SIGNIFICANCE OF PROLIFERATING CELL NUCLEAR ANTIGEN INDEX IN PREDICTING PITUITARY-ADENOMA RECURRENCE

The recurrence rate of pituitary adenomas has been reported to be as h igh as 10% to 35% despite their generally benign nature. A monoclonal antibody directed against proliferating cell nuclear antigen (PCNA) wa s used to investigate whether the proliferative index might help to pr edict adenoma recurrence. This antigen is a nuclear protein identified as the auxiliary protein of deoxyribonucleic acid polymerase delta, a nd its gene expression correlates with cell proliferation. The authors studied 30 patients with recurrent pituitary adenomas, 32 with nonrec urrent adenomas, and seven normal pituitary tissue samples. The mean i nterval to recurrence (+/- standard error of the mean) was 5.3 +/- 0.7 years. The age- and sex-matched nonrecurrent group had a mean follow- up period of 6.6 +/- 0.3 years without clinical recurrence. Mean perce ntages of PCNA-positive tumor nuclei in both the initial and the secon d surgical specimens of the recurrent adenomas (13.45% +/- 3.02% and 1 9.56% +/- 3.66%, respectively) were significantly higher than that of the nonrecurrent group (2.49% +/- 1.21%). In addition, recurrent tumor s had a higher PCNA index than the initial tumors in the same patients . Normal anterior pituitary gland tissue had a significantly lower mea n PCNA index (0.12% +/- 0.11%) than either patient group. Stepwise mul tivariate regression analysis indicated that factors which collectivel y cor-related significantly with recurrence were: high PCNA index, lar ge tumor size, extrasellar extension, and incomplete surgical excision . The PCNA nuclear count was not associated with age, sex, or hormone hypersecretion, but was higher in macro- than in microadenomas, in tum ors with extrasellar extension, and in those incompletely excised. A h igher PCNA index also correlated with a shorter disease-free interval. The authors conclude that evaluation of the PCNA index assists in pre dicting the likelihood of pituitary adenoma recurrence.