CEA, CYFRA 21-1, NSE, and ProGRP in the diagnosis of lung cancer: a multivariate approach

We retrospectively studied the single and combined diagnostic value
of carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA
21-1), neuron specific enolase (NSE) and pro-gastrin-releasing
peptide (ProGRP), which were routinely analysed in patients with
lung tumours of unknown origin at the time of admission to
hospital. Inclusion criteria were the determination of CEA
(AxSYM/Abbott), CYFRA 21-1 (ElecSys/Roche) and NSE
(Kryptor/Brahms). We examined 1747 patients, where 1325 suffered
from lung cancer (LC; small cell lung cancer, SCLC: n=194;
non-small cell lung cancer, NSCLC: n = 1015; others: n = 116), 318
from benign lung diseases and 104 from lung metastases due to
another primary malignancy. As ProGRP (ELISA ALSI/IBL) became
available only recently, there are less data points of this marker.
In total, 99.8% of LC patients released at least one of the four
biomarkers (defined as values exceeding the median of healthy
controls), and for the discrimination between benign disease (BID)
and malignant lung disease each marker reached 100% tumour
specificity at high levels (CEA: 20 ng/mL; CYFRA 21-1: 40 ng/mL;
NSE: 45 ng/mL; ProGRP: 250 pg/mL). At a specificity of > 99%,
ProGRP reached the highest diagnostic efficacy for SCLC with 57%
true positive results, CEA had the highest capacity (17%) to detect
malignant lung tumours in general and adenocarcinomas of the lung
with 29%. CYFRA 21-1 was dominant for squamous cell carcinomas
(12%). Combining the four markers leads with the prerequisite of
high specificity (> 99%) to 50% true positives for malignant
lung tumours, 44% for NSCLC, 36% for squamous cell carcinomas, 53%
for adenocarcinomas, and 78% for SCLC, respectively. In cases of
lung tumours of unknown origin, the combined use of CEA, CYFRA
21-1, NSE and ProGRP is useful for the differentiation between
benign and primary or secondary malignant disease and suggests the
assignment to histological subtypes.