The International Journal of Biological Markers

External immunoscintigraphy (IS) is a new imaging tool to diagnose, stage and follow-up solid malignancies. Monoclonal antibodies are raised to tumor-associated antigens, radiolabeled and when injected in the patient localize to the tumor. Detection is with nuclear medicine gamma camera.

In colorectal cancer, immunoscintigraphy can be beneficial to the surgeon. With primary colorectal carcinoma, IS detects synchronous primaries, identifies lymph node metastasis, determines extent of disease and detects occult metastasis. Postoperatively, in high-risk patients (Dukes B₂, B₃ and C lesions) IS assists in the follow-up for recurrence. Particular advantage with IS is seen in pelvic, mesenteric and retroperitoneal recurrences. Rising serum CEA and negative conventional cross-sectional imaging can often be clarified as to site of disease with IS.

IS contributes significantly to surgical decision making with alterations in management based on radiolabeled monoclonal antibody scans in 25 - 32% of primary and recurrent colorectal cancer cases.

Peripheral blood samples from 55 previously untreated leukemia patients (33 males, 22 females) were analysed for terminal deoxynucleotidyl transferase (TdT) activity. TdT was significantly higher in patients with acute myelogenous leukemia (AML; P < 0.001), chronic myelogenous leukemia (CML; P < 0.05) and acute lymphoblastic leukemia (ALL; P < 0.001) when compared with controls. One patient with chronic lymphocytic leukemia (CLL) had undetectable TdT. Among leukemic patients, ALL patients had higher concentration of TdT than CML and AML patients. Females had higher TdT activity than males, although the difference between the two groups was not statistically significant. 68% TdT⁺ and 32% TdT^– patients were in blastic crisis. Patients with more than 10% of blasts in the circulation had significantly higher TdT than blast-negative patients (P < 0.001). No difference in survival was observed between TdT⁺ and TdT^– groups. From these results, we conclude that the absolute TdT concentration is of little prognostic value in leukemia patients.

Eighty-eight patients with head and neck cancer were prospectively monitored, before and after treatment, by means of simultaneous serum SCC, CEA and TATI measurements. Thirty-two (36.6%) patients had early stages (I, II, III) and 56 (63.4%) advanced (stage IV) or recurrent disease. Pre-treatment serum SCC levels were elevated in 20.4% of patients, CEA in 27.2% and TATI in 4.5%. There was no correlation between the incidence of TATI elevation and tumour burden; this marker did not increase with progressing disease stages. CEA and SCC had low sensitivity in the early stages of head and neck cancer and reached 35.7% (20/56 patients) and 25% (14/56 patients) in stage IV or recurrent disease. Despite the low sensitivity of these tumour markers, there was a correlation between tumour marker levels and the course of the disease. This study indicates that the routine assessment of SCC, CEA and TATI serum levels is of no value. However, it can be used as a potential tool for monitoring the efficacy of individual therapy in both early and advanced stages of head and neck cancer.

In 111 patients with ACC we studied CEA, FP, CA-125 and CA 19.9 during therapy and follow-up. Marker determination was performed every two months. CEA was elevated (> 5 ng/ml) in 82%, αFP(> 15 ng/ml) in 0%, CA-125 (>38 U/ml) in 37%, CA 19.9 (> 30 U/ml) in 64% of the patients. We did not find significant differences between the sensititivity of CEA alone and that of the combination of CEA + CA-125 (86%), CEA + CA 19.9 (87%), CA-125 + CA-19.9 (71%) and CEA + CA-125 + CA 19.9 (88%). We did not find any correlation between the level of positivity of the markers and the clinical parameters we examined. When serial determinations were carried out, CEA showed the best indication of response to treatment, followed by CA 19.9. In the evaluation of the response to chemotherapy we found that CA 125 presented significant percentages of false-positive (9%) (P < 0.008) and false-negative (8.1%) (P < 0.008) results, compared to CEA and CA 19.9. CA 125 did not demonstrate any utility for the follow-up of patients with colorectal cancer although increased values were found in 37%. We conclude that CEA is currently the best marker for the follow-up of patients with colorectal cancer. The combination of CEA and CA 19.9 had some utility in follow-up, without significantly improving CEA results

Serum and pleural effusion fluid were tested for CEA concentration in 83 advanced breast cancer patients, in 43 of whom CA 15-3 was also determined.

All pleural effusions were clinically malignant. The sensitivity of the CEA test for the presence of pleural metastases was closer to that of the CA 15-3 test in effusion (0.59 and 0.79, respectively) than the sensitivity of CEA compared to CA 15-3 in serum (0.43 vs. 0.79). The use of two markers combined with cytology increased the diagnostic rate from 48% (cytologically positive) to 88% (cytologically positive and/or with one or both markers increased in effusion). A high diagnostic rate in cytologically negative effusions (65%), and in effusions presented as the sole metastatic involvement (100%), points to the clinical value of these two markers. Our results show that markers produced by pleural metastases may be secreted either into the effusion fluid or into serum, or both. This finding, as well as some other observations, are discussed in the present paper.

the purpose of this study was to determine the role of Tissue Polypeptide Antigen (TPA) immunostaining in the evaluation of aspiration smears from solid breast nodules and to discuss its possible clinical applications. Seventy-one cytologic specimens were studied; 52 were carcinomas, 15 fibroadenomas and 4 fibrocystic dysplasia. TPA was visualized with the peroxidaseantiperoxidase method, using 3-3 ‘diaminobenzidine as chromogen and hematoxylin as counterstaining. The incidence of TPA-positive aspiration smears was 88.5% in the carcinomas and 26.7% in the fibroadenomas. The four cases of fibrocystic dysplasia showed variable behaviour. The intensity of the TPA staining varied from – to + + + and was most frequently high in the carcinomas. The results of this research show a good correlation between a diagnosis of carcinoma and TPA positivity in fine needle aspirates of solid breast nodules.

