Neuron-specific enolase (NSE) in serum. Comparison of monoclonal versus polyclonal assay based on 392 blood samples.

Neuron-specific enolase (NSE) is the best described serum tumor marker for small cell lung cancer (SCLC). Almost all clinical studies carried out so far used assays involving polyclonal antibodies against NSE; the majority of the studies analyzed the samples by a RIA NSE kit. We evaluated a new monoclonal kit and compared it to the polyclonal kit. We analyzed 392 serum samples, 265 from patients with SCLC, 88 from non-small cell lung cancers (NSCLC) and 39 from children with neuroblastomas. We found a good correlation between the results of the two assays. When correlating NSE in SCLC as measured with the two assays with clinical data, we found the same sensitivity, prognostic impact and value in treatment monitoring. We conclude that the "new" monoclonal assay is a fully acceptable alternative to the "old" polyclonal assay.

The role of CA-242 and CEA in surveillance following curative resection for colorectal cancer.

This study was undertaken to evaluate the role of a new tumour marker, CA-242, alone or in combination with CEA in the practical management of colorectal cancer patients after potentially curative resection. A cohort of 149 patients who had undergone 'curative' surgery was followed up according to an intensive protocol in order to detect recurrent disease. Over a median tumour marker follow-up period of 24 months there were 25 recurrences in 24 patients. Both CEA and CA-242 alone detected half the local recurrences. The sensitivity of CEA was 84% for distant or mixed recurrence compared with 64% for CA-242. An abnormality of either CEA or CA-242 enabled detection of five out of six local recurrences and 17 out of 19 distant or mixed recurrences with a median lead time of 5 months for each marker. Both markers were elevated concurrently in only one local and 11 distant recurrences. While CA-242 alone is not superior to CEA, their combined use (either abnormal) has a high sensitivity (88%), specificity (78%) and negative predictive value (97%); this may be useful in reducing unnecessary investigations in follow-up programmes and as a guide to the initiation of further treatment for recurrent disease.

Commercial assays for serum osteocalcin give clinically discordant results.

Serum samples from 9 healthy controls and from subjects with primary hyperparathyroidism (n = 5), Paget disease (n = 3), pregnancy (n = 5), glucocorticoid therapy (n = 5), postmenopausal osteoporosis (n = 10), and renal failure (n = 10) were used to assess the clinical agreement among eight commercially available assay kits for osteocalcin (OC). These kits differ in their assay configurations (six radioimmunoassays, two immunoradiometric assays), standards (five bovine, three human), and antibodies (six polyclonal, two monoclonal). Individual results were divided by the mean OC of the control subjects for each assay and expressed as percentage deviations. The expected wide variation in absolute OC concentrations between kits was only partially reduced by this transformation. Agreement was equally poor when absolute OC concentrations were compared with the reference ranges quoted by the manufacturers. The discordance was particularly marked in renal failure, presumably because of immunoreactive fragments, and in osteoporosis. Systematic differences could not be attributed to assay format, species source of standard, or antibody specificity. We conclude that results cannot be compared between assays even when normalized against healthy subjects, and that standardization is needed.

Clinical evaluation of serum tissue polypeptide-specific antigen (TPS) in non-small cell lung cancer.

M3 is an epitope of the tissue polypeptide antigen detectable in the serum by immunoradiometric assay. This epitope is referred to as tissue polypeptide-specific antigen (TPS). We examined the pretreatment TPS level of 160 non-small cell lung cancer (NSCLC) patients and 71 patients who suffered from non-malignant pulmonary diseases. The upper limit of normal values was 140 U/l. Using this cutoff, the sensitivity and specificity were 36 and 90%, respectively. The TPS was significantly higher in NSCLC patients with an advanced stage, a mediastinal lymph node involvement or a poor performance status. This level was significantly higher in the group of patients for whom the disease proved to progress during chemotherapy. In univariate analysis, patients with a high TPS level proved to have a shorter survival than patients with a TPS < or = 140 U/l. In Cox's model analysis, performance status, stage of the disease and serum TPS were the only significant prognostic variables. The low sensitivity of TPS precludes its use for diagnosis. However, the pretreatment TPS level adds information to the management of NSCLC inasmuch as it predicts a low sensitivity to chemotherapy and a poor prognosis.

Clinical evaluation of serum tumour marker CA 242 in non-small cell lung cancer.

CA 242, a novel tumour carbohydrate antigen present in serum (upper limit of normal values: 20.0 U ml-1), has been measured in a group of 102 pathologically confirmed non-small cell lung cancer patients. The aim of the present prospective study was to identify any relationship between pre-treatment serum CA 242 level and different features of lung cancer including prognosis. Serum CA 242 was measured using the delayed europium lanthanide fluoroimmunometric assay. Sensitivity and specificity were 28.5% and 95.6% respectively. Its level was significantly lower in squamous cell carcinoma in comparison with non-squamous histologies (adenocarcinoma and large cell carcinoma). The CA 242 level was higher in metastatic disease (median: 15.3 U ml-1) in comparison with non-metastatic (median: 7.9 U ml-1; Mann Whitney U test; P < 0.003), and increased significantly from stage I to stage IV. In 50 patients who underwent chemotherapy, the serum CA 242 level was higher in non-responder patients when compared with responders (median: 16.8 U ml-1 and 9.5 U ml-1 respectively; Mann Whitney; P < 0.02). Univariate analysis of the entire population showed serum CA 242 levels were not related to survival. However, patients with unresectable non-small cell lung cancer and elevated CA 242 level proved to have a significantly shorter survival than those with a CA 242 < 20 U ml-1. In Cox's model analysis, stage of the disease and performance status were the only significant determinants of survival. We conclude that a high level of serum CA 242 (1) is significantly related to the stage of disease, (2) predictive of no response to chemotherapy but seems to add weak prognostic information to stage of disease and performance status, the main prognostic determinants of non-small cell lung cancer.

The use of tumour markers CEA, CA-195 and CA-242 in evaluating the response to chemotherapy in patients with advanced colorectal cancer.

Tumour markers CEA, CA-195 and CA-242 were measured in 33 patients undergoing chemotherapy for advanced colorectal cancer. The aim was to determine whether they could be used to accurately monitor the course of the disease, and reduce the need for imaging. Treatment with a 5-fluorouracil based regimen resulted in a partial response in nine patients (27%), whereas the remainder either had disease stabilisation or suffered from progression. Before treatment the CEA was elevated in 85% of patients and the CA-195 and CA-242 in 78%. All three markers were elevated in 70% and at least one elevated in 93%. CA-195 and CA-242 appeared to be co-expressed, by contrast with the CEA. When compared to the results of serial CT scanning the CEA correlated best with the course of the disease, the positive predictive value being 54% for a partial response, 77% for minor and partial responses combined and 100% for progressive disease. The corresponding values for CA-195 were 46%, 62% and 100% respectively and for CA-242, 50%, 67% and 100% respectively. Thus, although falling levels of markers overestimate the number of responses demonstrated by imaging, rising tumour markers invariably herald progressive disease. This was often evident up to 16 weeks before progression was observed on scanning. CEA is the most useful of the three markers in the monitoring of patients being treated for advanced colorectal cancer, but other markers may prove valuable if the CEA is normal. The use of tumour markers should reduce the need for regular scanning.