ARCHITECT ProGRP Progastrin-Releasing

A relevant marker for small cell lung

The survival rate of patients suffering from lung cancer is very low and is dependent on tumor type. While only approximately 20 % of patients with non-small cell lung cancer (NSCLC) have a life expectancy of more than five years, this number is halved for those diagnosed with small cell lung cancer (SCLC). SCLC progresses very quickly, forms metastases early and is difficult to detect using imaging techniques. There are chemotherapy and radiotherapy options available but, in contrast to NSCLC, surgery is not possible. As a consequence, early detection and histological determination of lung cancer is of utmost importance to enable the correct choice of therapy. Numerous publications have shown that the biomarker ProGRP (progastrin- releasing peptide) can play a significant role in achieving these goals.

3D image of a lung cancer (arrow) made up from CT layers Source: en.wikipedia.org Progastrin-Releasing Peptide

ProGRP (pro -releasing peptide) is a precursor of gastrin-releasing peptide (GRP). GRP is a gut , originally isolated from porcine , with the ability to release gastrin. Additionally, GRP is present in the neuroendocrine cells in fetal lung and in SCLC. ProGRP is a highly specific tumor marker for SCLC. ProGRP is released in measurable amounts early in SCLC and is independent of the tumor size. In various benign conditions and other malignant tumors, ProGRP is released in very small quantities only. This explains the high discriminative power of ProGRP. Because ProGRP release is largely independent of tumor stage, it can be used to identify lung cancer at a very early stage.

Clinical Applications

• ProGRP has been demonstrated as a valuable marker for differential diagnosis between NSCLC (Non-Small Cell Lung Cancer) and SCLC (Small Cell Lung Cancer) • ProGRP can be used as a predictor for progression monitoring and therapy control of small cell lung cancer • If used in conjunction with other tumor markers, ProGRP has a potential to aid in the histological classification of Lung Cancer ARCHITECT ProGRP

The ARCHITECT ProGRP assay is a two-step immunoassay for the quantitative determination of ProGRP in human serum and plasma on the ARCHITECT Immunoassay Analyzer.

Assay Characteristics Method Two-step Chemiluminescent Microparticle Immunoassay (CMIA) Dilution Automated, 1:10 Time to first result 28 minutes Throughput i 2000s r Up to 200 tests per hour Functional sensitivity ≤ 3 pg/mL Calibration range 0 – 5.000 pg/mL Calibrators 6 points: Liquid ready to use Controls 3 levels Sample Type Human serum and plasma; preferable is the use of plasma, due to a longer stability of the analyte after blood draw Reagent onboard stability 30 days

Conclusions from Publications

“In summary, ProGRP is the tumor marker of choice for SCLC, and NSE is a complementary tumor marker in this histological type.” R. Molina et al., Anticancer Research; 2007, 25 (3A): 1773 – 1778

“Detection of ProGRP in the serum of samples of a patient suffering from SCLC with a clinical relevant concentration shows the potential of the method in diagnosis, prognosis, and monitoring of the disease.” B. Winther et al., J Sep Schi 2007, 30 (16): 2638 – 2646

“Thus, in most publications, the diagnostic sensitivity of ProGRP has been reported to be higher than that of NSE. However, as can be expected from the different pathophysiologic background of ProGRP and NSE, these two analytes have a clear additive sensitivity in SCLC and play complementary roles in the diagnosis of small cell lung cancer.” P. Stieber; ProGRP – a Diagnostic Biomarker for Small Cell Lung Cancer; White Paper 2008

“Changes of ProGRP level seem to be more precise than those of NSE as a tool for monitoring therapy and, together with NSE, determinations of ProGRP allow more reliable prediction of relapses and assessment of prognosis in SCLC limited disease patients.” E. Wojcik et al., Anticancer Research; 2008, 28: 3027 – 3034

“ProGRP provides important insight into the neuroendocrine differentiation of lung cancer, particularly in SCLC, SCLC-NSCLC, undifferentiated lung carcinoma and carcinoids.” G. Bubanovic et al., Col. Antropol 2008, 32 (4): 1155 – 1164

“The ProGRP sensitivity in SCLC, the absence of false positive results in samples with hemolysis, the greater differences between normal ranges and the levels found in SCLC patients, and the higher specificity in other malignancies support ProGRP as the tumor marker of choice for SCLC.” “Tumor marker determination in patients with suspicious signs of lung cancer reveals the histological diagnosis in the majority of lung cancer patients in a few hours.” R. Molina, European Journal of Clinical & Medical Oncology; December 2009, 1:(2)

Abbott GmbH & Co. KG Abbott Diagnostics Max-Planck-Ring 2 65205 Wiesbaden, Germany Tel. (+49) 61 22 58 0 Fax (+49) 61 22 58 12 44 ARCHITECT is a trademark of Abbott Laboratories in various jurisdictions. www.abbottdiagnostics.com All other trademarks are the property of their respective owners. AN2102/uk Novel Markers “ARCHITECT ProGRP” 02/10/x