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Updated: Jan 3, 2026

Two-dimensional Gel Electrophoresis Coupled with Mass Spectrometry Methods for an Analysis of Human Pituitary Adenoma Tissue Proteome
Published on: April 2, 2018
Predicting short-term recurrence in pituitary adenomas: Phosphohistone-H3 (Ser 10) proves an effective biomarker
Aims:
This research sought to assess the effectiveness of the phosphohistone-H3 (PHH3) mitotic index (MI) as a biomarker to predict early recurrence and inform treatment options and follow-up intervals.
Materials And Methods:
Quantitative immunohistochemical analysis was performed to assess H & E, PHH3, and MIB-1/Ki-67 expression in samples of 141 PAs. Next, the correlation between mitotic figures on H & E (mitotic figures), PHH3 MI, Ki-67 labeling index (LI) and clinical variables was analyzed. The difference among primary- and repeated-surgery groups, nonrecurrent and recurrent groups, and tumor subtypes of PHH3 MI and Ki-67 LI were also assessed. Finally, survival analysis was performed to test the predictive capacity of the biomarkers.
Results:
The results showed that the group with Ki-67 LI > 2.6% was more prone to short-term recurrence (p < 0.05). Ki-67 LI also correlated with tumor size and Knosp grades (p < 0.05); Ki-67 LI was higher in PAs with Knosp grades III and IV. However, PHH3-positive tumor cells were strongly correlated with the mitosis observed by hematoxylin-eosin staining. Significantly, the PHH3 MI showed stronger short-term prognostic capacity than Ki-67 LI. With a cut-off value of 0.5%, PHH3 MI predicted recurrence with a sensitivity and specificity of 61.5 and 92.1%, respectively. Multivariate survival analysis found that only PHH3 MI was found to be an independent prognostic factor with a hazard ratio of 2.884, compared with 1.076 for Ki-67 LI.
Conclusion:
Phosphohistone-H3 is shown to be an effective prognostic biomarker for short-term recurrence of PAs. This suggests that it should be used alongside Ki-67 as a predictor for prognosis.

