Introduction: Abnormalities in cell cycle pathways, such as CDKN1B (p27) underexpression, have been identified in the pathogenesis of pituitary adenomas, but their underlying mechanisms have not been elucidated. Ribosomal proteins have been recently related to pituitary tumorigenesis. In gastric cancer, RPS13 down-regulates p27 and promotes cell cycle progression; these mechanisms have not yet been explored in pituitary adenomas.
Objective: To evaluate the relationship between RPS13 and CDKN1B, CDK2, CCNE1, MYC gene expression in pituitary tumorigenesis and its association to clinical findings.
Methods: We studied four groups: non-functioning pituitary adenomas (NFPA, n=21), GH-secreting adenomas (n=18), ACTH-secreting adenomas (n=12) and normal pituitaries (n=07). Clinical and pathological data were collected. RNA was isolated by TRIzol method. Gene expression was assessed by qRT-PCR. KruskalWallis test was used for continuous variables between groups and Fisher Exact test for categorical data.
Results: Differential gene expression among the groups were observed in CDKN1B (P=0.03), CCNE1 (P=0.02) and MYC (P=0.002), but not RPS13 (P=0.1) and CDK2 (P=0.07). We observed CDKN1B underexpression in somatotrophinomas, CCNE1 overexpression in NFPA and MYC underexpression in NFPA. In corticotrophinomas, we found no association between gene expression and tumor size, remission or immunohistochemistry (IHC). In somatotrophinomas, no relationship was found between gene expression and tumor size, visual field, IGF-1 levels, basal and post-oGTT GH levels, IHC, post-surgery remission and disease control. Tumors with higher CDKN1B expression tended to achieve control with somatostatin agonist (P=0.08). In NFPA, higher CDK2 expression was associated to null cell subtype (P=0.03) with a tendency to correlate with tumor size (P=0.08). Higher CCNE1 expression was associated with remission (P=0.02).
Conclusion: The p27-CDK2-CCNE1 pathway seems dysregulated in pituitary adenomas and may interact with other aberrant pathways, leading to an environment that may have putative role in pituitary tumorigenesis. Overexpression of RPS13, however, does not seem to be the underlying mechanism.
27 Apr - 01 May 2013
European Society of Endocrinology