Markers of proliferation and invasiveness in somatotropinomas

Introduction: In the search for markers of invasiveness of pituitary adenomas, we studied the expression of Ki-67 antigen, TOPO 2A (topoisomerase 2 alpha), AIP (Aryl Hydrocarbon Receptor-Interacting Protein), and VEGF (Vascular Endothelial Growth Factor) in somatotropinomas. Material and methods: We retrospectively studied a group of 31 patients who underwent pituitary tumour surgery. Expression of Ki-67, TOPO 2A, AIP, and VEGF in surgical specimens was determined by immunohistochemistry. Relations between quantitatively determined markers and clinical symptoms, tumour features, and MR imaging, were analysed. Acromegaly was confirmed by hormonal tests in all patients studied. Local invasiveness (cavernous sinus penetration, optic chiasm compression or suprasellar extension) was observed in 18/31 patients (58.1%). Results: Ki-67 was expressed in 77.4%, TOPO 2A in 87.1%, AIP in 83.8%, and VEGF in 87.1% of 31 cases of somatropinoma. Median values of Ki-67, TOPO 2A, AIP, and cytoplasmic VEGF indices, were 1.2% [IQR = 2.2], 1.5% [IQR = 1.6], 21.26% [IQR = 20.1], and 20.4% [IQR = 15.4], respectively. Ki-67, TOPO 2A, AIP, and VEGF expression was not correlated with age nor with patient gender (p > 0.05). Only Ki-67 and TOPO 2A correlated with tumour size (for Ki-67: r = 0.42, p = 0.025; for TOPO 2A: r = 0.53, p = 0.003). Ki-67 and TOPO 2A levels were significantly higher in invasive compared to noninvasive somatropinomas (Ki-67 mean values: 1.85 +/- 1.33% vs. 0.95 +/- 1.07%, p = 0.024; TOPO 2A mean values: 2.19 +/- 1.63% vs. 1.45 +/- 1.23%, p = 0.011). Conclusions: Ki-67, TOPO 2A, AIP, and VEGF were expressed in over 70% of all somatotropinomas. Only Ki-67 and TOPO 2A expression correlated with tumour size and tumour invasiveness.