Utility of serum tumor markers as an aid in the differential diagnosis of patients with clinical suspicion of cancer and in patients with cancer of unknown primary site

Abstract

Cancer may be diagnosed in advanced stages, when the patient has already developed metastasis, with symptoms that can be also observed in benign diseases. The objective of this study was to evaluate tumor marker sensitivity and specificity in the differential diagnosis of patients with suspected signs of cancer. We studied 2.711 consecutive patients admitted to the Internal Medicine Department of our hospital with suspected cancer; 1.240 patients had non-malignant processes and 1.471 had malignant disease. Determinations were considered positive for suspected malignancy when serum levels were carcinoembryonic antigen >15 ng/ml (>20 in patients with renal failure or liver disease), alpha fetoprotein >40 ng/ml (>80 ng/ml in patients with liver diseases), carbohydrate antigen (CA) 19.9 > 200 U/ml (>500 U/ml in patients with liver diseases or gamma glutamyl transpeptidase (GGT) <150 UI/L or effusions; >1.000 U/ml in patients with jaundice or GGT > 150 UI/L), neuron-specific enolase >45 ng/ml (renal failure >50 ng/ml; samples with hemolysis were excluded), prostate-specific antigen > 30 ng/ml (excluding acute prostatitis), tumor-associated glycoprotein-72 >80 U/ml, cytokeratin 19 fragment 21-1 > 7.5 ng/ml (>19 ng/ml in patients with renal failure; >11 ng/ml in patients with liver cirrhosis or jaundice), >3.5 ng/ml for squamous cell carcinoma (excluding patients with renal failure or skin disorders), CA 15.3 >100 U/ml, and CA 125 >350 U/ml (>600 U/ml in patients with pleural effusion and >900 U/ml in those with ascites). There was a specificity of 97.6% in patients without malignancy, 67.4% of sensitivity in patients with malignancy, and 75.4% of sensitivity in the 1,280 patients with epithelial tumors (53.7% in patients with locally advanced tumors and 79.4% in patients with metastases). Sensitivity was 81.4% in patients with cancer of unknown primary site. Tumor markers were useful in the differential diagnosis between epithelial and non-epithelial tumors, brain masses (metastases vs. primary tumors), and between benign or malignant origin of different clinical situations such as wasting syndrome, effusions, liver or bone lesions, and effusions with a positive predictive value higher than 95%. Tumor markers are useful as an aid in the evaluation of the risk of cancer of these patients with suspected cancer and may be useful to reduce the hospitalization time, morbidity, and the number of diagnostic tests required for diagnosis.

Multicenter evaluation of a new progastrin-releasing peptide (ProGRP) immunoassay across Europe and China

“…ProGRP showed clear differential diagnosis between SCLC and NSCLC in serum, with 78% sensitivity at 95% specificity in the NSCLC cohort, as previously noted with the ARCHITECT ProGRP assay [16,17,21,36]. No clinically relevant differences between sites were noted in the NSCLC and SCLC cohorts.…”

“…As NSE is present in platelets and erythrocytes, samples with hemolysis must be excluded and rapid storage of samples is essential [14]. ProGRP accurately discriminates between NSCLC and SCLC [16,17] and is rarely elevated in other malignant diseases or in benign conditions, except in patients with renal insufficiency, neuroendocrine tumors (NET) of the lung and medullary carcinoma of the thyroid (MCT) [16][17][18][19][20][21][22].…”

Pleural Fluid Tumour Markers in Malignant Pleural Effusion with Inconclusive Cytologic Results

“…Previous studies have demonstrated the clinical utility of tumour markers in the differential diagnosis of pleural diseases [5][6][7][8][9][10][11]13 , but depending on tumour markers in pleural fluid for diagnosing mpe is controversial. However, most authors felt that quantification of a panel of tumour markers could improve the cytologic diagnosis and should be considered in selected cases of inconclusive diagnosis of pleural effusions.…”

“…n As a supplementary method for diagnosing mpe n For the early detection of pleural metastasis n As tool to assist in identifying a primary tumour site Controversy with respect to the general usefulness of the technique remains [5][6][7][8][9][10][11] . Quantification of tumour markers in pleural fluid could be indicated in cases of undetermined causes in the presence of a strong clinical suspicion of malignancy or when cytology results were inconclusive in patients with a prior history of cancer.…”

Tumor marker analyses in patients with brain metastases: patterns of practice and implications for survival prediction research

“…It is also important to realize that abnormal markers might result from concomitant liver or kidney disease rather than the cancer itself. Tumor marker analyses were more common in patients with brain metastases detected at initial cancer diagnosis, i.e., when they might aid in the differential diagnosis between primary and secondary brain tumors or different types of malignancy [19]. They were often performed in an unselected manner before histology was available.…”