Cyclin D1 (CCND1) genotype is associated with tumour grade in sporadic pituitary adenomas

The cyclin D1 (CCND1) gene contains a frequent A/G polymorphism within the splice donor region of exon 4/intron 4. CCND1 genotype is associated with c linical outcome in a number of malignancies although prognostic significanc e varies with tumour type. We examined CCND1 allele frequencies and genotyp e distribution in 294 patients with sporadic pituitary adenomas of various histologies. CCND1 allele frequencies and distribution of genotypes were si milar in the 294 cases compared with previously reported control population s. Analysis according to tumour subtype showed no statistical difference in allele frequencies compared with controls. However, CCND1 genotype distrib ution in the somatotrophinomas showed a significant difference compared wit h normal controls (P = 0.008). We next examined CCND1 allele frequencies an d genotype distribution across the tumour grades. Within the total tumour c ohort the CCND1 allele frequencies showed a significant inverse relationshi p across the tumour grades (P = 0.005). The CCND1 A allele progressively in creased from grade 1 (0.37) through to grade 4 (0.62) tumours, whilst the C CND1 G allele frequency progressively decreased from grade 1 (0.63) through to grade 4 (0.38) tumours. Trend analysis of CCND1 genotypes showed a sign ificant progressive increase in AA frequency from grade 1 (15%) through to grade 4 (46%) tumours (P = 0.005). The CCND1 GG genotype progressively decr eased from grade 1 (41 %) through to grade 4 (23 %) tumours (P = 0.204). No statistical significance was observed between CCND1 AG genotype and tumour grades. While the functional significance of the observed segregation of t he CCND1 A/G polymorphism and tumour grade is unclear, our data suggest tha t CCND1 allele frequencies and genotype distributions show significant diff erences between tumour grades in sporadic pituitary adenomas. Since CCND1 g enotype may be determined by analysis of peripheral blood samples it may pr ovide a useful predictive marker for those turnours likely to show invasive behaviour. This may be clinically useful in indicating which tumours shoul d receive adjunctive treatment (e.g. radiotherapy) immediately after surgic al resection.