The Prognostic Roles of the Ki-67 Proliferation Index, P53 Expression, Mitotic Index, and Radiological Tumor Invasion in Pituitary Adenomas

Abstract

The fourth edition of the World Health Organization (WHO) classification of pituitary tumors recommended evaluation of tumor proliferation and invasion to identify aggressiveness. We aimed to assess the prognostic roles of the Ki-67 proliferation index, mitotic index, P53 expression, and cavernous sinus invasion in pituitary adenomas (PAs). Among the 601 patients who underwent transnasal/transsphenoidal adenomectomy from 2001 to 2016, 101 patients (16.8%) who had tumors with a high (≥ 3%) Ki-67 index (group A) and a control group consisting of 43 patients with a low (< 3%) Ki 67 index who were matched for age, gender, and tumor type were included. Mitotic index and P53 expressions were evaluated. Patient characteristics, histopathology reports, pre/postoperative magnetic resonance imaging (MRI), and follow-up data were assessed retrospectively. The frequency of macroadenomas and mean tumor size were greater in group A when compared to group B (67.4 vs. 94.1%, p< 0.01 and 25 ± 10.6 vs. 18 ± 11 mm, p< 0.01, respectively). Invasion to cavernous sinus was found in 53 (36.8%) patients and was more frequent in group A (p<0.01). The mean number of surgery was higher in group A than group B (p< 0.05). The mean follow-up period was 46.6 ± 34 months. The postoperative MRIs and follow-up data for at least 24 months were available in 117 patients. Recurrence risk was higher in group A than group B (p = 0.03). Tumors with high Ki-67 proliferation index were grouped as 3–5, 6–10, 11–15, and > 15%. The risk of recurrence was not different between groups of high Ki-67 index. The optimal cutoff point of the Ki-67 proliferation index that predicted recurrence was 2.5% with 84.6% sensitivity and 47.4% specificity. The cavernous sinus invasion on MRI was associated with recurrence (p = 0.03). Tumor size and recurrence risk were not associated with P53 expression. High P53 expression was related with cavernous sinus invasion (p = 0.03). The mitotic index was not associated with recurrence risk and tumor invasion. Recurrence risk was higher in tumors with ≥ 2 histopathological atypia criteria (p = 0.01). High Ki-67 index with a 2.5% cutoff point and cavernous sinus invasion on MRI are reliable markers for predicting recurrence in PAs. Recurrence risk is also higher in tumors with two histopathological aggressiveness criteria. Strict follow-up and more aggressive treatment approaches may be necessary for invasive-proliferative PAs.

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