Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence

Abstract

The recurrence rate of pituitary adenomas has been reported to be as high as 10% to 35% despite their generally benign nature. A monoclonal antibody directed against proliferating cell nuclear antigen (PCNA) was used to investigate whether the proliferative index might help to predict adenoma recurrence. This antigen is a nuclear protein identified as the auxiliary protein of deoxyribonucleic acid polymerase delta, and its gene expression correlates with cell proliferation. The authors studied 30 patients with recurrent pituitary adenomas, 32 with nonrecurrent adenomas, and seven normal pituitary tissue samples. The mean interval 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 percentages of PCNA-positive tumor nuclei in both the initial and the second surgical specimens of the recurrent adenomas (13.45% +/- 3.02% and 19.56% +/- 3.66%, respectively) were significantly higher than that of the nonrecurrent group (2.49% +/- 1.21%). In addition, recurrent tumors had a higher PCNA index than the initial tumors in the same patients. Normal anterior pituitary gland tissue had a significantly lower mean PCNA index (0.12% +/- 0.11%) than either patient group. Stepwise multivariate regression analysis indicated that factors which collectively correlated significantly with recurrence were: high PCNA index, large 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 tumors with extrasellar extension, and in those incompletely excised. A higher PCNA index also correlated with a shorter disease-free interval. The authors conclude that evaluation of the PCNA index assists in predicting the likelihood of pituitary adenoma recurrence.

Relevance of Ki-67 and prognostic factors for recurrence/progression of gonadotropic adenomas after first surgery

“…However, there is some discrepancy in the literature with regard to the relapse rate and invasiveness of pituitary adenomas. Several authors have found a correlation between the Ki-67 LI and the relapse rate (9,22,(29)(30)(31)(32)(33)(34), while others have not (19,(35)(36)(37). However, most of these studies were heterogeneous, including different types of pituitary adenoma and various postoperative therapies.…”

“…As is commonly seen in other endocrine neoplasms, Ki-67-positive cells were heterogeneously distributed throughout the tumor. Following studies on proliferative activity in pituitary adenomas (22)(23)(24), we evaluated the Ki-67 LI in the areas of the tumor where Ki-67-labelled nuclei were predominant. Thus, immunostained sections were screened under the microscope, and the areas containing the greatest number of Ki-67-stained nuclei were outlined with a pencil, allowing easy localization during image analysis.…”

Mono- and plurihormonal thyrotropic pituitary adenomas: pathological, hormonal and clinical studies in 12 patients

“…These two markers are still being assessed. According to some authors (22), tumor size and PCNA immunoreactivity correlate. For others, Ki-67 is a more reliable marker, correlating well with proliferation potential and invasiveness (23)(24)(25).…”

Ki-67 Expression for Predicting Progression of Postoperative Residual Pituitary Adenomas: Correlations With Clinical Variables

“…8,18) Various attempts have been made to establish markers that correlate with the clinical behavior of pituitary adenomas, such as invasion, recurrence, or malignancy. 1,2,5,[7][8][9][10][12][13][14][15]17,[19][20][21][22][23][24][27][28][29][30][31][32][33] Among the available methods of growth fraction determination, Ki-67 is a reliable marker for growth fraction determination of various specific cell cycle antigens. 1,12,32) Ki-67 is a protein which reacts with a …”