Diagnosis of Small Cell Lung Cancer by Pro Gastrin Releasing Peptide (ProGRP) Diagnostik des kleinzelligen Bronchialkarzinoms mittels Pro Gastrin Releasing Peptide (ProGRP) K. Yamaguchi 1 , Petra Stieber 2 Summary: ProGRP (Pro Gastrin Releasing Peptide), the mammalian counterpart to the amphibian bombesin, is the more stable precursor of the gut hormone gastrin releasing peptide (GRP) originally isolated from por- cine stomach. When compared to other oncological biomarkers of relevance for lung cancer like CEA, CYFRA 21-1 and NSE, the relatively new marker ProGRP has meanwhile proved not only to be more frequently released by small cell lung cancer (SCLC) cells but also more specific for both the tumor and the organ. The high discriminatory power of ProGRP is based on the facts that ProGRP release and subsequently ProGRP levels are very low in various benign disorders and that even malignant tumors other than SCLC (with the exception of medul- lary thyroid carcinoma) release minimal amounts of ProGRP,ifatall. Depending on the extent of the disease, 47 to 80% of small cell lung tumors release ProGRP. 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 com- plementary roles in the diagnosis of small cell lung can- cer. Keywords: tumor marker; ProGRP; lung cancer; small cell; SCLC. Zusammenfassung: Bei ProGRP handelt es sich um eine biologische Vorstufe des GRP (Gastrin Releasing Peptide), welches das Korrelat der Sa Èugetiere zum Bombesin der Amphibien darstellt und urspru Ènglichaus Schweinema Ègen isoliert wurde. Beim Vergleich mit anderen, fu Èr das Bronchialkarzi- nom relevanten, onkologischen Biomarkern wie CEA, CYFRA 21-1 und NSE stellte sich heraus, dass ProGRP nicht nur ha Èufiger von Zellen kleinzelliger Bronchial- karzinome freigesetzt wird, sondern auch im Hinblick auf die Tumor- und Organspezifita Èt den anderen Mar- kern u Èberlegen ist. Das hohe Diskriminationsvermo Ègen von ProGRP liegt darin begru Èndet, dass ProGRP im Rahmen der verschiedensten benignen Erkrankungen sowie auch von anderen malignen Tumoren (mit der Ausnahme des medulla Èren Schilddru Èsenkarzinoms) ho Èchstens in sehr geringen Mengen freigesetzt wird. Je nach Ausdehnung der Tumorerkrankung setzen 47 bis 80% der kleinzelligen Bronchialkarzinome ProGRP frei. Somit geht aus den meisten Publikationen hervor, dass ProGRP der Neuronspezifischen Enolase NSE u Èberlegen ist, aber wie schon der unterschiedliche pa- thophysiologische Hintergrund vermuten la Èsst, haben diese beiden Teste eine klare additive Empfindlichkeit und erga Ènzen sich in der Diagnostik des kleinzelligen Bronchialkarzinoms. Schlu Èsselwo Èrter: Tumormarker; ProGRP; Bron- chialkarzinom; kleinzellig; SCLC. O n a worldwide basis, lung cancer is the most frequent and most deadly malignancy with contin- uously growing incidence. Despite many efforts to improve diagnosis and therapy, the 5-year survival rate of lung cancer patients increased only slightly over the last decades and is now around 13%. The prognosis and therapeutical concept in lung cancer depends mainly on the extension of the tumor and its histolog- ical type. Lung cancer is classified as small cell lung cancer (SCLC), squamous cell carcinoma, primary adenocarcinoma and large-cell carcinoma. Small cell lung cancer accounts for 20 to 25% of the new cases of bronchogenic carcinoma and differs clinically and bio- logically due to its neuroendocrine differentiation from the other histological types, which behave similarly concerning prognosis and therapy and are thus pooled into one group as non-small-cell lung cancer (NSCLC). Since the incidence of distant metastases at the time of primary diagnosis is high in SCLC and these tumors are, in contrast to non small cell lung carcinomas (NSCLC), very sensitive to chemotherapeutic reagents and radiotherapy, primary systemic therapy plays an important role in the management of these patients. Neuroendocrine markers like Neuronspecific Eno- lase (NSE), Chromogranin A (CGA), Synaptophysin, 26 J Lab Med 2003; 27 (1/2): 26±30 1 National Cancer Center Research Institute, Tokyo, Japan. 2 Inst. of Clinical Chemistry, University of Munich, Germany. Correspondence: Dr. med. Petra Stieber, Institut f. Klinische Che- mie, Klinikum der Universita Èt Mu Ènchen ± Groûhadern, Marchioni- nistr. 15, 81366 Mu Ènchen, Germany. Fax: +49 89 70 95 62 98 E-mail: Stieber@klch.med.uni-muenchen.de ã 2003 Blackwell Verlag, Berlin Onkologie Redaktion: Petra Stieber