Flow cytometric DNA ploidy and cells phase fractions in recurrent human pituitary adenomas. A correlative study of flow cytometric analysis and the expression of proliferating cell nuclear antigen

Flow cytometric analysis was applied to embedded tissue to measure the proliferative activity and the DNA ploidy of 16 recurrent and 17 nonrecurrent pituitary adenomas. The results were compared with data from a previous study which demonstrated that proliferating cell nuclear antigen (PCNA) labeling index was higher in recurrent adenomas than in nonrecurrent adenomas. Flow cytometric analysis as a tool for predicting aggressive behavior has been useful in a variety of human tumors; however, its prognostic value in pituitary adenomas is controversial. Therefore, we decided to explore the relationship of the results of flow cytometry and proliferating cell nuclear antigen labeling indices with the prognosis of pituitary adenomas. Three out of 16 recurrent adenomas and five out of 17 nonrecurrent adenomas demonstrated a DNA aneuploid pattern. All the nonfunctional recurrent adenomas had a diploid pattern, while only 40% of the functional recurrent adenomas had a diploid pattern. The G0/G1 phase fraction was higher in the recurrent adenomas, than in the nonrecurrent ones (p = 0.0005). In contrast, the S-phase fraction and the coefficient of variation were higher in the nonrecurrent adenomas (5.9 ± 1.0%, 7.0 ± 0.75, respectively) than in the recurrent ones (2.5 ± 0.6%, 4.0 ± 0.2%, respectively) (p = 0.003 and p = 0.001, respectively). The proliferating cell nuclear antigen labeling indices were higher in the recurrent adenomas (18.9 ± 4.5%) than in the nonrecurrent adenomas (2.6 ± 1.6%) (p = 0.003). The S-phase of flow cytometry correlated weakly with the proliferating cell nuclear antigen labeling indices when the recurrent and the nonrecurrent adenomas were considered as one group. (r = -0.356, p = 0.033) But no significant correlations were observed when the groups of recurrent (r = -0.311, p = 0.195) and nonrecurrent tumors (r = -0.019, p = 0.942) were compared separately. The results of flow cytometric analysis suggest that recurrent adenomas may have a higher proportion of cells in the presynthetic phase than the nonrecurrent adenomas. This study suggests that flow cytometric analysis is of limited value in predicting recurrence of pituitary adenomas.