). In cases of other malignant NHL in progression sensitivities of S-TK were found to be: immunocytoma 36%, centrocytic/centroblastic-centrocytic lymphoma 54% and high-grade NHL 40% (cut off defined on lymphomas in remission). S-TK levels varied in MM according to the course of disease and response to therapy decreasing at remission and increasing again at relapse. Analogous variations were found in the other NHL. After two years, 83% of patients with a pretreatment S-TK of < 10 U/L and 47% of the patients with a S-TK of > or = 10 U/L were still alive. S-TK proved to be a highly significant prognostic indicator for MM patients (log-rank and Wilcoxon: p < 0.0001). In the other NHL patients with a S-TK level greater than 10 U/L had a median follow-up of only 7 months. NHL patients with lower S-TK levels did not yet reach the median survival time (log-rank and Wilcoxon. p < 0.005). Our results suggest that the determination of S-TK may help to monitor the clinical course of NHL during therapy and predict the prognosis of NHL.

Evaluation of serum neural cell adhesion molecule as a prognostic marker in multiple myeloma.

Serum neural cell adhesion molecule (NCAM), a possible prognostic marker for multiple myeloma (MM), was determined by means of an enzyme immunoassay, which showed good linearity and high precision. In 95% of healthy controls (n = 70), NCAM values were below 18.7 U/mL. In patients with monoclorlal gammopathies of undetermined significance (MGUS) (n = 31) or polyclonal gammopathies (n = 53) the cut off was 23.1 U/mL. MM in active stage (n = 52) showed significantly higher NCAM levels (p < 0.001) than in asymptomatic stage (n = 44). In active myeloma the sensitivity of serum markers were found to be: NCAM 40%, beta 2-microglobulin beta 2-M) 52% and serum thymidine-kinase (S-TK) 41% (cut off defined on MGUS). The combined sensitivities ranged between 55 and 60% (NCAM+ beta 2-M, beta 2-M+S-TK, NCAM+S-TK). No correlation with beta 2-M or S-TK could be demonstrated. However, NCAM values were correlated with the concentration of monoclonal immunoglobulin (IgG-paraprotein: r = 0.45; IgA-paraprotein: r = 0.58). In the follow-up of patients with myeloma, NCAM values decreased in response to chemotherapy and were low in smouldering myeloma. But in three patients with progression NCAM did not reflect the tumor activity. At the time of censor, 80% of patients (n = 80) with a pre-treatment NCAM of < 18.5 U/mL and 61% of patients with a NCAM of > 18.5 U/mL were still alive. NCAM showed a low prognostic significance (log-rank: p < 0.07). Seven of ten myeloma patients with CD56 expression on plasma cell surface, which was examined by flow cytometry, displayed a high concentration of NCAM in serum. All other non-Hodgkin's lymphomas (21 immunocytoma, 27 chronic lymphocytic leukemia, 16 centrocytic/centroblastic-centrocytic lymphoma, 24 high-grade lymphoma) had low NCAM concentrations in serum and did not significantly vary in follow-up. In conclusion, serum NCAM could be a marker for the staging and monitoring of MM. However, it seems, that NCAM did not provide additional prognostic information relating to beta 2-M, S-TK or paraprotein.

Is free prostate-specific antigen helpful in the differential diagnosis of benign hyperplasia and cancer of the prostate?

PURPOSE: We studied the clinical relevance of the determination of free prostate-specific antigen (f-PSA) in addition to total PSA (t-PSA). METHODS: Both t-PSA and f-PSA values of frozen sera obtained pretherapeutically from 80 patients with prostate carcinoma (PC) and 171 patients with benign hyperplasia of the prostate (BPH) were analyzed by means of the Tandem-E PSA and Tandem-R f-PSA immunoassays (Hybritech, San Diego, Calif.). RESULTS: At 95% specificity, a cutoff value of 15.7 micrograms/l was obtained for t-PSA [9 patients with BPH (5%) were above this value]. For this cutoff value, we calculated a sensitivity of 50% (40 patients with PC were above this value). Using the same criteria for the ratio (Q) f-PSA:t-PSA a cutoff of 0.086 was found again at a specificity of 95%. In a second step, only patients with t-PSA values below the cutoff level of 15.7 micrograms/l were considered. Out of these patients, 6 of 156 with BPH (missing values = 6) and 11 of 40 with PC were below the above-mentioned ratio (Q = 0.086). Therefore, sensitivity was 28% for this subgroup. Considering both steps (t-PSA and Q) 51 patients with PC were detected correctly and 15 patients with BPH would have undergone biopsy unnecessarily (positive biopsy rate: 77%). CONCLUSIONS: High t-PSA levels are very good indicators for the presence of PC. There is still concern for improving the differentiation between BPH and PC, when an intermediate or low value (< or = 95% specificity) is observed. The determination of Q is only useful in this range and is helpful for the clinician's decision whether to apply or avoid biopsy.

