J Pathol Transl Med.  2022 Jan;56(1):22-31. 10.4132/jptm.2021.08.31.

Association of PTTG1 expression with invasiveness of non-functioning pituitary adenomas

• Kum SJ
• Lee HW
• Kim SG
• Park H
• Hwang I
• Kim SP

• KMID: 2524226
• DOI: http://doi.org/10.4132/jptm.2021.08.31

Abstract

Background
Pituitary tumor transforming gene 1 (PTTG1), paired-like homeodomain 2 (PITX2), and galectin-3 have been widely studied as predictive biomarkers for various tumors and are involved in tumorigenesis and tumor progression. We evaluated the usefulness of PTTG1, PITX2, and galectin-3 as predictive biomarkers for invasive non-functioning pituitary adenomas (NFPAs) by determining the relationship between the expressions of these three proteins and the invasiveness of the NFPAs. We also investigated whether PTTG1, E-cadherin, and Ki-67, which are known to be related to each other, show a correlation with NFPA features.
Methods
A retrospective study was conducted on 87 patients with NPFAs who underwent surgical removal. The NFPAs were classified into three groups based on magnetic resonance imaging findings of suprasellar extension and cavernous sinus invasion. Immunohistochemical staining for PTTG1, PITX2, galectin-3, E-cadherin, and Ki-67 was performed on tissue microarrays.
Results
PTTG1 expression showed a statistically significant correlation with the invasiveness of NFPAs, whereas PITX2 and galectin-3 did not have a relationship with the invasiveness of NFPAs. Moreover, there was no association among PTTG1, E-cadherin, and Ki-67 expression.
Conclusions
PTTG1 has the potential to serve as a predictive biomarker for invasive NFPA. Furthermore, this study may serve as a reference for the development of PTTG1-targeted therapeutic agents.

Keyword

Non-functioning pituitary adenomas; Pituitary tumor transforming gene expression; Invasiveness

Figure

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  Fig. 1 Invasiveness groups of non-functioning pituitary adenoma (NFPA) based on suprasellar extension (SSE) and cavernous sinus invasion (CSI) on magnetic resonance imaging (MRI). The representative MRI images of SSE (arrows) and CSI (arrowheads) are shown. NFPAs were classified into three groups based on the MRI findings: group I, neither SSE nor CSI; group II, only one of SSE or CSI; group III, both SSE and CSI.

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  Fig. 2 Scoring of immunohistochemical staining for pituitary tumor transforming gene (PTTG1), paired-like homeodomain 2 (PITX2), and galectin-3. The intensity of immunohistochemical stains was scored from 0 (negative) to 3 (strong). PTTG1: a score of 0 was regarded as negative, scores of 1 and 2 were regarded as low, and a score of 3 was regarded as high expression. PITX2 and galectin-3: a score of 0 was regarded as negative, a score of 1 was regarded as low, and scores of 2 and 3 were regarded as high expression.

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  Fig. 3 Stacked column chart showing the ratio of pituitary tumor transforming gene (PTTG1) expression in each invasiveness group. As the level of invasiveness increased, the proportion of high PTTG1 expression tended to increase.

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  Fig. 4 Scoring of immunohistochemical staining for E-cadherin and Ki-67. E-cadherin: a score of 0 was regarded as negative, and scores of 1 to 3 were regarded as positive expression. Ki-67 index was measured by image analyzer, and two samples of the stain are shown.

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  Fig. 5 Box plots of the distribution of the tumor size by invasion group and recurrence. A larger tumor size was associated with higher invasiveness (A) and a higher recurrence rate (B).

Reference

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