Abstract
This study investigated the use of cell-cycle regulators for predicting progression of silent pituitary adenoma (SPA) after surgical resection via immunohistochemical analysis of tumor samples obtained by surgical resection. We reviewed the medical records of patients diagnosed with SPA from January 2000 to December 2013 in our institute. Immunohistochemical staining was performed on sections of the archived, paraffin-embedded tissues obtained by surgery; cell-cycle regulatory proteins p16, p15, p21, CDK 4 and 6, pRB protein, and cyclin D1; MIB-1 antigen; and p53. The primary end-point was to investigate the expression of cell-cycle regulatory proteins in SPA. The secondary end-point was to estimate the progression-free survival of SPA after surgical resection and find out its association with the expression of cell-cycle regulatory protein. Of the 127 SPA samples, 44 (34.6%) were from patients with progression during a mean follow-up period of 62.4 months (range 24.2–118.9 months). Immunohistochemistry (IHC) was reactive in 61 samples (48.0%) for p16, in 38 samples (29.9%) for p15, in 19 samples (15.0%) for p21, in 49 samples (38.6%) for CDK4, in 17 samples (13.4%) for CDK6, in 57 samples (44.9%) for pRB protein, and in 65 samples (51.2%) for cyclin D1. Multivariate analysis using a Cox proportional hazard regression model showed that null cell adenoma (95% confidence interval [CI] 0.276–0.808); somatotroph SPAs (95% CI, 1.296–3.121); corticotroph SPAs (95% CI 1.811–4.078); pluripotent SPAs (95% CI 2.264–5.194); immunohistochemical normostaining for p16 (95% CI 2.724–5.588); immunohistochemical overstaining for pRB protein (95% CI 2.557–5.333), cyclin D1 (95% CI 1.894–4.122), or MIB-1 (95% CI 1.561–4.133); mitotic index (95% CI 1.228-4.079); p53 (95% CI 1.307-4.065); and invasion into the cavernous sinus (95% CI 3.842–7.502) predicted SPA progression after surgical resection. Our study suggested that specific cell-cycle regulators were associated with SPA progression.
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