Alpha 1-antichymotrypsin-PSA (ACT-PSA): a useful marker in the differential diagnosis of benign hyperplasia and cancer of the prostate?

UNLABELLED: This study examined the clinical relevance of the determination of alpha 1-antichymotrypsin complexed PSA (ACT-PSA) in addition to total PSA antigen (t-PSA). PATIENTS AND METHODS: Both total PSA- and ACT-PSA-values of frozen sera obtained pretherapeutically from 93 patients with carcinoma (PC) and 132 patients with benign hyperplasia of the prostate (BPH) were analyzed by means of PSA sandwich-ELISA (Dianova GmbH) and ACT-PSA sandwich-ELISA (Dianova GmbH). RESULTS: At 95% specificity (true negative test results), a cutoff value of 18.9 [micrograms/L] was obtained for total PSA (7 patients with BPH [5%] were above this value). For this cutoff value we calculated a sensitivity (true positive test results) of 41%. Using the same criteria for the ratio Q = ACT-PSA: t-PSA (percentage of ACT-PSA) a cutoff of 6.0 was found again at a specificity of 95%. In a second step only patients with total PSA values below the cutoff level of 18.9 [micrograms/L]) were considered. Out of these patients 119 of 125 with BPH and 3 of 54 with PC were below the above mentioned ratio (Q = 6.0). Considering both steps (total PSA and Q) 42 patients with PC were detected correctly and 15 patients with BPH would have been biopsied unnecessarily. CONCLUSION: High total PSA levels are a very good indicator for the presence of prostate cancer. There is still concern to improve the differentiation of the diagnosis between BPH and PC, when an intermediate or low value (< or = 95% specificity) is observed. The determination of Q = ACT-PSA: t-PSA is not to be recommended because it might not be helpful for the clinicians decision to perform biopsy.

Total and free PSA: a methodical and clinical evaluation of five assays.

UNLABELLED: We studied the methodical and clinical relevance of five determination assays for free PSA (f-PSA) in addition to the corresponding total PSA antigen (t-PSA). METHODS: Both the total PSA- and free-PSA-values of frozen sera obtained pretherapeutically from 80 patients with carcinoma (PC) and 171 patients with benign hyperplasia of the prostate (BPH) were analysed by means of Enzymun-Test PSA/BM, PSA-RIACT/ CIS, CanAg PSA EIA/ Dia, Tandem-E PSA/Hyb, PSA IRMA/ IBL and Enzymun-Test PSA free/BM, F PSA-RIACT/CIS, CanAg Anti Free PSA/Dia, Tandem-R free PSA/Hyb, FREE PSA IRMA/IBL. RESULTS: The coefficient of correlation between Hybritech PSA assay and the other assays was determined in patients with benign and malignant prostatic diseases. There was a strong overall correlation with all assays measuring total or free PSA, respectively. A satisfying correlation is also shown using a limited scale up to 50 ng/mL for total PSA and 5 ng/mL for free PSA. At 95% specificity sensitivities of total PSA between 40% and 50% of the ratio (Q) = free PSA/total PSA between 4% and 28% were calculated. In a second step only patients with total PSA values below the cutoff level of 16.5 [micrograms/l] (BM), 13.9 [micrograms/l] (CIS), 14.7 [micrograms/l] (Dia), 15.7 [micrograms/l] (Hyb) and 16.8 [micrograms/l] (IBL) were considered. Using the BM assays, of these patients 9 of 162 with BPH and 14 of 47 with PC [CIS: 14 of 162 with BPH and 4 of 48 with PC/Dia: 13 of 162 with BPH and 11 of 48 with PC/Hyb: 6 of 156 with BPH (missing values = 6) and 11 of 40 with PC/IBL: 11 of 160 with BPH (missing values = 1) and 13 of 33 with PC (missing values = 2)] were below the ratio Q = free PSA/total PSA. Considering both steps (total PSA and Q) using the BM assay 47 patlents with PC were detected correctly and 18 patients with BPH would have been biopsied unnecessarily (positive biopsy rate = pos. br.: 72%) [CIS: 38 patients with PC and 23 patients with BPH (pos. br.: 62%)/Dia: 43 patients with PC and 22 patients with BPH (pos. br.: 66%)/Hyb: 51 patients with PC and 15 patients with BPH (pos. br.: 77%)/IBL: 46 patients with PC and 20 patients with BPH (pos. br.: 70%)] CONCLUSIONS: High total PSA levels of all assays are a very good indicator for the presence of prostate cancer. There is still concern to improve the differentiation between BPH and PC, when an intermediate or low value (< 95% specificity) is observed. The determination of Q is only useful in this range and it might be helpful for the clinicians decision to apply or avoid biopsy.

