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.

Analysis of Variance↗

PubMedDate not supplied

Significance of the tumour markers CA 125 II, CA 72-4, CASA and CYFRA 21-1 in ovarian carcinoma.

We compared the tumour marker CA 72-4 and the new markers CASA and CYFRA 21-1 with the established marker CA 125II in follow-up care and control of efficacy of treatment in ovarian cancer in order to determine whether there are differences in recognizing ovarian carcinomas of different histological type. The investigation was done retrospectively on serum samples frozen at -80 degrees C obtained from 262 subjects, among them 50 healthy women, 53 sera with benign gynecological diseases and 159 sera with ovarian cancer, 72 of them at the time of primary diagnosis. We used commercially available kits: CA 125 II: Centocor RIA, CASA: Medac EIA, CA 72-4: Centocor RIA and CYFRA 21-1: Boehringer EnzymunR ELISA. Fixing specificity at 95% versus benign gynecological diseases as a clinically relevant reference group, we found cut-off values of 160 U/mL for CA 125II, 6.5 U/mL for CASA, 6.8 U/mL for CA 72-4 and 2.4 ng/ml for CYFRA 21-1. Based on this specificity we can compare the corresponding sensitivities at the time of primary diagnosis (n = 72): CA 125 II 47%, CA 72-4 47%; CASA 31% and CYFRA 21-1 44%. Regarding histological types of ovarian carcinomas, we found a sensitivity of 50% for CA 125 II and CASA, 36% for CA 72-4 and 33% for CYFRA 21-1 in serous ovarian cancer (n = 53), 21% for CA 125 II and CASA, 36% for CYFRA 21-1 and 43% for CA 72-4 for mucinous ovarian cancer (n = 27). Serous ovarian carcinomas were classified by higher FIGO-stages than mucinous ovarian carcinomas. Additional sensitivities were found at the time of primary diagnosis for the combination of CA 125 II and CA 72-4 and in serous ovarian cancer for CA 125 II and CASA. According to our results, at the time of primary diagnosis the combined determination of CA 125 II and CA 72-4 is useful. If both are negative, determination of CASA can be helpful. For follow-up care and control of efficacy of treatment the preoperative positive or leading marker is sufficient.

Adenocarcinoma, Mucinous↗

PubMedDate not supplied

Serum marker combinations in human breast cancer (review).

Breast cancer markers (TM) are mainly useful for monitoring the course of disease after diagnosis and first line treatment with the control options of primary treatments early recognition of reactivation and efficiency control of palliative treatment. The best single and established marker is a polymorphic epithelial mucin of the MUC-1 family the prototype of which is CA 15-3 (successive markers: MCA, CA-549, TAG-12, CAM 26/29) followed by CEA with lower diagnostic sensitivity and specificity and TPA/TPS reflecting more the proliferative activity. Besides former TM combinations of CEA with one or more less specific markers (e.g. PAM, CRP, beta 2m, ferritin, GCDFP, HCG, total or boney AP, gamma GT), more recent studies recommend the use of fewer markers such as TPA/TPS + CEA or CA 15-3, CA 15-3 + CEA or MCA, CA M26 + CA M29, TAG12 + CA 15-3 + MCA and CEA + CA 15-3 + ESR.

Antigens, Tumor-Associated, Carbohydrate↗

PubMedDate not supplied

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.

Antigens, Neoplasm↗

PubMedDate not supplied

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.

Antigens, Neoplasm↗

PubMedDate not supplied

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.

Antigens, Tumor-Associated, Carbohydrate↗

PubMedDate not supplied

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.

CA-19-9 Antigen↗

PubMedDate not supplied

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.

CA-125 Antigen↗