In 6 patients with breast cancer – of whom specimens of the primary tumor as well as one of its metastases were available for examination – we demonstrated intratumoral and intertumoral heterogeneity in expression of activity of the glycolytic enzymes hexokinase, phosphofructokinase, aldolase, enolase and pyruvate kinase. Heterogeneity also existed in isozyme composition of pyruvate kinase. The transition of the tumors towards normal surrounding breast tissue showed either a sharp drop in activity, or a gradual decrease in activity, corresponding to pushing margins or infiltrative growth of the tumor as was demonstrated by histologic examination of these specimens. Likewise, the shift towards expression of K isozyme of pyruvate kinase in breast cancer compared to normal breast tissue could be demonstrated.
The cellular expression of K‐type pyruvate kinase was studied immunohistochemically in several normal and neoplastic tissues of human origin. The authors used the monoclonal antibody, designated as ES1, which was raised against human K‐type pyruvate kinase. In contrast to the normal counterparts, a strong immunoreactivity was found in a rhabdomyosarcoma (n = 1), in a carcinoma of the pancreas (n = 1), and in neurofibromas (n = 2). Furthermore, the staining in leiomyosarcomas (n = 2) was shown to be more intense when compared with both normal smooth muscle cells and leiomyomas (n = 2). These findings show that knowledge about the cellular expression of the K‐type pyruvate kinase identifies cell types for which its expression serves as oncodevelopmental marker. In addition, these immunohistochemical studies give information whether shifts toward K‐type containing isozymes of pyruvate kinase, which are determined by electrophoresis in whole cytosolic extracts of various tumors, are due to an altered gene expression or due to proliferation of cells which normally express already the K‐type pyruvate kinase. The first possibility probably occurs in rhabdomyosarcomas. The latter possibility seems to be valid for astrocytomas because astrocytes express the K‐type pyruvate kinase in normal brain. Cancer 68:2595–2601, 1991.
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