Clinical relevance of CYFRA 21-1, TPA-IRMA and TPA-LIA-mat in urinary bladder cancer.

The sera of 154 cancer patients were analyzed at primary diagnosis before any therapy to find out the clinical importance of CYFRA 21-1 (detecting cytokeratin 19-fragments) compared with the polyclonal TPA-IRMA and the monoclonal TPA-LIA-mat-assay (both measuring fragments of cytokeratin 8, 18 and 19). The reference group consisted of 100 healthy persons as well as 78 patients with exclusively benign urological diseases. We defined the cut-off values based on 95% specificity versus benign urological disorders. For CYFRA 21-1 the cut-off value was found to be 2.5 ng/ml, for TPA-IRMA 165 U/L, and for TPA-LIA-mat 136 U/L. Taking into account all stages CYFRA 21-1 showed a sensitivity of 31% versus 20% and 16% for TPA-IRMA and TPA-LIA-mat, respectively. Considering only the muscle invasive carcinomas 52% sensitivity for CYFRA 21-1 vs. 39% and 33% for TPA-IRMA and TPA-LIA-mat could be found. All three markers correlate with the stage of disease, CYFRA 21-1 to the highest degree (stage O: 16%, stage IV: 71%). CYFRA 21-1 shows the best sensitivity-specificity-profile and seems to be a recommendable marker for the follow-up of urinary bladder cancers except for the Ta-tumors which only rarely develop into muscle invasive cancers.

CYFRA 21-1 is not superior to SCC antigen and CEA in head and neck squamous cell cancer.

CYFRA 21-1 was compared to the most reliable tumor markers for squamous cell carcinoma of the head and neck (HNSCC), SCC antigen and CEA. Sera of 163 patients with primary and 40 patients with recurrent HNSCC were examined. 94 patients with non-malignant ENT-diseases served as the control group. To give a specificity of 95% the cut-off-values were as follows: SCC: 1.9 ng/ml, CEA: 3.8 ng/ml, CYFRA 21-1: 2.9 ng/ml. SCC had the highest sensitivity at the time of primary diagnosis (P) at 43% and 61% at relapse (R), compared to CEA with P: 35%, R: 40% and CYFRA 21-1 with P: 17%, R: 18%. We show that CYFRA 21-1 cannot offer additional information to the clinical outcome of patients with HNSCC, whereas combined analysis of SCC and CEA leads to a markedly increased sensitivity of 60% at primary diagnosis and of 79% in cases of tumor relapse.

Methodological and clinical evaluation of two automated enzymatic immunoassays as compared with a radioimmunoassay for neuron-specific enolase.

We evaluated the clinical and methodological features of the neuron-specific enolase radioimmunoassay (NSE RIA) (Pharmacia = Ph) with the neuron-specific enolase enzyme immunoassay (NSE EIA) on the ES 700 (Boehringer Mannheim = BM) and the NSE EIA on the Cobas Core System (Roche = Ro). A total of 253 serum samples obtained from 37 healthy persons, 45 patients with benign lung diseases, 124 patients with lung cancer (42 with small cell lung cancer, 23 with adenocarcinoma, 21 with squamous cell carcinoma, 11 with large cell carcinoma, and 27 with unknown histology), 34 with lung metastases, 7 patients with sarcoma and 6 patients with malign lymphatic diseases were stored at -80 degrees C and assayed retrospectively. The intra- and inter-assay imprecisions were lower for the automatized test systems than for the RIA. Correlation between the EIA's and the RIA was better for NSE (Ro) than for NSE (BM) (BM/Ph: r = 0.93 and slope = 0.54; Ro/Ph: r = 0.95, slope = 0.79), but weaker than the correlation between the two EIA's: over the whole range r = 0.96, neuron-specific enolase < 50 micrograms/l: r = 0.97, neuron-specific enolase < 20 micrograms/l: r = 0.92. Fixing the specificity at 95% versus benign lung diseases we found a cut off value of 11.9 micrograms/l for NSE RIA (Ph), 15.9 micrograms/l for NSE EIA (BM) and 13.5 micrograms/l for NSE EIA (Ro). Based on this specificity of 95% versus benign lung diseases as the clinically relevant reference group, the sensitivity for NSE RIA was 32% for all lung cancer and 45% for small cell lung cancer, for NSE EIA (BM) 35% for all lung cancer and 43% for small cell lung cancer, the NSE EIA (Ro) had a sensitivity of 42% for all lung cancer and 57% for small cell lung cancer. In a follow-up study of two patients with small cell lung cancer a good comparability for all three assays in the kinetics, but a marked difference in the neuron-specific enolase value levels was found. The results show that the NSE EIA (Ro) on Cobas Core system is the most sensitive assay for the detection of small cell lung cancer.