Cancer Letters

Cancer Letters

Volume 193, Issue 1, 10 April 2003, Pages 91-98
Cancer Letters

Tumor M2-pyruvate kinase in the follow-up of inoperable lung cancer patients: a pilot study

https://doi.org/10.1016/S0304-3835(02)00720-6Get rights and content

Abstract

Tumor markers were used for disease monitoring in lung cancer patients. The goal of this pilot study was to determine the diagnostic efficiency of a new tumor metabolic marker, Tumor M2-pyruvate kinase (Tumor M2-PK) for the detection of tumor growth in inoperable lung cancer patients.

Fifty-seven consecutive and primary inoperable lung cancer patients were included in this prospective study. Changes in plasma levels of Tumor M2-PK were compared to the clinical course of the disease. Clinical monitoring was evaluated according to the standard criteria of the WHO. Of the 57 patients, 19 were in remission, 18 showed signs of stable disease and there were 20 tumor progressions under therapy. In the further follow-up after treatment, tumor relapse occurred in 30 patients. Tumor M2-PK was measured in plasma before and after treatment as well as at time of relapse.

During tumor remission Tumor M2-PK levels decreased significantly under treatment (P=0.0004). As might be expected, pre- and post-treatment marker concentrations did not differ significantly in patients with stable disease. In progressive lung cancer patients a significant increase in Tumor M2-PK was detectable (P=0.0094). Overall, a decrease of Tumor M2-PK was seen in 17 (89%) of all responders, while an increase could be detected in 16 (80%) of the patients experiencing tumor progression.

After treatment tumor relapse occurred in 30 patients. Tumor M2-PK increased significantly (P=0.0201) at time of relapse in 17 patients with non-small cell lung cancers and exceeded the cut-off in 11 of the 17 (65%).

In conclusion, Tumor M2-PK proved useful as a diagnostic aid for therapy control in lung cancer patients. This marker can also be used to detect tumor relapse after treatment. Tumor M2-PK could be well suited to complete the present diagnostic panel for monitoring of inoperable lung cancer patients.

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.

Section snippets

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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