Background: The cyclin D1 gene (CCND1) is a proto-oncogene playing a critical role in the transition through the G1 to the S phase of the cell cycle and is overexpressed in many tumors. G870A polymorphism at the exon4/intron4 splicing region of the CCND1 gene may play a role in pituitary tumorigenesis and invasiveness. The objective of this study was to examine CCND1 polymorphism in patients with different types of sporadic pituitary adenomas.
Material/methods: One hundred thirty patients (38 male, 92 female, mean age: 45.37+/-13.55 SD years) with sporadic pituitary adenomas (PA group) and 129 healthy controls (HC group) were included in the study. The CCND1 G870A polymorphism in PA and HC were genotyped by PCR-RFLP using peripheral blood samples. CCND1 expression was also evaluated with an immunohistochemical method in tumor tissues of 39 patients of the PA group.
Results: The genotype distribution in the PA [AA: 30 (23.1%), AG: 90 (69.2%), GG: 10 (7.7%)] was statistically different from the HC group [AA: 36 (27.9%), AG: 64 (49.6%), GG: 29 (22.5%), p=0.001]. Patients carrying the AG genotype were more frequent compared with the control group. Tumor type, volume, and invasion were not related to the genotype. Immunohistochemically, 21 of the 39 tumors showed nuclear positivity for CCND1, varying between 1 and 40% of tumor cells. Positive staining was observed more intense in patients carrying the AG genotype.
Conclusions: CCND1 polymorphism may be an early event in tumorigenesis, but it is not a reliable prognostic criterion.