Tumor M2-pyruvate kinase in the follow-up of inoperable lung cancer patients: a pilot study
Introduction
New regimes for chemotherapy of inoperable lung cancer patients increase the probability of survival. This increase in therapeutic efficiency justifies the use of tumor markers for monitoring the progression of the disease. In inoperable lung cancer patients and especially in small cell lung cancers chemotherapy plays an important role in tumor management. Because carcinomas often recur and become resistant to treatment, early diagnosis, more accurate evaluation of treatment and early detection of progression are needed to improve survival of patients. Reliable tumor markers are useful for determination of the effectiveness of therapy.
In this prospective study we evaluated a new tumor metabolic marker, the Tumor M2-PK, to monitor response to therapy. A reduction in marker concentration indicates effective therapy, an increase in concentration is evident of tumor progression.
Tumor M2-PK is an isoform of pyruvate kinase and is expressed during multi-step carcinogenesis [1]. The metabolic state of tumor cells differs from that of normal proliferating cells [2]. Tumor formation is usually linked to an increased aerobic glycolysis. Some glycolytic enzymes, such as pyruvate kinase can divert glycolytic metabolites, which are normally used for energy production, to synthetic processes. Several isoforms of pyruvate kinase are expressed in a tissue-specific manner (type L-PK, R-PK, M1-PK and M2-PK) [3]. The first step during multi-step carcinogenesis is the loss of the tissue-specific isoenzymes, e.g. L-PK in liver and kidney and M1-PK in brain and muscle, followed by the subsequent expression of the M2-PK isoenzyme. This was demonstrated for renal cell carcinoma [4], [5], [6], gastrointestinal cancer [7], colon [8], breast [9], and lung cancer [10], [11], [12].
The goal of this study was to determine the efficiency by which the disease state of lung cancer patients could be monitored using this new tumor metabolic marker. In the present, prospective study Tumor M2-PK levels were determined both before and after therapy as well as at time of relapse.
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Subjects
In this correlational study n=57 consecutive patients with histologically confirmed lung cancer were prospectively examined. Histological classification of the primary lung tumor cases [13] and tumor staging prior to therapy are presented in Table 1. The cTNM stages according to UICC recommendations were used in non-small-cell lung cancer (NSCLC) patients. One patient in stage Ib was inoperable because of prior pneumectomy with severe combined restrictive and obstructive lung function damage.
Tumor M2-pyruvate kinase in patients with lung cancer before and after treatment
Pretreatment concentrations of Tumor M2-PK ranged from 4.4 to 157.5 U/ml, median 18.8 U/ml, mean 27.2 U/ml and were elevated (according to the manufacturer s cut-off) in 38 (67%) of 57 patients. Concentrations of Tumor M2-PK ranged from 4.4 to 85.1 U/ml, median 11.9 U/ml, mean 18.6 U/ml and were initially elevated in 8/21 (38%) of the small-cell lung cancer patients. In squamous carcinomas Tumor M2-PK ranged from 6.9 to 65.8 U/ml, median 22.2 U/ml, mean 28.3 U/ml and were elevated in 11/12 (92%)
Discussion
In lung cancer patients the diagnostic accuracy of the clinical assessment by the WHO criteria are predominantly based on examinations by X-ray or computerized tomography. However, small-cluster distribution of tumor cells in the environment of the primary tumor or especially occurrence of metastases in various lymph nodes, in the brain, in the bone marrow or other organs cannot easily be detected. Tumor markers may represent the total body tumor load. Rising tumor marker concentrations in lung
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