MSH6/2 and PD-L1 Expressions Are Associated with Tumor Growth and Invasiveness in Silent Pituitary Adenoma Subtypes
Mismatch repair genes <i>mutS homologs 6/2</i> (<i>MSH6/2</i>) expressions are involved in tumor growth and <i>programmed cell death 1 ligand 1</i> (<i>PD-L1</i>) expression in tumor immunity, but the direct association with pituitary adenomas (PAs) is...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/8/2831 |
| Summary: | Mismatch repair genes <i>mutS homologs 6/2</i> (<i>MSH6/2</i>) expressions are involved in tumor growth and <i>programmed cell death 1 ligand 1</i> (<i>PD-L1</i>) expression in tumor immunity, but the direct association with pituitary adenomas (PAs) is not well understood. We aimed to clarify the effects of MSH6/2 and PD-L1 expression on tumor proliferation and invasiveness in nonfunctioning (NF) PAs. We performed immunohistochemistry to classify the NFPAs into gonadotroph adenoma (GAs), silent corticotroph adenomas (SCAs), null cell adenoma (NCAs), and pituitary transcription factor 1 (PIT1) lineage PAs. We evaluated <i>MSH6/2</i> and <i>PD-L1</i> mRNA expressions in NFPAs by real-time PCR (<i>n</i> = 73), and statistically analyzed the expressions and clinicopathological factors. We also investigated the effect of MSH6 knockout on PD-L1 expression in AtT-20ins and GH3. MSH6/2 expressions were significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. <i>MSH6/2</i> expressions were positively associated with <i>PD-L1</i> expression. <i>PD-L1</i> expression was significantly lower in invasive NFPAs than in non-invasive NFPAs, and lower in SCAs and NCAs than in GAs. Although <i>MSH6/2</i> expressions also tended to be lower in PIT1 lineage PAs than in GAs, PIT1 lineage PAs expressed <i>PD-L1</i> equivalently to GA, which was unlike SCAs and NCAs. MSH6 knockout in AtT-20ins and GH3 significantly decreased <i>PD-L1</i> expression (75% and 34% reduction, respectively) with cell proliferation promotion. In conclusion, differences in <i>MSH6/2</i> and <i>PD-L1</i> expressions of SCAs, NCAs, and PIT1-lineage PAs from those of GAs appear to contribute to their clinically aggressive characteristics, such as more proliferation and invasiveness. |
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| ISSN: | 1661-6596 1422-0067 |