Flow Cytometric Evaluation of Proliferating Cell Nuclear Antigen Expression in Human Hematopoietic Malignancies

Abstract

Cell proliferation is a strong prognostic factor in various malignancies including non-Hodgkin's lymphoma's (NHL). Several methods to evaluate tumour proliferation are available based on immunohistochemical and flow cytometric techniques, but none has been widely accepted for multicenter studies. In the present study 51 samples from patients with haematological disorders were analysed for the expression of proliferating cell nuclear antigen (PCNA) by a previously described flow cytometric approach. S-phase specific PCNA (PCNA-S) as well as growth fraction-associated PCNA (PCNA-tot) expression were evaluated. The mean value for PCNA-S was 9.0% and for PCNA-tot 17,4%. PCNA-S and PCNA-tot correlated strongly to each other (r s = 0.969, p < 0.001) and to the S-phase fraction determined by DNA histogram analysis (r_s = 0.927 and 0.934 respectively, p < 0.001). In 23 cases with NHL in vivo iododeoxyuridine (IdUrd) labelling was performed to assess the labelling index (IdUrd-LI, i.e. S-phase fraction), S-phase duration time (Ts) and potential tumour doubling time (Tpot). IdUrd-Li correlated significantly to both PCNA-S and PCNA-tot (r_s = 0.704 and 0.622 respectively, p < 0.001 and 0.02). In conclusion, especially the PCNA-S seemed to be a candidate for future larger studies of proliferation related aspects of haematological malignancies.