The mucin-like carcinoma-associated antigen (MCA) is a mucin with a molecular weight of 350 - 500 kD. It circulates in the serum and its serum content can be determined with the Cobas Core MCA EIA test. Patients with breast cancer show elevated MCA serum levels. The molecule has a polypeptide backbone consisting of three parts: the C-terminus the N-terminus and the transmembrane sequences. The protein is heavily glucosylated with carbohydrate side chains that contain fucose, galactose and N-acetyl galactosamine. The antibody b-12 recognizes a repetitive epitope on the peptide portion of the MCA molecule. The epithelial mucin, which is coded by a unique gene, was cloned using PCR technology. Peptides corresponding to the N- and C-terminus were expressed in E. coli. Analysis of the purified peptides revealed molecular weights of 12 and 18 kD.

Mucin-like Carcinoma-associated Antigen (MCA) has been associated with many breast cancers. The aim of this study was to evaluate MCA in tumor tissue and serum as a potential tumor marker for prognosis and disease monitoring. MCA levels were determined in the tissue of 196 patients with primary breast cancer, 25 with metastatic disease and 25 patients with benign diseases, in pellet and/or cytosol. MCA levels were also determined in the serum of 50 patients with benign diseases, 148 with primary breast cancer (Mo), 150 with metastatic breast cancer (MT), and 200 with no clinical evidence of disease (NED). MCA tissue concentrations in pellet and cytosol were similar: 66.7 + 251 U/mg and 41.1 + 53 U/mg, respectively. No relationship between MCA levels and tumor size or nodal involvement was found. Higher MCA levels were observed in patients with ER + or PgR + tumors than in those with ER- or PgR- tumors (p < 0.01). Patients with MCA pellet concentrations lower than 10 U/mg of protein had shorter disease - free intervals (DFI) than those with higher values (p < 0.05).

Abnormally high serum levels of MCA were found in 8% of patients with benign diseases, 4% of NED patients, 22% of Mo patients, and in 76% of MT cases. In primary breast cancer MCA values were related to tumor size and nodal involvement. A trend toward a lower DFI in patients with elevated presurgical MCA levels was observed but was of no statistical significance. These differences became statistically significant when patients were subdivided according to nodal status, with shorter DFI in those without nodal invasion (p < 0.05). In metastatic patients, changes in serum MCA were related to the tumor's response to treatment in 82% of cases. The highest MCA values were found in patients with liver or bone metastasis and the lowest values were found in those with locoregional recurrence. In conclusion, although MCA is not a specific tumor marker, it can be useful as a prognostic factor (tissue and serum) and in monitoring metastatic patients.

Mucin-like Carcinoma-associated Antigen (MCA) is a glycoprotein belonging to the mucin family; it is defined by the monoclonal antibody b-12. Mucins represent an interesting group of tumor markers and are widely utilized in the clinical monitoring of neoplastic patients. These molecules show a certain degree of tissue specificity and MCA is preferentially associated with breast tissue.

Several studies have demonstrated that patients with breast cancer usually have high MCA serum levels. In this paper the experience of the National Cancer Institute of Milan with the clinical use of MCA in breast cancer patients is reported. The observed sensitivity of the MCA test was poor in patients with early-stage disease, while it was acceptable in patients with advanced breast cancer. MCA concentrations appeared to be directly related to disease spread. A clear relationship was seen between MCA levels and lymph-nodal status. The highest MCA plasma levels were observed in patients with metastatic disease. In this group of patients the sensitivity of the test on the basis of a cut-off of 11 U/mL was 52%.

MCA is a mucin-like carcinoma-associated antigen which has been found in all breast cancer independent of histological type and degree of differentiation. A two-step solid-phase EIA was developed and the serum concentration of MCA was measured in 176 breast cancer patiens after surgery. Using a cutoff of 11.0 U/ml the test showed a sensitivity of 77% and a specifity of 82% when compared to clinical status. The predictive value of this tumor marker was 72% for a positive diagnosis and 93% for a negative diagnosis. Based on these observations it is recommended that determination of MCA values take place 2 to 3 times in the first postoperative week in all women with surgically treated mammary carcinoma. These MCA values should then serve as reference for further determinations, which should be performed at each check-up. A subsequent increase in the MCA value should be considered as a first sign of metastasis.

The breast cancer marker Mucin-like Carcinoma-associated Antigen (MCA) was evaluated in a version that has been adapted to a new enzyme immunoanalyser, the Cobas^R Core. The two-step sandwich assay has a short total assay time of less than 60 minutes. Standard curves are stable for at least 2 weeks. The coefficients of variation for the inter-assay precision ranged between 3.6% and 7.8%, but were mainly below 5%. Single determinations of patient values from different runs correlated also very closely (R = 0.99). The dilution linearity for a set of 14 sera exhibited recovery rates mostly ranging from 90% to 110%. From 165 blood donors investigated, more than 99% had values below the cut-off of 11 U/ml. As demonstrated for pathological sera, the automated and manual versions showed a high degree of accordance (R = 0.98). The investigation presents convincing evidence that the Cobas Core MCA EI A running on a Cobas^R Core analyser guarantees a high analytical reliability and reproducibility.