Ki-67 and Proliferating Cell Nuclear Antigen Tumor Proliferative Indices in DNA Diploid Colorectal Adenocarcinomas:Correlation With Histopathologic Characteristics and Cell Cycle Analysis With Two-Color DNA Flow Cytometry

Abstract

The prognostic significance of tumor proliferative activity (TPA) in colorectal adenocarcinomas (CA) determined by proliferating cell nuclear antigen (PCNA) and Ki-67 staining is not well defined. Previous investigations of TPA using Ki-67 immunohistologic studies and flow cytometric (FCM) analysis have found no correlation with conventional histopathologic parameters. To better define the relationship of these various TPA measurements in CA, the authors selected 46 tumors with diploid DNA content previously analyzed by two-color DNA FCM analysis of fresh specimens to more effectively assess actual S-phase fractions (SPFs) from cytokeratin-gated DNA histograms for comparison with the following: (1) immunohistologic Ki-67 and PCNA tumor proliferation indices (TPIs); and (2) conventional histopathologic observations of prognostic import. These data show no significant correlation coefficient between Ki-67 or PCNA TPIs and SPFs derived from FCM analysis; however, the DNA diploid tumor subset categorized as having a greater than median SPF value had a significantly higher mean Ki-67 but not PCNA proliferation index. There was no correlation of any measure of proliferation with any of the eight histopathologic features of known prognostic significance.