The Value of Cytometric DNA Analysis as a Prognostic Tool in Neuroendocrine Neoplastic Diseases

Abstract

In several traditionally non-endocrine, common, human, neoplastic diseases, it has become well established during the last few years, that cytometric analyses of the DNA distribution pattern of the nuclei of tumour cells can be an excellent supplement to the conventional prognostic tools, (such as clinical staging and histopathologic malignancy assessments). When analogous studies of the value of DNA analysis by means of flow cytometry and/or image cytometry are made in neuroendocrine (NE) neoplastic diseases, the ensuing results often become rather disappointing. Thus, clear-cut aneuploid DNA histograms can be found in the neoplastic cell nuclei of clinically and histopathologically completely benign NE adenomas (and even hyperplastic nodules). In contrast, highly aggressive NE carcinomas not seldom reveal themselves to be composed of tumour cells with nuclei, displaying an euploid, i.e. normal, DNA pattern. Statements of this kind have been based on the results of comprehensive investigations in several laboratories, analysing such NE tumours as insulomas/insular carcinomas, bronchial/gastrointestinal carcinoids, phaeochromocytomas, paragangliomas, neuroblastomas, adenomas of the anterior pituitary gland, parathyroid adenomas, medullary carcinoma of the thyroid and Merkel-cell tumours of the skin. Thus, the prognostic value of the cytometric DNA ploidy pattern of the nuclei of neoplastic parenchymal cells is definitely lower in NE tumours than in most of the traditionally non-endocrine carcinomas and sarcomas. Data from published and unpublished series of these kinds of NE tumours, and those of prostatic and breast carcinomas with NE differentiation, are given. By means of a new, consecutive double staining technique, it was shown that in idiopathic nesidioblastosis, the hyperinsulinism is caused by beta cells with a nuclear DNA ploidy pattern of euploid type. By the same technique, it can be shown that in the pathogenesis of the hypergastrinaemia-induced ECL-cell carcinoids of the stomach, a switch from an euploid to an aneuploid nuclear DNA distribution pattern occurs in the ECL-cells when they pass from a state of hyperplasia to that of a genuine neoplasia. In neuroblastomas, a triploid (i.e. aneuploid) DNA pattern is part of an algorithm capable of predicting a 96% survival rate, whereas a diploid/tetraploid (i.e. euploid) DNA pattern predicts a 0% survival.