ProGRP – tumour markers for diagnosis, progress monitoring and therapy control in small-cell lung cancer

Prognosis and therapy options for lung cancer are based, on the one hand, on the extent of the tumour at the time of initial diagnosis and, on the other hand, on its histological classification. Lung cancers can be assigned to two histological subtypes: non-small-cell lung cancer (= NSCLC) and small-cell lung cancer (= SCLC).

SCLCs account for about 25 % of all lung cancers. They grow more rapidly, metastasise early on and are often inadequately represented by means of imaging procedures. Thus, they are usually only diagnosed at an advanced stage. Treatment options are chemotherapy and radiation therapy. This explains the need for an early diagnosis and precise histological assignment.

Numerous studies have shown that the neuropeptide ProGRP (pro gastrin-releasing peptide) is a tumour marker that is not only suitable for progress monitoring and therapy control of small-cell lung cancer, but – due to its very high discrimination ability – it is also suitable as a marker for diagnosing SCLC.

The high discrimination capacity of ProGRP arises from the fact that this marker is released in only very small quantities in benign lung diseases as well as with other malignant tumours, including NSCLC (exception: medullary thyroid cancer). In contrast, very high concentrations are usually found in patients with SCLC, even when only limited expansion of the tumour is found.

A ProGRP release of > 200 pg/ml is a strong indication of the existence of primary lung cancer and indicates with a probability of > 99 % the presence of small-cell lung cancer. A ProGRP release > 100 pg/ml – regardless of its histopathological classification – is a clear indication of a mixed histology with a small-cell component.
(Yamaguchi K., Stieber P. Diagnosis of small lung cancer by Pro Gastrin Releasing Peptide [ProGRP]. J. Lab. Med 2003; 27: 26-30).

ProGRP has therefore proven to be clearly superior in comparison to other markers relevant for lung cancer oncology, such as CEA, CYFRA 21-1 (NSCLC) and NSE (SCLC) in regard to the diagnosis and differential diagnosis of ambiguous lung tumours and, in particular, for the differentiation between small-cell and non-small-cell lung cancer.

Compared with NSE, the marker which was previously used for monitoring and therapy control of SCLC, ProGRP achieves a significantly higher diagnostic sensitivity (64 % vs. 43 %), and the increased sensitivity is even more pronounced in patients with early tumour stages (limited disease).

ProGRP cannot, however replace the use of NSE in SCLC, since either only ProGRP or only NSE is expressed in approx. 15 % to 20 % of the patients. It is therefore recommended that a combination of both parameters be used, at least for the primary diagnosis. As has been demonstrated in numerous studies, diagnostic sensitivity for SCLC can still be further improved by the combined use of both parameters.

Indications

  • Suspected lung cancer
  • Clarification of ambiguous pulmonary nodules
  • Suspected tumour-induced polyneuropathy
  • Therapy monitoring and after-care of small-cell lung cancer and other small-cell cancer and of medullary thyroid cancer.

Method
Fully automated chemiluminescence micro-particle immunoassay

Materials
serum, plasma (EDTA, Na heparin, Li heparin)

Pre-analytical interference factors
Haemolysis (> 500 mg/dl), microbial contamination, fibrin, storage time at room temperature > 3 hours.
To avoid longer times, store serum or plasma at 2-8 °C.

Reference ranges
Normal people (median) < 36.7 pg/ml
95 % of patients with benign pulmonary disease < 38 pg/ml

Please note: Determining ProGRP is currently not part of the service catalogue of statutory health insurance.

To top

Back