A COMPARISON OF PROLIFERATION MARKERS AND THEIR PROGNOSTIC VALUE FOR WOMEN WITH ENDOMETRIAL CARCINOMA - KI-67, PROLIFERATING CELL NUCLEAR ANTIGEN, AND FLOW CYTOMETRIC S-PHASE FRACTION

BACKGROUND. The understanding of proliferation is a central issue in o ncology. Several methods exist for the assessment of the growth fracti on and cell-cycle time, but comparative studies that give the clinicia n advice about the most reliable use of new markers are few. The aim o f the current study was to perform methodologic, descriptive, comparat ive, and prognostic studies of Ki-67, proliferating cell nuclear antig en (PCNA), and flow cytometric S-phase fraction (SPF) in endometrial c arcinoma. METHODS. The expression of Ki-57 (n = 175) acid PCNA (n = 14 6) were studied immunohistochemically, and the SPF (n = 297) by now cy tometry. The median follow-up time was 78 months. RESULTS. Neither Ki- 67 nor PCNA had any correlation to either the stage or the histopathol ogic subtype of the tumors, but they were covariant with. the histopat hologic grade (P < 0.05). There was an interrelationship between Ki-67 and PCNA (P < 0.001), and both were associated with the size of the S PF (P < 0.0001 and P < 0.05, respectively). Mean SPF was high in advan ced stages and strongly associated with histopathologic subtype (P < 0 .0001) and ploidy (P < 0.0001). Tumors with strong Ki-67 expression we re more often aneuploid (P < 0.01). In initial analyses, Ki-67 and SPF were predictors of poor survival (P < 0.05 and P < 0.001, respectivel y), whereas PCNA was not. When SPF was added to a comprehensive multiv ariate model, Ki-67 provided no further prognostic information, wherea s SPF remained a powerful predictor of survival. CONCLUSIONS. Ki-67 an d, to a lesser extent, PCNA, give approximate estimates of the growth fraction, whereas SPF only reflects the proportion of cells in S-phase . However, SPF is by far the strongest predictor of survival. (C) 1996 American Cancer Society.