Differential pattern of DNA-Aneuploidy in human malignancies

The differential pattern of DNA-aneuploidy, detected by flow cytometry (FCM) regarding its frequency, grade and multiclonality, was investigated and correlated to tumor type, malignancy grade, tumor stage and prognosis in a multi-institutional study at the University of Münster. High resolution measurements using admixed normal blood reference cells were undertaken in 2413 cases of 13 different malignant diseases and in 776 benign lesions or samples. The incidence of DNA-aneuploidy was highest in melanomas, carcinomas, testicular tumors, sarcomas (75%–95%) and myelomas (65%). Acute leukemias showed an intermediate DNA-aneuploidy rate of 40% with special subgroups represented by common ALL (44%), p < 0.05) and myelomonocytic/monocytic AML (47%, p < 0.01). The lowest DNA-aneuploidy-rate was found in basal cell skin carcinomas (19%) and congenital melanocytic nevi (9%). No case of DNA-aneuploidy was observed in the 776 benign lesions or samples. — DNA-indices giving the grade of DNA-aneuploidy with 1.0 for normal diploid G 1/10 cells were found distributed predominantly between 1.0 and 2.0 in the solid tumors, except testicular tumors, clustering around a triploid maximum at 1.5. DNA-indices of myelomas and acute leukemias generally ranged below 1.25 with lower DNA-aneuploidy grades in AML than in ALL (p < 0.01). — In melanomas the aneuploidy rate was higher (86%) in metastases than in the primary tumors (54%, p = 0.001). DNA-aneuploidy incidence positively correlated to the thickness and surface area of the primary tumors (p = 0.001). Aneuploid resected primary melanomas showed metastases formation in 17% after 2 years vs. 6% in non-aneuploid cases (p = 0.05). In contrast, patients with aneuploid AML or ALL showed a tendency to longer remission duration. — We conclude that DNA-aneuploidy represents the most common malignancy-specific cell marker correlating with malignancy grade, tumor stage and prognosis in several aspects.