LACK OF CORRELATION BETWEEN FLOW CYTOMETRIC AND IMMUNOHISTOLOGIC PROLIFERATION MEASUREMENTS OF TUMORS

We compared different means of assaying tumor proliferative activity b y either now cytometric or immunohistologic methods in formalin-fixed, part affin-embedded blocks. A series of 84 Dukes' stage B colorectal carcinomas were examined to identify high-risk patients who may potent ially benefit from adjuvant therapy. Flow cytometric analysis was perf ormed by a modified Hedley method with a combined S+G2/M phase prolife rative fraction calculated by means of a rectangular model after debri s subtraction. Immunohistologic tumor proliferative activity was analy zed by means of serial step sections from the same blocks used for Bow cytometric examination with antibodies to poliferating cell nuclear a ntigen (PCNA) and Ki-67 (MLB-1). Mean with standard deviation and (ran ge) tumor proliferative-activity measurements were: now cytometric ana lysis proliferative fraction = 14.8% +/- 5.3 (5-27%), PCNA = 43.2% +/- 21.2 (4-90%), and MIB-1 = 16.2% +/- 10.8 (2-47%). No correlation was found between dow cytometric proliferative fraction and immunohistolog ic tumor proliferation measurement or between PCNA and MIB-1 staining indices. Lack of correlation between now cytometric and immunohistolog ic findings maybe related to the use of archival formalin-fixed paraff in-embedded tissue for flow cytometric evaluation, with resultant incr eased debris and decreased accuracy of cell cycle calculations. Discor dance between PCNA and MIB-1 may reflect inherent problems with anti-P CNA antibody staining of formalin-fixed tissues whereby anti-PCNA clon e PC-10 detects non-replicon associated PCNA in formalin-fixed tissues . Prospective studies using fresh tissue with two-color multiparameter flow cytometric analysis and histogram-dependent background fitting m ay help to clarify the relationship between findings of turner prolife ration as analyzed by flow cytometric and by immunohistologic techniqu es.