Introduction: Prolactinomas are thought to arise from the proliferation of a mutated pituitary stem cell which is subjected to the growth stimuli of several permissive factors, although the pathogenetic mechanisms underlying the tumorigenesis still remain unclear. The present study aimed to investigate the role of p16 (540C→G and 580C→T) and MDM2 (SNP309T→G) gene polymorphisms in tumorigenesis and characteristics of prolactinoma.
Methods/Design: 74 patients with prolactinoma and age- and gender-matched healthy subjects were enrolled in the study. Serum prolactin levels were measured by enzyme linked immunosorbent assay. DNA was extracted from peripheral blood samples then p16 and MDM2 polymorphisms were determined by polymerase chain reaction-restriction fragment polymorphism and agarose gel electrophoresis.
Results: p16 540C→G genotype distribution was found as CC:66.2%, CG:28.4%, GG:5.4%; p16 580C→T genotype distribution was found as CC:82.4%, CT:17.6%, TT:0% and MDM2 genotype distribution was found as TT:31.1%, TG:47.3%, GG:21.6% in patients with prolactinoma. Tumor diameter before treatment was correlated with prolactin levels before treatment and percentage of prolactin decrease with treatment (P<0.001 r=0.719, P=0.034 r=0.256, respectively). Tumor diameter after treatment was correlated with prolactin levels (P<0.001 r=0.569). CC genotype (homozygote wild type) frequency is higher without statistical significance in both p16 540C→G and p16 580C→T polymorphisms among prolactinoma patients. The number of patients with tumor size decreased more than 50% in homozygous genotype (TT+GG) carriers of MDM2 SNP309T→G is significantly higher than in heterozygous genotype (TG) carriers (P=0.003, OR: 0.18, CI: 0.060.58).
Conclusion: This study showed that p16 and MDM2 polymorphisms do not play an important role in tumorigenesis, but some genotypes of these polymorphisms could be associated with follow-up characteristics of prolactinoma. Further studies are needed to clarify the underlying mechanisms of the tumorigenesis in order to define prognostic factors and facilitate appropriate treatment choices for patients with prolactinoma.