Immunohistochemical Study of NR2C2, BTG2, TBX19, and CDK2 Expression in 31 Paired Primary/Recurrent Nonfunctioning Pituitary Adenomas

Abstract

This study investigated potential markers for predicting nonfunctioning pituitary adenoma (NFPA) invasion and recurrence by high-throughput tissue microarray analyses. We retrospectively studied two groups of patients: 60 nonrecurrent NFPA cases that included noninvasion and invasion subtypes and 43 recurrent cases that included primary NFPA. A total of 31 paired patient samples were evaluated (12 patients with one surgery and 31 who had undergone two operations, with both tumors analyzed). Expressions of nuclear receptor subfamily 2 group C member 2 (NR2C2), B cell translocation gene 2, T-box-19 (TBX19), and cyclin-dependent kinase 2 (CDK2) in surgically resected specimens were assessed by immunohistochemistry. The relationships between marker expression and clinical characteristics including age, sex, tumor volume, and follow-up time were analyzed. Tumor volume and invasion as well as follow-up time were significantly associated with invasion and recurrence (P < 0.01). Of the 60 nonrecurrent samples, 15/41 and 13/19 showed high NR2C2 expression in the noninvasion and invasion groups, respectively (χ ² =5.287, P = 0.021). NR2C2 was also overexpressed in 43 primary recurrent cases (χ ² =5.433, P = 0.02), whereas CDK2 (χ ² = 11.242, P = 0.001) and TBX19 (χ ² = 4.875, P = 0.027) were downregulated. In the 31 paired samples, NR2C2 was more highly expressed in the recurrent as compared to the primary tumor. High NR2C2 expression was associated with NFPA invasion, recurrence, and progression, while TBX19 and CDK2 were associated with NFPA recurrence.

Figure 1

NR2C2 expressed in each group. (Aa): lowly expressed in noninvasive group; (Ab): highly expressed in invasive group; (Ba): lowly expressed in nonrecurrent group; (Bb): highly expressed in primary recurrent group; (Ca): lowly expressed in primary group; (Cb): highly expressed in recurrent group.

Figure 2

BTG2 and CDK2 expressed in each group. (Aa): BTG2 highly expressed in primary recurrent group; (Ab): BTG2 lowly expressed in nonrecurrent group. (Ba): CDK2 highly expressed in primary recurrent group; (Bb): CDK2 lowly expressed in nonrecurrent group.