The periphery of pituitary macroadenoma expressed higher invasive capability: the importance of clinical implication

Partial resection of pituitary neuroendocrine tumor often results in residual tumor that increases the risk of recurrence. This pilot study aimed to determine whether the center and periphery of pituitary macroadenomas expressed different levels of biomarkers of invasiveness.

This prospective pilot study included 30 patients with newly diagnosed pituitary macroadenomas (≥ 10 mm) who underwent transsphenoidal surgery (2012-2013). Patients were randomly assigned to the sorted group (n = 15), where central and peripheral tumor zones were separately resected, or the unsorted group (n = 15), where tumors were resected without zonal distinction. Immunohistochemistry (IHC) quantified Ki-67, HIF-1α, CD31, CD34, CD105, and VEGF expression. Differences in biomarker expression across tumor zones, Knosp grade, and functional status were analyzed using the Wilcoxon signed-rank test and other statistical methods.

In the sorted group, the peripheral zone exhibited significantly higher immunoreactivities of Ki-67, HIF-1α, CD34, and VEGF (all p < 0.01) compared to the central zone, while CD31 and CD105 showed no significant differences. Subgroup analysis showed that in Knosp grade 0-2 tumors, CD34 and VEGF were elevated in the peripheral zone, whereas in Knosp grade 3-4 tumors, Ki-67, HIF-1α, and CD34 were significantly higher (all p < 0.05). In functioning adenomas, HIF-1α and CD34 were increased in the peripheral zone, while in non-functioning adenomas, Ki-67, HIF-1α, CD34, and VEGF were significantly elevated.

This pilot study revealed that biomarkers of invasiveness are expressed at higher levels in the peripheral zone of pituitary macroadenomas. Larger studies are needed to confirm these findings and evaluate their clinical significance.