THE VALUE OF CYTOMETRIC DNA ANALYSIS AS A PROGNOSTIC TOOL IN NEUROENDOCRINE NEOPLASTIC DISEASES

In several traditionally non-endocrine, common, human, neoplastic dise ases, it has become well established during the last few years, that c ytometric analyses of the DNA distribution pattern of the nuclei of tu mour cells can be an excellent supplement to the conventional prognost ic tools, (such as clinical staging and histopathologic malignancy ass essments). When analogous studies of the value of DNA analysis by mean s of flow cytometry and/or image cytometry are made in neuroendocrine (NEI neoplastic diseases, the ensuing results often become rather disa ppointing. Thus, clear-cut aneuploid DNA histograms can be found in th e neoplastic cell nuclei of clinically and histopathologically complet ely benign NE adenomas (and even hyperplastic nodules). In contrast, h ighly aggressive NE carcinomas not seldom reveal themselves to be comp osed 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, adeno mas of the anterior pituitary gland parathyroid adenomas, medullary ca rcinoma 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lower in NE tumours than i n most of the traditionally non-endocrine carcinomas and sarcomas Data from published and unpublished series of these Kinds of NE tumours, a nd those of prostatic and breast carcinomas with NE differentiation, a re given.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 typ e; By the same technique, it can be shown that in the pathogenesis of the hyergastrinaemia-induced ECL-cell carcinoids of the stomach, a swi tch from an euploid to an aneuploid nuclear DNA distribution pattern o ccurs in the ECL-cells when they pass from a state of hyperplasia to t hat of a genuine neoplasia. In neuroblastomas, a triploid (i.e. aneupl oid) DNA pattern is part of an algorithm capable of predicting a 96% s urvival rate, whereas a diploid/tetraploid (i.e. euploid) DNA pattern predicts a 0% survival.