Cell proliferation, apoptosis, and angiogenesis in non-functional pituitary adenoma: association with tumor invasiveness.

PURPOSE

Non-functioning pituitary adenoma (NFPA) is the most prevalent pituitary macroadenoma. No prognostic marker has been found to explain the behavior of these tumors. We aimed to explore cell proliferation, apoptosis, proangiogenic markers, and microvascular density (MVD) in noninvasive and invasive NFPAs.

METHODS

Adenoma invasiveness was defined according to Knosp and Hardy classifications based on preoperative magnetic resonance imaging scans. Cell proliferation was examined using Ki67 and P53. Tissue expression of Bcl-2 was used to assess the antiapoptosis pathway. CD34 and CD105 were measured to evaluate MVD, while VEGF expression was assessed as an indicator of pro-angiogenesis. Moreover, VEGF, bFGF, endocan, and endostatin were measured on preoperative serum samples.

RESULTS

Tissue and serum markers were examined in 18 patients with invasive and 21 patients with noninvasive NFPAs. Ki67 less than 3% was reported in 10 invasive and 14 noninvasive NFPAs (P = 0.752). P53 staining was negative in all subjects. In addition, Bcl-2 staining was negative in 15 and 20 subjects, respectively (P = 0.718). VEGF-A expression 2+ or 3+ was reported in 9 invasive and 11 noninvasive macroadenomas (P = 0.83). Moreover, CD34 and CD105 positivity were comparable between the two groups. Furthermore, the comparison of serum markers showed no significant differences.

CONCLUSION

Cell proliferation, apoptosis, and angiogenesis play a limited role in NFPA behavior.