Impact of delayed fixation on evaluation of cell proliferation in intracranial malignant tumors

Proliferative activity at tissue level, usually measured by mitotic count a nd immunohistochemical positive values by using anti-Ki-67 antibody, has be en shown to be of prognostic significance in many tumors. However, the impa ct of delayed fixation on these parameters is not clear. Some studies repor ted a decrease in mitotic activity caused by delayed fixation, whereas othe rs showed that the total number of mitotic figures remain unchanged. Most o f these studies have been performed on experimental tumors; the only two re ports that dealt with human cancer included a limited number of cases only. The aim of this study was to investigate the influence of delayed fixation on mitotic activity, evaluated with mitotic count (MC) and mitotic index ( MI), and on Ki-67 labeling index in human neoplastic tissue. Twenty intracr anial neoplasms were studied. These were fixed immediately after their remo val and after a fixation delay of 3 and 12 hours, respectively. The mean va lue for the variation of the MC was 95% and 76% for 3 and 12 hours, respect ively, of delayed fixation; the values for MI were similar: 91% and 73% for 3 and 12 hours, respectively, of delayed fixation. Ki-67 labeling index me an value was 90% both for 3 and 12 hours. All data were analyzed with the l inear regression test, which demonstrated that high correspondence does exi st between MC and MI and between MC and Ki-67 at the time of fixation (MC-M I, r = 0.93; MC-Ki-67, r := 0.59), but even after 12 hours of delay (MC-MI, r = 0.79; MC-Ki-67, r = 0.50); moreover the high correspondence was statis tically significant at p < 0.05 both at the time of fixation and at 12 hour s of delay. Our data seem to suggest that fixation delay does not affect ce ll proliferation.